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rs4820268 (1) rs10079250 (1) rs1799750 (1) rs9366637 (1) rs4148738 (1) rs10456542 (1) rs25648 (1) rs9984723 (1) rs766996587 (1) rs2398162 (1) rs7291050 (1) rs1011970 (1) rs4253728 (1) rs12143842 (1)

SNPMiner SNPMiner Trials (Home Page)


Report for SNP rs12979860

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 38 clinical trials

Clinical Trials


1 Randomised, Placebo-controlled, Multi-centre Study to Assess the Efficacy and Safety of Eltrombopag in Thrombocytopenic Subjects With Hepatitis C Virus (HCV) Infection Who Are Otherwise Eligible to Initiate Antiviral Therapy (Peginterferon Alfa-2a Plus Ribavirin

The purpose of this study is to assess the ability of eltrombopag to maintain a platelet count sufficient to facilitate initiation of antiviral therapy, to minimise antiviral therapy dose reductions and to avoid permanent discontinuation of antiviral therapy. The clinical benefit of eltrombopag will be measured by the proportion of subjects who are able to achieve a Sustained Virological Response (SVR).

NCT00516321
Conditions
  1. Hepatitis C, Chronic
Interventions
  1. Drug: eltrombopag
  2. Drug: placebo
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

There are two genetic variants (rs12979860 and rs8099917) mapping near IL28B associated with both interferon-induced SVR and spontaneous HCV clearance.

Genotyping of the IL28B polymorphisms (rs12979860 and rs8099917) was conducted.

Genotypes at rs12979860 were coded as: CC=1, CT or TT=0; rs8099917 was coded as TT=1, GT or GG=0.. Number of Par.

Primary Outcomes

Description: Participants with SVR were defined as those with undetectable Hepatitis C Virus (HCV) ribonucleic acid (RNA) at 24 weeks post-completion of the treatment period of the DB Phase.

Measure: Number of Participants With Sustained Virologic Response (SVR) in the Double-blind (DB) Antiviral Treatment Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Secondary Outcomes

Description: Participants were assessed for a shift from a baseline platelet count of <75 Gi/L to a count >=90 Gi/L during the OL Phase (up to 9 weeks). Local laboratories were used for platelet function tests. Platelet counts were measured by blood draw.

Measure: Number of Participants Whose Platelet Count Increased From a Baseline Count of <75 Gi/L to a Count Greater Than or Equal to (>=) 90 Giga (10^9) Cells Per Liter (Gi/L) During the Open-label (OL) Pre-Antiviral Treatment Phase

Time: From Baseline up to Week 9 in the OL Phase

Description: In the OL Phase, participants initially received the lowest dose of eltrombopag (25 mg QD) for 2 weeks. If after this time the platelet count was <90 Gi/L, participants underwent sequential dose escalation to the next highest dose (50 mg QD for up to 2 weeks), with further dose escalations to 75 mg QD (up to 2 weeks) and 100 mg QD (up to a maximum of 3 weeks) if platelet counts remained <90 Gi/L. Participants who achieved platelet count >=90 Gi/L on any of the eltrombopag doses in the OL Phase initiated antiviral therapy in the DB Phase.

Measure: Number of Participants Receiving the Indicated Doses of Eltrombopag in the OL Phase Who Initiated Antiviral Therapy (Peginterferon Alfa-2a and Ribavirin) in the DB Phase

Time: From Baseline up to Week 9 in the OL Phase

Description: Blood taken from peripheral blood vessels was used for the measurement of platelet counts. The Last On Treatment assessment refers to the actual last treatment assessment, not necessarily to the End of Treatment assessment entered by the Investigator.

Measure: Median Platelet Count at the Indicated Time Points During the OL Phase

Time: OL Phase: Baseline; Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, and 9; Antiviral Baseline (up to Week 10); End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 62); 12-week FU (up to Week 70); and 24-week FU (up to Week 82)

Description: Blood taken from peripheral blood vessels was used for the measurement of platelet counts.

Measure: Median Platelet Count at the Indicated Time Points During the DB Phase

Time: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)

Description: The minimum platelet count with antiviral therapy was categorized as follows: <25 Gi/L; >=25 to <50 Gi/L; >=50 to <90 Gi/L; >=90 to <150 Gi/L; >=150 Gi/L to <200 Gi/L; >=200 Gi/L to <400 Gi/L; and >=400 Gi/L.

Measure: Number of Participants in the Indicated Categories for Minimum Platelet Count With Antiviral Therapy During the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: RVR is defined as the absence of detectable HCV RNA after 4 weeks of antiviral treatment. eRVR is defined as the absence of detectable HCV RNA after 4 weeks of antiviral treatment that persisted through Week 12.

Measure: Number of Participants With Rapid Virological Response (RVR) and Extended RVR (eRVR) During the DB Phase

Time: From Baseline up to Week 12

Description: EVR is defined as a clinically significant reduction from Baseline in HCV RNA (>=2 log10 decrease in HCV RNA or undetectable HCV RNA) after 12 weeks of antiviral treatment. cEVR, a subset of EVR, is defined exclusively as undetectable HCV RNA after 12 weeks of antiviral treatment.

Measure: Number of Participants With Early Virological Response (EVR) and Complete EVR (cEVR) During the DB Phase

Time: From Baseline up to Week 12

Description: ETR is defined as the absence of detectable HCV RNA at the end of antiviral treatment. SVR12 is defined as the absence of detectable HCV RNA at the end of antiviral treatment and the 12-week follow-up assessment.

Measure: Number of Participants With End of Treatment Response (ETR) and Sustained Virological Response at Week 12 of Follow-up (SVR12) During the DB Phase

Time: From Baseline up to Week 36 or Week 60 (for participants with Genotype 2/3) or up to Week 60 (for participants with Non-Genotype 2/3)

Description: Participants were assigned a score equal to the number of times their dose of antiviral therapy (peginterferon or ribavirin) was reduced (0=no dose reductions [DRs]; 1=one DR; 2=two DRs; 3=three DRs; >3=more than three DRs). Where possible, every effort was made to maintain the recommended dose of antiviral therapy for the treatment duration in the DB Phase. However, where dose modification of antiviral therapy was required due to safety concerns, it was performed by the Investigator as per the region-specific product labels of peginterferon and ribavirin.

Measure: Number of Participants in the Indicated Categories for Antiviral Therapy Dose Reductions in the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: Time to first dose reduction was calculated as the time period from the first dose to the first dose reduction.

Measure: Time to First Dose Reduction of Peginterferon Alfa-2a and Ribavirin Therapy in the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: The assigned dose in the DB Phase of peginterferon alfa-2a was 180 micrograms (mcg). For peginterferon dose modification, downward adjustments in one level increments was considered. The lowest dose of peginterferon alfa-2a that was allowed to be administered was 45 mcg. Where dose adjustment was required for moderate to severe adverse reactions (clinical and/or laboratory), an initial dose reduction to 135 mcg was generally adequate. In some cases, a dose reduction to 90 mcg or 45mcg was necessary. Dose increases toward the original dose were considered when the adverse reaction was resolved.

Measure: Number of Participants With the Indicated Levels of Peginterferon Dose Reductions in the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: The following participants were considered to have discontinued from antiviral therapy: participants who were lost to follow-up; participants who withdrew for any reason; participants who died; participants who otherwise did not complete their planned course of antiviral therapy for any reason. The planned duration of antiviral therapy was 48 weeks for participants with Non-Genotype 2/3 and 24 or 48 weeks for participants with Genotype 2/3.

Measure: Number of Participants Who Prematurely Discontinued Antiviral Therapy in the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: There are two genetic variants (rs12979860 and rs8099917) mapping near IL28B associated with both interferon-induced SVR and spontaneous HCV clearance. Genotyping of the IL28B polymorphisms (rs12979860 and rs8099917) was conducted. IL28B genotype distribution by response to antiviral therapy (SVR and RVR) for both treatment arms was assessed. The effect of genotype was tested by comparing participants that carried 2 copies of the IL28B favorable response allele versus the others (recessive model). Genotypes at rs12979860 were coded as: CC=1, CT or TT=0; rs8099917 was coded as TT=1, GT or GG=0.

Measure: Number of Participants (Par.) Categorized as Responders (R) and Non-responders (NR) for SVR and RVR to Antiviral Therapy in the Indicated Variants of Interleukin 28B (IL28B) (or Interferon, Lambda 3) During the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: Blood samples for the assessment of clinical chemistry parameters were taken at intervals throughout the study. Participants with the worst-case shift from BL during the DB Phase are reported, per severity grades by DAIDS, for levels of calcium (low=hypocalcemia; high=hypercalcemia), glu. (low=hypoglycemia; high=hyperglycemia), pot. (low=hypokalemia; high=hyperkalemia), and sod. (low=hyponatremia; high=hypernatremia). Per the DAIDS toxicity table, the grade ranges for each parameter are as follows: Grade (G) 1=mild; G2=moderate; G3=severe; G4=potentially life-threatening.

Measure: Number of Par. With the Indicated Shift From Baseline (BL) in Severity Grades for Clinical Chemistry Parameters (Calcium, Glucose [Glu.], Potassium [Pot.], and Sodium [Sod.]), Per Division of Acquired Immunodeficiency Syndrome (DAIDS) During the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: Blood samples for the assessment of hematology parameters were taken at intervals throughout the study. Participants with the worst-case shift from BL during the DB Phase are reported, per severity grades by DAIDS, for levels of hemoglobin (low=anemia), lymphocytes (low=lymphocytopenia), total neutrophils (low=neutropenia), and white blood cells (low=leukocytopenia). Per the DAIDS toxicity table, grade ranges for each parameter are as follows: Grade (G) 1=mild; G2=moderate; G3=severe; G4=potentially life-threatening.

Measure: Number of Participants With the Indicated Shifts From BL in Severity Grades for for Hematology Parameters (Hemoglobin, Lymphocytes [Lym.], Total Neutrophils [Tot Neu.], and White Blood Cells [WBC]), Per DAIDS During the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: Ophthalmic (pertaining to eye) assessments were performed during the study. A cataract event is defined as an event ascertained to be a cataract (opacity or cloudiness of the lens of the eye, causing impairment of vision) by at least one of the CEC members (comprised of expert ophthalmologists who provided objective medical review of the blinded ophthalmic data). Per the CEC, cataract events were categorized as: (1) Cataract Progression (CP; progression of cataracts present at BL); and (2) Incident Cataract (IC; development of new cataracts). One eye=unilateral; both eyes=bilateral.

Measure: Number of Participants in the Indicated Categories for Cataract Event During the DB Phase, Per Clinical Events Committee (CEC) Adjudication During the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: Duplicate 12-lead ECGs were required at Screening/BL, Antiviral BL, and at 12 weekly intervals during the study. The investigator assigned an ECG status of normal, abnormal, CS, or NCS; a status of "abnormal" alone indicates that the investigator did not determine if ECG was CS or NCS. Normal, all ECG parameters within accepted normal ranges. Abnormal, ECG finding(s) outside of normal ranges. CS, ECG with a CS abnormality that meets exclusion criteria. NCS, ECG with an abnormality not CS or meeting exclusion criteria, per Investigator, based on reasonable standards of clinical judgment.

Measure: Number of Participants Assessed as Normal and Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at the Indicated Time Points During the DB Phase

Time: DB Phase: Antiviral BL (up to Week 10); End of Treatment (up to Week 52); and 24-week FU (up to Week 72)

Description: Duplicate 12-lead ECGs were required at Screening/BL, Antiviral BL, and at 12 weekly intervals during the study. The number of participants with a CS or a NCS change from baseline in ECG status was reported, as determined by the Investigator based on a reasonable standard of clinical judgment. "Not applicable" indicates that information was not provided by the investigator on whether the change from baseline ECG was CS or NCS.

Measure: Number of Participants With CS and NCS Change From Baseline for 12-lead ECG at the Indicated Time Points During the DB Phase

Time: End of Treatment (up to Week 52); and 24-week FU (up to Week 72)

Description: Participant's blood pressure was measured at the indicated time points during the study. Systolic blood pressure is a measure of blood pressure while the heart is beating. Diastolic blood pressure is a measure of blood pressure while the heart is relaxed. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Measure: Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points During the DB Phase

Time: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)

Description: Heart rate was measured in participants at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Measure: Mean Change From Baseline in Heart Rate at the Indicated Time Points During the DB Phase

Time: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)

Description: The weight of participants was recorded at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Measure: Mean Change From Baseline in Weight at the Indicated Time Points During the DB Phase

Time: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)

Description: The BMI for participants was calculated at the indicated time points as body weight in kilograms divided by height in meters squared. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Measure: Mean Change From Baseline in Body Mass Index (BMI) at the Indicated Time Points During the DB Phase

Time: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)

2 Randomised, Placebo-controlled, Multi-centre Study to Assess the Efficacy and Safety of Eltrombopag in Thrombocytopenic Subjects With Hepatitis C Virus (HCV) Infection Who Are Otherwise Eligible to Initiate Antiviral Therapy (Peginterferon Alfa-2b Plus Ribavirin)

The purpose of this study is to assess the ability of eltrombopag to maintain a platelet count sufficient to facilitate initiation of antiviral therapy, to minimise antiviral therapy dose reductions and to avoid permanent discontinuation of antiviral therapy. The clinical benefit of eltrombopag will be measured by the proportion of subjects who are able to achieve a Sustained Virological Response (SVR).

NCT00529568
Conditions
  1. Hepatitis C, Chronic
Interventions
  1. Drug: eltrombopag
  2. Drug: placebo
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

There are two genetic variants (rs12979860 and rs8099917) mapping near IL28B associated with both interferon-induced SVR and spontaneous HCV clearance.

Genotypes at rs12979860 were coded as: CC=1, CT or TT=0; rs8099917 was coded as TT=1, GT or GG=0.. Number of Participants With the Indicated Shift From Baseline (BL) in Severity Grades for Clinical Chemistry Parameters (Calcium, Glucose [Glu.],

Primary Outcomes

Description: Participants with SVR are defined as those with non-detectable Hepatitis C Virus (HCV) ribonucleic acid (RNA) at the end of treatment and all subsequent planned visits up to 24 weeks post-completion of the treatment period of the DB Phase.

Measure: Number of Participants With Sustained Virologic Response (SVR) in the Double-blind (DB) Antiviral Treatment Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Secondary Outcomes

Description: Participants were assessed for a shift from a baseline platelet count of <75 Gi/L to a count >=100 Gi/L during the OL Phase (up to 9 weeks). Local laboratories were used for platelet function tests. Platelet counts were measured by blood draw.

Measure: Number of Participants Whose Platelet Count Increased From a Baseline Count of <75 Gi/L to a Count Greater Than or Equal to (>=) 100 Giga (10^9) Cells Per Liter (Gi/L) During the Open-label (OL) Pre-Antiviral Treatment Phase

Time: From Baseline up to Week 9 in the OL Phase

Description: In the OL Phase, participants initially received the lowest dose of eltrombopag (25 mg QD) for 2 weeks. If after this time the platelet count was <100 Gi/L, participants underwent sequential dose escalation to the next highest dose (50 mg QD for up to 2 weeks), with further dose escalations to 75 mg QD (up to 2 weeks) and 100 mg QD (up to a maximum of 3 weeks) if platelet counts remained <100 Gi/L. Participants who achieved platelet counts >=100 Gi/L when receiving any of the eltrombopag doses in the OL Phase initiated antiviral therapy in the DB Phase.

Measure: Number of Participants Receiving the Indicated Doses of Eltrombopag in the OL Phase Who Initiated Antiviral Therapy (Peginterferon Alfa-2a and Ribavirin) in the DB Phase

Time: From Baseline up to Week 9 in the OL Phase

Description: Blood taken from peripheral blood vessels was used for the measurement of platelet counts. The Last On Treatment assessment refers to the actual last treatment assessment, not necessarily to the End of Treatment assessment entered by the Investigator.

Measure: Median Platelet Count at the Indicated Time Points During the OL Phase

Time: OL Phase: Baseline; Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, and 9; Antiviral Baseline (up to Week 10); End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 62); 12-week FU (up to Week 70); and 24-week FU (up to Week 82)

Description: Blood taken from peripheral blood vessels was used for the measurement of platelet counts. The Last On Treatment assessment refers to the actual last treatment assessment, not necessarily to the End of Treatment assessment entered by the Investigator.

Measure: Median Platelet Count at the Indicated Time Points During the DB Phase

Time: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)

Description: The minimum platelet count with antiviral therapy was categorized as follows: <25 Gi/L; >=25 to <50 Gi/L; >=50 to <90 Gi/L; >=90 to <150 Gi/L; >=150 Gi/L to <200 Gi/L; >=200 Gi/L to <400 Gi/L; and >=400 Gi/L.

Measure: Number of Participants in the Indicated Categories for Minimum Platelet Count With Antiviral Therapy

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: RVR is defined as the absence of detectable HCV RNA after 4 weeks of antiviral treatment. eRVR is defined as the absence of detectable HCV RNA after 4 weeks of antiviral treatment that persisted through Week 12.

Measure: Number of Participants With Rapid Virological Response (RVR) and Extended RVR (eRVR) During the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: EVR is defined as a clinically significant reduction from Baseline in HCV RNA (>=2 log10 drop or undetectable) after 12 weeks of antiviral treatment. cEVR is defined as undetectable HCV RNA after 12 weeks of antiviral treatment.

Measure: Number of Participants With Early Virological Response (EVR) and Complete EVR (cEVR) During the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: ETR is defined as the absence of detectable HCV RNA at the end of antiviral treatment. SVR12 is defined as the absence of detectable HCV RNA at the end of antiviral treatment and the 12-week follow-up assessment.

Measure: Number of Participants With End of Treatment Response (ETR) and Sustained Virological Response at Week 12 of Follow-up (SVR12) During the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: Participants were assigned a score equal to the number of times their dose of antiviral therapy (peginterferon or ribavirin) was reduced (0=no dose reductions [DRs]; 1=one DR; 2=two DRs; 3=three DRs; >3=more than three DRs). When possible, every effort was made to maintain the recommended dose of antiviral therapy for the treatment duration in the DB Phase. However, when dose modification of antiviral therapy was required due to safety concerns, it was performed by the Investigator as per the region-specific product labels of peginterferon and ribavirin.

Measure: Number of Participants in the Indicated Categories for Antiviral Therapy Dose Reductions in the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: Time to first dose reduction was calculated as the time period from the first dose to the first dose reduction.

Measure: Time to First Dose Reduction of Peginterferon Alfa-2a and Ribavirin Therapy in the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: The assigned dose in the DB Phase of peginterferon alfa-2a was 180 micrograms (µg). For peginterferon dose modification, downward adjustments in one-level increments were considered. The lowest dose of peginterferon alfa-2a that was allowed to be administered was 45 µg. When dose adjustment was required for moderate to severe adverse reactions (clinical and/or laboratory), an initial dose reduction to 135 µg was generally adequate. In some cases, a dose reduction to 90 µg or 45 µg was necessary. Dose increases toward the original dose were considered when the adverse reaction was resolved.

Measure: Number of Participants With the Indicated Levels of Peginterferon Dose Reductions in the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: The following participants were considered to have discontinued antiviral therapy: participants who were lost to follow-up; participants who withdrew for any reason; participants who died; participants who otherwise did not complete their planned course of antiviral therapy for any reason. The planned duration of antiviral therapy was 48 weeks for participants with Non-Genotype 2/3 and 24 or 48 weeks for participants with Genotype 2/3.

Measure: Number of Participants Who Prematurely Discontinued Antiviral Therapy in the DB Phase

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: There are two genetic variants (rs12979860 and rs8099917) mapping near IL28B associated with both interferon-induced SVR and spontaneous HCV clearance. IL28B genotype distribution by response to antiviral therapy (SVR/RVR responders: those who achieved SVR/RVR; SVR/RVR non-responders: those who did not achieve SVR/RVR) was assessed. The effect of genotype was tested by comparing participants that carried 2 copies of the IL28B favorable response allele versus the others (recessive model). Genotypes at rs12979860 were coded as: CC=1, CT or TT=0; rs8099917 was coded as TT=1, GT or GG=0.

Measure: Number of Participants Categorized as Responders (R) and Non-responders (NR) for SVR and RVR to Antiviral Therapy in the Indicated Variants of Interleukin 28B (IL28B) (or Interferon, Lambda 3)

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: Blood samples for the assessment of clinical chemistry parameters were taken at intervals throughout the study. Participants with the worst-case shift from BL during the DB Phase are reported, per severity grades by DAIDS, for levels of calcium (low=hypocalcemia; high=hypercalcemia), glu. (low=hypoglycemia; high=hyperglycemia), pot. (low=hypokalemia; high=hyperkalemia), and sod. (low=hyponatremia; high=hypernatremia). Per the DAIDS toxicity table, the grade ranges for each parameter are as follows: Grade (G) 1=mild; G2=moderate; G3=severe; G4=potentially life-threatening.

Measure: Number of Participants With the Indicated Shift From Baseline (BL) in Severity Grades for Clinical Chemistry Parameters (Calcium, Glucose [Glu.], Potassium [Pot.], and Sodium [Sod.]), Per Division of Acquired Immunodeficiency Syndrome (DAIDS)

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: Blood samples for the assessment of hematology parameters were taken at intervals throughout the study. Participants with the worst-case shift from BL during the DB Phase are reported, per severity grades by DAIDS, for levels of hemoglobin (low=anemia), lymphocytes (low=lymphocytopenia), total neutrophils (low=neutropenia), and white blood cells (low=leukocytopenia). Per the DAIDS toxicity table, grade ranges for each parameter are as follows: Grade (G) 1=mild; G2=moderate; G3=severe; G4=potentially life-threatening.

Measure: Number of Participants With the Indicated Shifts From BL in Severity Grades for for Hematology Parameters (Hemoglobin, Lymphocytes [Lym.], Total Neutrophils [Tot Neu.], and White Blood Cells [WBC]), Per DAIDS

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: Ophthalmic (pertaining to eye) assessments were performed during the study. A cataract event is defined as an event ascertained to be a cataract (opacity or cloudiness of the lens of the eye, causing impairment of vision) by at least one of the CEC members (comprised of expert ophthalmologists who provided objective medical review of the blinded ophthalmic data). Per the CEC, cataract events were categorized as: (1) Cataract Progression (CP; progression of cataracts present at BL); and (2) Incident Cataract (IC; development of new cataracts). One eye=unilateral; both eyes=bilateral.

Measure: Number of Participants in the Indicated Categories for Cataract Event During the DB Phase, Per Clinical Events Committee (CEC) Adjudication

Time: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)

Description: Duplicate 12-lead ECGs were required at Screening/BL, Antiviral BL, and at 12 weekly intervals during the study. The number of participants with an ECG status of normal, abnormal, CS, or NCS, as determined by the Investigator, was reported. Normal, all ECG parameters within accepted normal ranges. Abnormal, ECG finding(s) outside of normal ranges. CS, ECG with a CS abnormality that meets exclusion criteria. NCS, ECG with an abnormality not CS or meeting exclusion criteria, per Investigator, based on reasonable standards of clinical judgment.

Measure: Number of Participants Assessed as Normal and Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at the Indicated Time Points During the DB Phase

Time: DB Phase: Antiviral BL (up to Week 10); End of Treatment (up to Week 52); and 24-week FU (up to Week 72)

Description: Duplicate 12-lead ECGs were required at Screening/BL, Antiviral BL, and at 12 weekly intervals during the study. The number of participants with a CS and a NCS change from baseline in ECG status, as determined by the Investigator, was reported. CS, ECG with a CS abnormality that meets exclusion criteria. NCS, ECG with an abnormality not CS or meeting exclusion criteria, per Investigator, based on reasonable standards of clinical judgment. "Not applicable" indicates that information was not provided by the investigator on whether the change from baseline ECG was CS or NCS.

Measure: Number of Participants With CS and NCS Change From Baseline for 12-lead ECG at the Indicated Time Points During the DB Phase

Time: End of Treatment (up to Week 52); and 24-week FU (up to Week 72)

Description: Participant's blood pressure was measured at the indicated time points during the study. Systolic blood pressure is a measure of blood pressure while the heart is beating. Diastolic blood pressure is a measure of blood pressure while the heart is relaxed. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Measure: Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points During the DB Phase

Time: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)

Description: Heart rate was measured in participants at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Measure: Mean Change From Baseline in Heart Rate at the Indicated Time Points During the DB Phase

Time: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)

Description: The weight of participants was recorded at the indicated time points. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Measure: Mean Change From Baseline in Weight at the Indicated Time Points During the DB Phase

Time: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)

Description: The BMI for participants was calculated at the indicated time points as body weight in kilograms divided by height in meters squared. Mean change from Baseline was calculated as the value at the indicated time points minus the value at Baseline.

Measure: Mean Change From Baseline in Body Mass Index (BMI) at the Indicated Time Points During the DB Phase

Time: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)

3 Epidemiological Study to Evaluate the Management of Patients With Chronic Hepatitis C and Previous Treatment Failure

The purpose of this study is to describe the management of patients with chronic hepatitis C and previous treatment failure.

NCT01033045
Conditions
  1. Hepatitis C
MeSH:Hepatitis A Hepatitis C Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

To determine the presence of the polymorphism rs12979860 in the gene IL 28B located on chromosome 19..

The rs12979860 polymorphism in the gene IL 28B that is located on chromosome 19 showed to be strongly associated with the development of sustained viral response (SVR) in patients with chronic hepatitis C treated with PEG-IFN-α/RBV.

Primary Outcomes

Measure: Describe the management of patients with chronic hepatitis C and previous treatment failure

Time: 6 years

Secondary Outcomes

Measure: To know the frequency of the causes for not responding to the previous treatment: lack of adherence to treatment, incomplete dose of antiviral treatment, insufficient treatment duration or treatment resistance.

Time: 6 years

Measure: To assess the percentage of patients with previous treatment failure who are not candidates for re-treatment and its causes.

Time: 6 years

Measure: To evaluate the implementation of current recommendations based on the cause of the previous therapeutic failure, in patients with chronic hepatitis C in whom a new course of the antiviral treatment is decided to be administered.

Time: 6 years

Measure: To know the causes of the dose modifications and withdrawal of treatment during the follow-up period in patients who start re-treatment.

Time: 6 years

Measure: To know the percentage of patients that achieve sustained viral response when implementing the recommendations based on the cause of the previous therapeutic failure.

Time: 6 years

Description: The rs12979860 polymorphism in the gene IL 28B that is located on chromosome 19 showed to be strongly associated with the development of sustained viral response (SVR) in patients with chronic hepatitis C treated with PEG-IFN-α/RBV. Patients with this polymorphism clear the virus more easily.

Measure: To determine the presence of the polymorphism rs12979860 in the gene IL 28B located on chromosome 19.

Time: 6

Measure: Compare the management of patients with chronic hepatitis C prior treatment failure before and after the appearance of new treatments.

Time: 3

4 An Open-Label Pilot Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of ABT-450 With Ritonavir (ABT-450/r) Dosed in Combination With ABT-072 and Ribavirin (RBV) in Treatment-Naive Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of ABT-450 with ritonavir (ABT-450/r) dosed in combination with ABT-072 and ribavirin (RBV) in treatment-naïve participants with genotype 1 chronic hepatitis C virus (HCV) infection.

NCT01221298
Conditions
  1. Hepatitis C
  2. HCV
  3. Chronic Hepatitis C Infection
  4. Hepatitis C Genotype 1
Interventions
  1. Drug: ABT-450
  2. Drug: ABT-072
  3. Drug: Ribavirin
  4. Drug: Ritonavir
MeSH:Infection Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic
HPO:Chronic active hepatitis Chronic hepatitis Hepatitis

Time to confirmed hepatitis C virus (HCV) ribonucleic acid (RNA) ≥ lower limit of quantitation (LLOQ) (2 consecutive measurements ≥ LLOQ) at any point in the post-treatment period among participants with HCV RNA < LLOQ at the end of treatment.. Inclusion Criteria: - Chronic hepatitis C, genotype 1 infection with interleukin 28B (IL28B) rs12979860 genotype C/C. - Liver biopsy within 3 years with histology consistent with hepatitis C virus (HCV) - induced liver damage, with no evidence of cirrhosis or liver pathology due to any cause other than chronic HCV. - Treatment naïve male or female between the ages of 18 and 65. - Females must be postmenopausal for at least 2 years or surgically sterile.

Inclusion Criteria: - Chronic hepatitis C, genotype 1 infection with interleukin 28B (IL28B) rs12979860 genotype C/C. - Liver biopsy within 3 years with histology consistent with hepatitis C virus (HCV) - induced liver damage, with no evidence of cirrhosis or liver pathology due to any cause other than chronic HCV. - Treatment naïve male or female between the ages of 18 and 65. - Females must be postmenopausal for at least 2 years or surgically sterile.

Primary Outcomes

Description: Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (< 25 IU/mL).

Measure: Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Quantitation (LLOQ) From Week 4 Through Week 12

Time: Week 4 through Week 12

Secondary Outcomes

Description: Analysis of participants with HCV RNA levels below 1000 IU/mL at Week 2.

Measure: Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) < 1000 International Units Per Milliliter (IU/mL)

Time: Week 2

Description: Analysis of percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (< 25 IU/mL).

Measure: Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Below the Lower Limit of Quantitation (LLOQ) at Week 4

Time: Week 4

Description: Sustained Virologic Response 12 (SVR12) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (< LLOQ; < 25 IU/mL) 12 weeks after the last dose of study drug.

Measure: Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment

Time: Post-treatment Day 1 to Post-treatment Week 12

Description: Sustained Virologic Response 24 (SVR24) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; < 25 IU/mL) 24 weeks after the last dose of study drug.

Measure: Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment

Time: Post-treatment Day 1 to Post-treatment Week 24

Description: The time to failure to suppress was defined as first day a participant met any virologic stopping criteria during treatment. The virologic stopping criteria also includes failure to achieve a 2 log10 IU/mL decrease in HCV RNA by Week 1, failure to achieve HCV RNA lower limit of detection (LLOD) for participants who previously achieved HCV RNA < LLOD.

Measure: Time to Failure to Suppress or Rebound During Treatment

Time: Day 1 through Week 12

Description: Time to confirmed hepatitis C virus (HCV) ribonucleic acid (RNA) ≥ lower limit of quantitation (LLOQ) (2 consecutive measurements ≥ LLOQ) at any point in the post-treatment period among participants with HCV RNA < LLOQ at the end of treatment.

Measure: Time to Virologic Relapse Through 24 Weeks Post-treatment

Time: Post-treatment Day 1 to Post-treatment Week 24

5 Open-Label, Single Arm Evaluation of BMS-790052 (Daclatasvir) in Combination With Peg-Interferon Alfa-2a and Ribavirin in Black-African Americans, Latinos and White-Caucasians With Chronic Hepatitis C Genotype 1 Infection

The purpose of this study is to compare the rates of sustained virologic response in each cohort (Black-African Americans, Latinos) in this study to historical rate.

NCT01389323
Conditions
  1. Hepatitis C
Interventions
  1. Drug: Daclatasvir
  2. Drug: Peg-Interferon Alfa-2a
  3. Drug: Ribavirin
MeSH:Hepatitis A Hepatitis C Hepatitis
HPO:Hepatitis

Some participants were represented in more than one race/ethnicity cohort.. Percentage of Participants Achieving Sustained Virologic Response at Post-treatment Week 12 (SVR12) With rs12979860 Single Nucleotide Polymorphisms at Baseline in the Interleukin-28B Gene.

Primary Outcomes

Description: SVR12 was defined as Hepatitis C Virus (HCV) RNA levels Measure: Percentage of Participants Achieving Sustained Virologic Response at Post-treatment Week 12 (SVR12)

Time: Post-treatment Week 12

Secondary Outcomes

Description: SVR12 was defined as Hepatitis C Virus (HCV) RNA levels Measure: Percentage of Participants Achieving Sustained Virologic Response at Post-treatment Week 12 (SVR12) With rs12979860 Single Nucleotide Polymorphisms at Baseline in the Interleukin-28B Gene

Time: Post-treatment Week 12

Description: The limit of detection for HCV RNA levels was 10 IU/mL and the LLOQ was 25 IU/mL. Data for post-treatment Weeks 36 and 48 were based on participants who had achieved virologic response (defined as HCV RNA levels Measure: Percentage of Participants With Hepatitis C Virus (HCV) RNA Levels Time: Weeks 1, 2, 4, 6, 8, 12; both Weeks 4 and 12; end-of-treatment (up to 48 weeks), or post-treatment Week 24


Description: The limit of detection for HCV RNA levels was 10 IU/mL and the LLOQ was 25 IU/mL. For analysis purpose, participants were assigned to following 3 race/ethnicity cohorts: Black/African American, Latino, and White non-Latino. Some participants were represented in more than one race/ethnicity cohort.

Measure: Percentage of Participants With Hepatitis C Virus (HCV) RNA Levels Time: Weeks 1, 2, 4, 6, 8, 12; both Weeks 4 and 12; end-of-treatment (up to 48 weeks), or post-treatment Weeks 12 and 24

Description: An AE was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Treatment-related AE was defined as an AE that had certain, probable, possible, or unknown relationship to study drug. For analysis purpose, participants were assigned to following 4 race/ethnicity cohorts: Black/African American, White/Caucasian, Latino and Non-Latino. Some participants were represented in more than one race/ethnicity cohort.

Measure: Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Treatment-related AEs, and Who Died

Time: From first dose to last dose plus 7 days (treatment period [TP]) through 48 weeks after the end of TP (follow-up period [FUP])

6 Study of Parameters of Early Hepatitis C Virus Dynamics for Predicting the Outcome of Standard Interferon Therapy With Chinese Cohort

The purpose of this study is to determine whether the outcome of interferon therapy on HCV infected patients can be early precisely predicted with a novel mathematic method with Chinese population.

NCT01434212
Conditions
  1. Hepatitis
Interventions
  1. Drug: Interferon Alfa-2b, Ribavirin
MeSH:Hepatitis A Hepatitis C Hepatitis
HPO:Hepatitis

IL28 gene polymorphism,rs8099917,rs12979860,etc.

Primary Outcomes

Description: Blood HCV RNA copies were assayed with Roche - COBAS® AmpliPrep/COBAS® TaqMan® HCV Test.

Measure: Blood HCV RNA Copies

Time: 0h,8h,10h,12h,18h,24h,37h,43h,3d,7d,2w,4w,6w,12w,24w,48w

Secondary Outcomes

Description: IL28 gene polymorphism,rs8099917,rs12979860,etc

Measure: IL-28B polymorphism

Time: Baseline

Description: During the first 3 days, blood samples are collected for PBMC separation and microarray analysis.

Measure: Microarray Analysis of PBMC Gene Expression

Time: Baseline,8h,18h,3d

Description: HCV NS5A is cloned into T vector and sequenced for evolutionary analysis.

Measure: HCV genotype

Time: Baseline

Description: Co-infection status are analyzed.

Measure: Blood Anti-HCV,HBV Antibody

Time: Baseline

Description: Deep sequencing is used for blood serum HCV genome analysis.

Measure: HCV genome sequencing

Time: 0h,8h,10h,12h,18h,24h,37h,43h,3d

Description: ALT AST are assayed to detect the hepatic function.

Measure: Alanine Aminotransferase (ALT) and Aspartate transaminase (AST)

Time: Baseline,4w,6w,12w,24w,48w

Description: Fibrosis is analyzed with Fibroscan.

Measure: Fibrosis stage

Time: Baseline,4w,12w,24w,48w

Description: The distribution and absolute count of the different types of blood cells are assayed.

Measure: Regular blood test

Time: Baseline,4w,12w,24w,48w

Description: Electrocardiography is taken to avoid severe side effects.

Measure: Electrocardiography

Time: Baseline,4w,12w,24w,48w

Description: Patients are asked whether they take alcohol or smoke cigarettes during the therapy period.

Measure: Alcohol ,smoking condition

Time: Baseline,4w,12w,24w,48w

Description: Patients will be asked about their drug usage history.

Measure: Drug abuse history

Time: Baseline

7 A Phase 3 Evaluation of BMS-790052 in Combination With Peg-Interferon Alfa-2a and Ribavirin in Treatment Naive Subjects With Chronic Hepatitis C Genotype 4

The purpose of this study is to compare the sustained virologic response at post treatment Week 12 for each cohort (BMS-790052/Pegylated-interferon alfa 2a (pegIFNα-2a)/Ribavirin (RBV) versus placebo/PegIFNα-2a/RBV).

NCT01448044
Conditions
  1. Hepatitis C
Interventions
  1. Drug: BMS-790052 (NS5A Replication Complex Inhibitor)
  2. Drug: Placebo matching BMS-790052
  3. Drug: Pegylated-interferon alfa 2a
  4. Drug: Ribavirin
MeSH:Hepatitis A Hepatitis C Hepatitis
HPO:Hepatitis

Participants in the placebo arm did not have visits beyond post treatment Week 24.. Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) or Sustained Virologic Response at Follow-up Week 24 (SVR24) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene.

Primary Outcomes

Description: Participants were assessed for sustained virologic response 12 weeks post treatment (SVR12) defined as hepatitis C virus (HCV) RNA levels < lower limit of quantitation (LLOQ was 25 IU/mL), target detected (TD) or target not detected (TND) at post-treatment Week 12.

Measure: Percentage of Participants With 12 Week Sustained Virologic Response (SVR12)

Time: Week 12 (Follow-up period)

Secondary Outcomes

Description: Participants who achieved HCV RNA levels below LLOQ ie, 25 international unit per milliliter (IU/mL). Participants in the placebo arm did not have visits beyond post treatment Week 24.

Measure: Percentage of Participants Who Achieve HCV Ribonucleic Acid (RNA) < Limit of Quantification (LLOQ)

Time: Treatment Weeks 1, 2, 4, 6, 8 and 12; Weeks 4 and 12; End of treatment (EOT); Post treatment Week 24; Post treatment Week 48

Description: Participants who achieved HCV RNA undetectable ie, 10 international units per milliliter (IU/mL). Participants in the placebo arm did not have visits beyond post treatment Week 24.

Measure: Percentage of Participants With Undetectable Hepatitis C Virus (HCV) RNA Levels

Time: Treatment Weeks 1, 2, 4, 6, 8 and 12; Weeks 4 and 12, End of treatment (EOT), Post treatment Week 24, Post treatment Week 48

Description: Participants categorized into three genotypes based on SNPs in the IL28B gene were assessed for SVR12 and SVR24, defined as response in which hepatitis C virus RNA levels below lower limit of quantitation or below target detected or target not detected at follow-up Week 12 and Week 24 respectively.

Measure: Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) or Sustained Virologic Response at Follow-up Week 24 (SVR24) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene

Time: Post Treatment Weeks 12, 24

Description: AE was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalisation.

Measure: Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died

Time: From Day 1 (start of study treatment) up to Follow-up Week 4

8 A Phase 3, Open Label Study of Safety and Efficacy With BMS-790052 Plus Peg-Interferon Alfa 2a and Ribavirin in Previously Untreated HCV Patients Coinfected With Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV)

The purpose of this open label study is to evaluate the safety and efficacy of daclatasvir plus pegylated interferon-alfa 2a and ribavirin in untreated hepatitis C virus in patients coinfected with HIV

NCT01471574
Conditions
  1. Hepatitis C, Genotype 1
Interventions
  1. Drug: Daclatasvir
  2. Drug: Ribavirin
  3. Drug: PEG-Interferon alfa 2a
MeSH:Hepatitis A Hepatitis C Hepatitis
HPO:Hepatitis

Participants who received HAART, maintained HIV RNA <40 copies/mL, and experienced confirmed HIV RNA ≥ 400 copies/mL were determined.. Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene.

Primary Outcomes

Description: SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy.

Measure: Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)

Time: Follow-up Week 12

Secondary Outcomes

Description: Participants who achieved HCV RNA levels lower than the LLOQ i.e., 25 IU/ml, TD or TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy.

Measure: Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND)

Time: Week 1, 2, 4, 6, 8, 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24

Description: Participants who achieved HCV RNA levels lower than the LLOQ, TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy.

Measure: Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND)

Time: Week 1, 2, 4, 6, 8, and 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24

Description: Participants who received HAART, maintained HIV RNA <40 copies/mL, and experienced confirmed HIV RNA ≥ 400 copies/mL were determined.

Measure: Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL

Time: End of treatment (up to Week 48)

Description: Percentages calculated as number of responders/number who received treatment.

Measure: Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene

Time: Follow-up Week 12

Description: Adverse event was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threating, an important medical event, or a congenital anomaly/birth defect; or required prolonged hospitalization. HAART=highly active antiretroviral therapy.

Measure: Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation

Time: From Day 1 to 7 days post last dose of study treatment (up to Week 48)

9 A Phase 3 Japanese Study of BMS-790052 Plus BMS-650032 Combination Therapy in Chronic Hepatitis C Genotype 1b Infected Subjects Who Are Non Response to Interferon Plus Ribavirin and Interferon Based Therapy Ineligible Naive/Intolerant

The purpose of this study is to assess the anti-viral activity of BMS-790052 and BMS-650032 combination therapy in Japanese subjects.

NCT01497834
Conditions
  1. Hepatitis C
Interventions
  1. Drug: BMS-790052 (Daclatasvir)
  2. Drug: BMS-650032 (Asunaprevir)
MeSH:Hepatitis A Hepatitis C Hepatitis
HPO:Hepatitis

Proportion of subjects with SVR24 by IL28B status [CC, CT, or TT genotype at the IL28B rs12979860 single nucleotide polymorphisms (SNP)].

Primary Outcomes

Description: SVR24 - sustained virologic response at follow-up Week 24 (after end of treatment)

Measure: Antiviral activity, as determined by the proportion of subjects with SVR24

Time: After 24 weeks of the last dose

Secondary Outcomes

Measure: Antiviral activity, as determined by the proportion of subjects who achieve Hepatitis C virus (HCV) ribonucleic acid (RNA) below lower limit of quantitation (LLOQ) target detected or not detected

Time: Weeks 1, 2, 4, 6, 8, 10 and 12; Weeks 4 and 12; End of treatment (EOT), or post treatment Week 12

Measure: Antiviral activity, as determined by the proportion of subjects who achieve HCV RNA below LLOQ, target not detected

Time: Weeks 1, 2, 4, 6, 8, 10 and 12; Weeks 4 and 12; EOT, or post treatment Week 12, post treatment Week 24

Measure: Safety, as measured by the frequency of serious adverse events (SAEs), discontinuations due to adverse events (AEs), AEs by intensity and laboratory abnormalities by toxicity grade

Time: End of treatment plus 7 days

Measure: Proportion of subjects with SVR24 by IL28B status [CC, CT, or TT genotype at the IL28B rs12979860 single nucleotide polymorphisms (SNP)]

Time: Follow-up Week 24

10 A Phase 3, Open-Label Study With Asunaprevir and Daclatasvir Plus Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) (P/R) (QUAD) for Subjects Who Are Null or Partial Responders to Peginterferon Alfa 2a or 2b Plus Ribavirin With Chronic Hepatitis C Genotypes 1 or 4 Infection

The purpose of this study is to assess efficacy, as determined by the proportion of subjects with Sustained Virologic Response at Post-Treatment Week 12 (SVR12), defined as Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Limit of quantitation (LOQ) at post-treatment Week 12.

NCT01573351
Conditions
  1. Hepatitis C Virus
Interventions
  1. Drug: Asunaprevir
  2. Drug: Daclatasvir
  3. Drug: Peg-interferon Alfa-2a
  4. Drug: Ribavirin
MeSH:Hepatitis C Hepatitis
HPO:Hepatitis

Proportion of subjects with SVR12 (HCV RNA < LOQ at post-treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28 gene.

Primary Outcomes

Measure: Proportion of genotype 1 subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for all subjects infected with HCV genotype 1

Time: At 12 weeks post-treatment

Secondary Outcomes

Measure: On-treatment safety, as measured by frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) through the end of treatment

Time: Through the end of treatment (maximum up to 24 weeks) plus 7 days

Measure: Proportion of subjects with SVR12 (HCV RNA < LOQ at post-treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28 gene

Time: At post-treatment Week 12

Measure: Proportion of subjects with HCV RNA undetectable

Time: Weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [Extended rapid virologic response (eRVR)], end of treatment (up to 24 weeks), post-treatment Week 12 or post-treatment Week 24

Measure: Proportion of subjects with HCV RNA < LOQ

Time: Weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12, end of treatment (up to 24 weeks), post-treatment Week 24 (SVR24)

Measure: Proportion of patients with SVR12 (HCV RNA < LOQ at post-treatment Week 12) for HCV genotype 4 subjects

Time: Post-treatment Week 12

11 A Phase 3 Study With Asunaprevir and Daclatasvir (DUAL) for Null or Partial Responders to Peginterferon Alfa and Ribavirin (P/R), Intolerant or Ineligible to P/R Subjects and Treatment-Naive Subjects With Chronic Hepatitis C Genotype 1b Infection

The purpose of this study is to estimate efficacy, as determined by the proportion of subjects with Sustained virologic response at post-treatment Week 12 (SVR12), defined as Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Limit of quantitation (LOQ) at post-treatment Week 12, for subjects who are prior null or partial responders to P/R or who are treatment-naive.

NCT01581203
Conditions
  1. Hepatitis C Virus
Interventions
  1. Drug: Asunaprevir (ASV)
  2. Drug: Daclatasvir (DCV)
  3. Drug: Pegylated-interferon alfa 2a (PegIFN)
  4. Drug: Ribavirin (RBV)
MeSH:Hepatitis C Hepatitis
HPO:Hepatitis

Proportion of genotype 1b subjects with SVR12 (HCV RNA < LOQ at post treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28B gene for each cohort.

Primary Outcomes

Measure: Proportion of treated subjects with SVR12, defined as HCV RNA < LOQ at post treatment Week 12, for subjects who are prior null or partial responders to P/R or are treatment-naive

Time: At 12 weeks post-treatment

Secondary Outcomes

Measure: Proportion of treated subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for subjects who are intolerant or ineligible to P/R

Time: Post-treatment Week 12

Measure: On treatment safety, as measured by frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs)

Time: End of Treatment (up to 48 weeks) plus 7 days

Measure: Differences in rates of selected grade 3-4 laboratory abnormalities during the first 12 weeks between treatments (ASV + DCV vs PBO) for naive subjects

Time: Up to first 12 weeks

Measure: Proportion of genotype 1b subjects with SVR12 (HCV RNA < LOQ at post treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28B gene for each cohort

Time: Post-treatment Week 12

Description: eRVR = Extended rapid virologic response, EOT = End of treatment

Measure: Proportion of genotype 1b subjects with HCV RNA undetectable

Time: At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [eRVR]; EOT (up to 24 weeks), post-treatment Week 12, or post-treatment Week 24 for each cohort

Measure: Proportion of genotypes 1b subjects with HCV RNA < LOQ

Time: At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [VR(4&12)]; EOT (up to 24 weeks), post-treatment Week 24 (SVR24) for each cohort

Measure: Proportion of subjects with anemia

Time: At 12 weeks post-treatment

Measure: Proportion of subjects with rash

Time: At 12 weeks post-treatment

12 A Phase 2, Open-Label Study of Daclatasvir (BMS-790052) and TMC435 in Combination With or Without Ribavirin (RBV) For Treatment-Naive Subjects or Null Responders to Prior Peginterferon Alfa (PegIFN)/RBV Therapy With Genotype 1 Chronic Hepatitis C

The purpose of this study is to assess the safety and efficacy of daclatasvir and simeprevir with and without ribavirin for genotype 1 chronic hepatitis C virus infection in patients who are treatment-naive or null responders to previous pegylated interferon/ribavirin therapy.

NCT01628692
Conditions
  1. Hepatitis C Virus
Interventions
  1. Drug: Daclatasvir
  2. Drug: Simeprevir
  3. Drug: Ribavirin
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.. Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) by rs12979860 Single Nucleotide Polymorphisms in the IL-28B Gene Categories.

Primary Outcomes

Description: SVR12 rate was defined as hepatitis C virus (HCV) RNA levels to be Measure: Percentage of Participants With Sustained Virologic Response Rate at Post-treatment Week 12 (SVR12)

Time: Post Treatment Week 12 (Follow-up period)

Secondary Outcomes

Description: RVR was defined as hepatitis C virus (HCV) RNA levels to be Measure: Percentage of Participants With Rapid Virologic Response (RVR) at Week 4

Time: Week 4

Description: cEVR was defined as hepatitis C virus (HCV) RNA levels to be Measure: Percentage of Participants With Complete Early Virologic Response (cEVR)

Time: Week 12

Description: eRVR were defined as hepatitis C virus (HCV) RNA levels to be Measure: Percentage of Participants With Extended Rapid Virologic Response (eRVR)

Time: Week 4 and Week 12

Description: EOTR were defined as hepatitis C virus (HCV) RNA levels Measure: Percentage of Participants With End of Treatment Response (EOTR)

Time: End of treatment (Week 24)

Description: Participants were categorized into 3 genotypes based on single nucleotide polymorphisms in the IL28B gene. SVR12 was defined as hepatitis C virus (HCV) RNA levels below lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

Measure: Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) by rs12979860 Single Nucleotide Polymorphisms in the IL-28B Gene Categories

Time: Baseline, post-treatment Week 12 (Follow-up period)

Description: AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.

Measure: Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died

Time: From start of treatment (Day 1) up to 7 days post last dose of study treatment (Week 24)

13 A Phase II Multicenter, Parallel-Group, Randomized, Dose-Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Following 12 Weeks of Oral Administration of GSK2336805 With Pegylated Interferon and Ribavirin in Treatment-Naïve Subjects With Chronic Genotype 1 or 4 Hepatitis C Infection

GSK2336805 is a novel hepatitis C virus (HCV) non-structural 5A (NS5A) inhibitor being developed for the treatment of chronic HCV infection. This Phase II, multicenter, parallel-group, randomized, dose-ranging study will assess the safety and tolerability, antiviral activity, and pharmacokinetics of GSK2336805 at 2 dose levels (40 and 60 mg) in combination with pegylated interferon alfa-2a (PEG) and ribavirin (RIBA) in approximately 100 treatment-naïve subjects with chronic genotype 1 HCV infection. In a separate nonrandomized single-arm cohort, up to 15 treatment-naïve subjects with genotype 4 chronic HCV infection will be enrolled in parallel at the dose level of 60 mg of GSK2336805.

NCT01648140
Conditions
  1. Hepatitis C, Chronic
Interventions
  1. Drug: GSK2336805 40 mg
  2. Drug: GSK2336805 60 mg
  3. Drug: Pegylated interferon alpha-2a
  4. Drug: Ribavirin
  5. Drug: Telaprevir
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

Randomization will be stratified by interleukin 28B (IL28B) rs12979860 status (C/C versus carriage of the T allele), HCV genotype (1a vs. 1b), and plasma HCV Ribonucleic Acid (RNA) (<800,000 IU/mL versus ≥800,000 IU/mL).

Primary Outcomes

Description: eRVR is defined as plasma HCV ribonucleic acid (RNA) Measure: Number of Participants Achieving eRVR

Time: Week 4 and Week 12

Description: An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign(including an abnormal laboratory finding), symptom, or disease(new or exacerbated) temporally associated with the use of a medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, a congenital anomaly/birth defect, important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.

Measure: Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) up to Week 12

Time: From the start of study treatment up to Week 12

Description: Blood pressure measurements were taken to observe vital signs and included SBP and DBP at the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and Post-treatment (PT) Follow Up (FU) Weeks 4, 12 and 24. Change from Baseline in SBP and DBP is summarized for each post-Baseline assessment up to Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) up to 12-week treatment period

Description: Vital sign monitoring included heart rate, measured at the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4, 12 and 24. Change from Baseline in heart rate is summarized for each post-Baseline assessment upto Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Heart Rate at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) and Day 2, Weeks 1, 2, 4, 6, 8, and 12

Description: Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell count at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the basophils, eosinophils, lymphocytes, total neutrophils, platelet count and white blood cell count values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12

Description: Blood samples were collected for the measurement of red blood cell count at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the red blood cell count values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Red Blood Cell Count at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12

Description: Blood samples were collected for the measurement of hemoglobin at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the hemoglobin values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Hemoglobin at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12

Description: Blood samples were collected for the measurement of hematocrit at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the hematocrit values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Hematocrit at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12

Description: Blood samples were collected for the measurement of mean corpuscle volume at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the mean corpuscle volume values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12

Description: Blood samples were collected for the measurement of albumin at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the albumin values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Albumin at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12

Description: Blood samples were collected for the measurement of ALP, ALT, AST, CK and GGT at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4 Change from Baseline in the ALP, ALT, AST, CK and GGT values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Creatine Kinase (CK) and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12

Description: Blood samples were collected for the measurement of direct bilirubin, total bilirubin and creatinine at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the direct bilirubin, total bilirubin and creatinine values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Direct Bilirubin, Total Bilirubin and Creatinine at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12

Description: Blood samples were collected for the measurement of Chloride, bicarbonate, glucose, potassium, sodium, inorganic phosphorus and urea/BUN at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the chloride, bicarbonate, glucose, potassium, sodium, inorganic phosphorus and urea/BUN values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Chloride, Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12

Description: Blood samples were collected for the measurement of Creatinine Clearance at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. It is estimated by Cockcroft-Gault Equation. Change from Baseline in the Creatinine Clearance values are summarized for each post-Baseline assessment until Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Creatinine Clearance at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8 and 12

Description: Urine samples were collected for urinalysis at Baseline, Weeks 2, 12, 18, 24, 48 and PT FU Weeks 4. Number of participants with shift from Baseline in urinalysis to normal (NL), abnormal (ANL) and missing (MIS) data up to Week 12 are summarized. Urine bilirubin (UBIL), urine glucose (UGLU), urine ketones (UKET), urine leukocyte esterase test (ULET) for detecting WBC, urine nitrite (UNIT), urine occult blood (UOB) were performed with dipstick method. Urine microscopy (UM) is performed to detect bacteria (BAC), red blood cells (RBC) and white blood cells (WBC). Other urinalysis parameter included urine pH (UpH) and urine specific gravity (USG). Baseline value is defined as the last Pre-treatment value observed.

Measure: Number of Participants With Shift From Baseline in Urinalysis Data up to Week 12

Time: Baseline (Week 0), Weeks 2 and 12

Description: The ECG parameter heart rate was measured at Baseline, Weeks 1 and 12. Change from Baseline in ECG heart rate is summarized for each post-Baseline assessment up to Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Electrocardiographic (ECG) Heart Rate Values at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) and Weeks 1 and 12

Description: The ECG parameters including PR interval, QRS duration, uncorrected QT interval, QTcB, QTcF were measured at Baseline, Weeks 1 and 12. Change from Baseline in ECG parameters are summarized for each post-Baseline assessment up to Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval and QT Interval Corrected Bazett's Formula (QTcB), QT Interval Corrected Using Fridericia's Formula (QTcF) Values at the Indicated Time Points up to Week 12

Time: Baseline (Week 0) and Weeks 1 and 12

Secondary Outcomes

Description: An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign(including an abnormal laboratory finding), symptom, or disease(new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, a congenital anomaly/birth defect, important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition.

Measure: Number of Participants With Any AEs and Any SAEs After Week 12

Time: From Week 12 up to PT Week 24 FU

Description: Blood samples for the determination of HCV RNA levels were collected at Screening and Baseline, every study visit during the Treatment Period, and at PT FU Weeks 4, 12, and 24. vRVR is defined as plasma HCV RNA Measure: Number of Participants Achieving Very Rapid Virologic Response (vRVR), Rapid Virologic Response (RVR), Complete Early Virologic Response (cEVR), Sustained Virologic Response 12 and 24 (SVR12 and SVR24) With Response Guided Treatment (RGT)

Time: From the start of the treatment up to PT FU Week 24

Description: Plasma pharmacokinetic (PK) samples were collected for all participants on Day 1 (0 hour [h]-1h, 1h-4h, 4h-8h, 8h-20h), Day 2 (Predose [20-28h]), Week 4 (Predose [20-28h], 0h-1h, 1h-4h, 4h-8h, 8h-20h, 20h-28h) and Week 12 (Predose [20-28h]). PK Population is comprised of all participants who received GSK2336805 and underwent plasma PK sampling (intensive or sparse) during the study.

Measure: Mean GSK2336805 Plasma Concentrations on Day 1, Day 2, Week 4, and Week 12

Time: Day 1, Day 2, Week 4, and Week 12

Description: Blood samples for PK analysis of GSK2336805 was obtained on Week 4+1 day at predose and at 1, 2, 4, 7, 24 hours post-dose.

Measure: Maximum Plasma Concentration (Cmax) and Concentration at the End of the Dosing Interval (Ctau) of GSK2336805 at Week 4

Time: Week 4 (24 h post dose)

Description: Blood samples for PK analysis of GSK2336805 was obtained on Week 4+1 day at predose and at 1, 2, 4, 7, 24 hours postdose.

Measure: Time of Maximal Plasma Concentration (Tmax) of GSK2336805 at Week 4

Time: Week 4 (24 h post dose)

Description: Blood samples for PK analysis of GSK2336805 was obtained on Week 4+1 day at predose and at 1, 2, 4, 7 and 24 hours postdose.

Measure: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) at Week 4

Time: Week 4 (24 h post dose)

Description: Blood samples for PK analysis of GSK2336805 was obtained on Week 4+1 day at predose and at 1, 2, 4, 7 and 24 hours postdose. CL/F was calculated as dose divided by AUC(0-tau).

Measure: Apparent Clearance (CL/F) at Week 4

Time: Week 4 (24 h post dose)

Description: Blood samples for PK analysis of GSK2336805 was obtained on Week 4+1 day at predose and at 1, 2, 4, 7 and 24 hours postdose. Vz/F was calculated as dose divided by (AUC[0-tau] lambda z) where lambda z is the terminal phase rate constant.

Measure: Apparent Volume of Distribution (Vz/F) at Week 4

Time: Week 4 (24 h post dose)

Description: Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell count at the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT Week 4. Change from Baseline in the basophils, eosinophils, lymphocytes, total neutrophils platelet count and white blood cell count values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell Count at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: Blood samples were collected for the measurement of red blood cell count at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the red blood cell count values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Red Blood Cell Count at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: Blood samples were collected for the measurement of hemoglobin at the the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the hemoglobin values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Hemoglobin at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: Blood samples were collected for the measurement of hematocrit at the the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the hematocrit values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Hematocrit at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: Blood samples were collected for the measurement of mean corpuscle volume at the the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the mean corpuscle volume values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Mean Corpuscle Volume at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: Blood samples were collected for the measurement of albumin at the the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the albumin values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Albumin at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: Blood samples were collected for the measurement of ALP, ALT, AST, CK and GGT at the the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the ALP, ALT, AST, CK and GGT values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in ALP, ALT, AST, CK and GGT at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: Blood samples were collected for the measurement of total bilirubin and creatinine at the the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Week 4. Change from Baseline in the direct bilirubin, total bilirubin and creatinine values are summarized for each post-Baseline assessment afterl Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Total Bilirubin and Creatinine at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: Blood pressure measurements were taken to observe vital signs and included SBP and DBP at the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. As defined in the Reporting Analysis Plan (RAP) for this protocol, the supplemental final data package generated for this study after Week 12 only provided graphical displays of vital signs (e.g., change from baseline for heart rate and blood pressure) to facilitate clinical interpretation and data summarization. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. All abnormal values and statistical summary tables were not available after week 12.

Measure: Mean Change From Baseline in SBP and DBP at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: Vital sign monitoring included heart rate, measured at the Baseline, Day 2, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. As defined in the Reporting Analysis Plan (RAP) for this protocol, the supplemental final data package generated for this study after Week 12 only provided graphical displays of vital signs (e.g., change from Baseline for heart rate and blood pressure) to facilitate clinical interpretation and data summarization. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed. All abnormal values and statistical summary tables were not available after week 12.

Measure: Mean Change From Baseline in Heart Rate at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: The ECG data was only collected "Perform as needed", therefore, no such summary table was generated. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in ECG Heart Rate Values at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: The ECG data was only collected "Perform as needed", therefore, no such summary table was generated. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QTcB, QTcF Values at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: Blood samples were collected for the measurement of Chloride, bicarbonate, glucose, potassium, sodium, inorganic phosphorus and urea/bun at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the Chloride, Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus and Urea/Bun values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last pre-treatment value observed.

Measure: Mean Change From Baseline in Chloride, Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus and Urea/BUN at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: Blood samples were collected for the measurement of estimated creatinine clearance by Cockcroft-Gault formula at the Baseline, Weeks 1, 2, 4, 6, 8, 12, 18, 24, 30, 36, 42, 48 and PT FU Weeks 4. Change from Baseline in the estimated creatinine clearance values are summarized for each post-Baseline assessment after Week 12. Change from Baseline was calculated as the individual post-Baseline value minus the Baseline value. Baseline value is defined as the last Pre-treatment value observed.

Measure: Mean Change From Baseline in Creatinine Clearance at the Indicated Time Points After Week 12

Time: Baseline (Week 0) and Weeks 18, 24, 30, 36, 42, 48 and PT FU Week 4

Description: Correlation of individual GSK2336805 40 mg and 60 mg with Week 4 plasma AUC(0-tau) versus eRVR Status (eRVR and no eRVE) was performed. eRVR is defined as plasma HCV RNA Measure: Correlation of Individual GSK2336805 Dose With Week 4 Plasma AUC(0-tau) Versus eRVR Status

Time: Week 4 and Week 12

Description: Correlation of Individual GSK2336805 40 mg and 60 mg dose with Week 4 maximum plasma concentration (Cmax), pre-dose concentration (C0), concentration at the end of the dosing interval (Ctau) versus eRVR status (eRVR and no eRVR) was performed. eRVR is defined as plasma HCV RNA Measure: Correlation of Individual GSK2336805 Dose With Week 4 Plasma Cmax, Ctau, C0 Versus eRVR Status

Time: Week 4 and Week 12

Description: Correlation of individual GSK2336805 40 mg and 60 mg with Week 4 plasma AUC(0-tau) versus eRVR Status (RVR and no eVE) was performed. RVR is defined as plasma HCV RNA Measure: Correlation of Individual GSK2336805 Dose With Week 4 Plasma AUC(0-tau) Versus RVR Status

Time: Week 4

Description: Correlation of Individual GSK2336805 40 mg and 60 mg dose with Week 4 maximum plasma concentration (Cmax), pre-dose concentration (C0), concentration at the end of the dosing interval (Ctau) versus RVR status (RVR and no RVR) was performed. RVR is defined as plasma HCV RNA Measure: Correlation of Individual GSK2336805 Dose With Week 4 Plasma Cmax, Ctau, C0 Versus RVR Status

Time: Week 4

Description: Correlation of individual GSK2336805 dose with pre-dose plasma concentration at Week 4 and Week 12 versus eRVR status was performed. eRVR is defined as plasma HCV RNA Measure: Correlation of Individual GSK2336805 Dose With Pre-dose Plasma Concentration at Week 4 and Week 12 Versus eRVR Status

Time: Week 4 and Week 12

Description: Correlation GSK2336805 pre-dose plasma concentration (ng/mL) on Day 2 versus reduction in HCV RNA (log IU/mL) on Day 2 was performed. As defined in the RAP for this protocol, correlations between GSK2336805 dose, and selected PK parameters and virological outcomes was analyzed only with graphical presentations to facilitate clinical interpretation and data summarization. These data were also provided in by-participant data listings. Therefore, no statistical summary tables are available.

Measure: Correlation GSK2336805 Pre-dose Plasma Concentration on Day 2 Versus Reduction in HCV RNA on Day 2

Time: Day 2

14 An International, Multi-Center Study Evaluating the Correlation of IL28B Genotypes With Patient Demographics and Disease Characteristics in Patients With Chronic Hepatitis C

This multicenter study will evaluate the correlation of interleukin 28B (IL28B) genotypes with disease characteristics and demographics in treatment-naïve and treatment-experienced chronic hepatitis C patients, including patients with HIV co-infection. There will be a single study visit for testing.

NCT01675427
Conditions
  1. Hepatitis C, Chronic
Interventions
  1. Other: Interleukin 28B testing
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

Number of Participants With Interleukin 28B (IL28B) Genotype rs12979860 by Cirrhosis Status and Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Genotype: Treatment-Naive.

Cirrhosis status was based upon previous biopsy or noninvasive assessment captured prior to treatment, if applicable.. Number of Participants With IL28B Genotype rs12979860 by Cirrhosis Status and HCV RNA Genotype: Treatment-Experienced.

Cirrhosis status was based upon previous biopsy or noninvasive assessment captured prior to treatment, if applicable.. Number of Participants With IL28B Genotype rs12979860 by Liver Fibrosis Stage and HCV RNA Genotype: Treatment-Naive.

Liver fibrosis stage was based upon previous biopsy using these five categories and captured prior to treatment, if applicable.. Number of Participants With IL28B Genotype rs12979860 by Liver Fibrosis Stage and HCV RNA Genotype: Treatment-Experienced.

Liver fibrosis stage was based upon previous biopsy using these five categories and captured prior to treatment, if applicable.. Number of Participants With IL28B Genotype rs12979860 by METAVIR Liver Fibrosis Stage and HCV RNA Genotype: Treatment-Naive.

Liver fibrosis stage was based upon previous biopsy using the METAVIR scoring system and captured prior to treatment, if applicable.. Number of Participants With IL28B Genotype rs12979860 by METAVIR Liver Fibrosis Stage and HCV RNA Genotype: Treatment-Experienced.

Liver fibrosis stage was based upon previous biopsy using the METAVIR scoring system and captured prior to treatment, if applicable.. Mean FibroScan Values by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Naive.

Mean FibroScan values were determined by averaging the values of all participants within each arm and expressed in kilopascals (kPa).. Mean FibroScan Values by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Experienced.

Mean FibroScan values were determined by averaging the values of all participants within each arm and expressed in kPa.. Number of Participants With IL28B Genotype rs12979860 by METAVIR Liver Inflammation Grade and HCV RNA Genotype: Treatment-Naive.

Liver inflammation grade was based upon previous biopsy using the METAVIR scoring system and captured prior to treatment, if applicable.. Number of Participants With IL28B Genotype rs12979860 by METAVIR Liver Inflammation Grade and HCV RNA Genotype: Treatment-Experienced.

Liver inflammation grade was based upon previous biopsy using the METAVIR scoring system and captured prior to treatment, if applicable.. Number of Participants With IL28B Genotype rs12979860 by Gender: Treatment-Naive.

Demographic characteristics, including gender, were obtained from medical records and/or participant interview at the Study Visit.. Number of Participants With IL28B Genotype rs12979860 by Gender: Treatment-Experienced.

Demographic characteristics, including gender, were obtained from medical records and/or participant interview at the Study Visit.. Number of Participants With IL28B Genotype rs12979860 by Ethnic Origin: Treatment-Naive.

Demographic characteristics, including self-reported ethnic origin, were obtained from medical records and/or participant interview at the Study Visit.. Number of Participants With IL28B Genotype rs12979860 by Ethnic Origin: Treatment-Experienced.

Demographic characteristics, including self-reported ethnic origin, were obtained from medical records and/or participant interview at the Study Visit.. Mean Body Weight by IL28B Genotype rs12979860: Treatment-Naive.

Mean body weight was calculated by averaging the values of all participants within each arm and expressed in kilograms (kg).. Mean Body Weight by IL28B Genotype rs12979860: Treatment-Experienced.

Mean body weight was calculated by averaging the values of all participants within each arm and expressed in kg.. Mean Body Mass Index (BMI) by IL28B Genotype rs12979860: Treatment-Naive.

Each participant's BMI was calculated as weight divided by height-squared, expressed in kilograms per meter-squared (kg/m^2), and mean BMI was calculated by averaging the values of all participants within each arm.. BMI by IL28B Genotype rs12979860: Treatment-Experienced.

Each participant's BMI was calculated as weight divided by height-squared, expressed in kg/m^2, and mean BMI was calculated by averaging the values of all participants within each arm.. Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype: Treatment-Naive.

HCV RNA genotype was obtained from medical records.. Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype: Treatment-Experienced.

HCV RNA genotype was obtained from medical records.. Mean HCV RNA Level by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Naive.

Mean HCV RNA level was calculated by averaging the values of all participants within each arm and expressed in log10 international units per milliliter (log10 IU/mL).. Mean HCV RNA Level by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Experienced.

Mean HCV RNA level was calculated by averaging the values of all participants within each arm and expressed in log10 IU/mL.. Mean Alanine Aminotransferase (ALT) Ratio by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Naive.

Mean ALT ratio was calculated by averaging the values of all participants within each arm.. Mean ALT Ratio by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Experienced.

Mean ALT ratio was calculated by averaging the values of all participants within each arm.. Mean Aspartate Aminotransferase (AST) Ratio by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Naive.

Mean AST ratio was calculated by averaging the values of all participants within each arm.. Mean AST Ratio by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Experienced.

Mean AST ratio was calculated by averaging the values of all participants within each arm.. Mean Platelet Count by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Naive.

Mean platelet count was calculated by averaging the values of all participants within each arm and expressed in 10^9 cells per liter (10^9 cells/L).. Mean Platelet Count by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Experienced.

Mean platelet count was calculated by averaging the values of all participants within each arm and expressed in 10^9 cells/L.. Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype and Region: Treatment-Naive.

HCV RNA genotype was obtained from medical records, and geographic region of study site was documented during intake/enrollment.. Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype and Region: Treatment-Experienced.

HCV RNA genotype was obtained from medical records, and geographic region of study site was documented during intake/enrollment.. Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype and Country: Treatment-Naive (Table 1 of 2 [G1, G2, G3]).

HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.. Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype and Country: Treatment-Naive (Table 2 of 2 [G4, Other, Total]).

HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.. Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype and Country: Treatment-Experienced (Table 1 of 2 [G1, G2, G3]).

HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.. Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype and Country: Treatment-Experienced (Table 2 of 2 [G4, Other, Total]).

HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.. Number of Participants With IL28B Genotype rs12979860 by IL28B Genotype rs8099917 Category: Treatment-Naive.

Participants underwent blood sampling at the Study Visit to determine IL28B genotype.. Number of Participants With IL28B Genotype rs12979860 by IL28B Genotype rs8099917 Category: Treatment-Experienced.

HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.. Number of Participants With IL28B Genotype rs12979860 by Type of Virological Response in the First 12 Weeks of Treatment and HCV RNA Genotype.

Number of Participants With IL28B Genotype rs12979860 by Type of Virological Response at End of Treatment and HCV RNA Genotype.

Undetectable viral loads include those below the LLOD for the assay performed, which may vary from site to site.. Number of Participants With IL28B Genotype rs12979860 by Overall Virological Response Type and HCV RNA Genotype.

Primary Outcomes

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype (Genotype 1 [G1], Genotype 2 [G2], Genotype 3 [G3], Genotype 4 [G4], and all other genotypes [Other]) and cirrhosis status ('Cirrhosis/transition to cirrhosis' or 'No cirrhosis') were obtained from medical records. Cirrhosis status was based upon previous biopsy or noninvasive assessment captured prior to treatment, if applicable.

Measure: Number of Participants With Interleukin 28B (IL28B) Genotype rs12979860 by Cirrhosis Status and Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Genotype: Treatment-Naive

Time: Study Visit 1 (single study visit)

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and cirrhosis status were obtained from medical records. Cirrhosis status was based upon previous biopsy or noninvasive assessment captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs12979860 by Cirrhosis Status and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and cirrhosis status were obtained from medical records. Cirrhosis status was based upon previous biopsy or noninvasive assessment captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs8099917 by Cirrhosis Status and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and cirrhosis status were obtained from medical records. Cirrhosis status was based upon previous biopsy or noninvasive assessment captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs8099917 by Cirrhosis Status and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver fibrosis stage ('Cirrhotic,' 'Transition to cirrhosis,' 'Advanced fibrosis noncirrhotic,' 'Mild/minimal fibrosis,' and 'No fibrosis') were obtained from medical records. Liver fibrosis stage was based upon previous biopsy using these five categories and captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs12979860 by Liver Fibrosis Stage and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver fibrosis stage ('Cirrhotic,' 'Transition to cirrhosis,' 'Advanced fibrosis noncirrhotic,' 'Mild/minimal fibrosis,' and 'No fibrosis') were obtained from medical records. Liver fibrosis stage was based upon previous biopsy using these five categories and captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs12979860 by Liver Fibrosis Stage and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver fibrosis stage ('Cirrhotic,' 'Transition to cirrhosis,' 'Advanced fibrosis noncirrhotic,' 'Mild/minimal fibrosis,' and 'No fibrosis') were obtained from medical records. Liver fibrosis stage was based upon previous biopsy using these five categories and captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs8099917 by Liver Fibrosis Stage and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver fibrosis stage ('Cirrhotic,' 'Transition to cirrhosis,' 'Advanced fibrosis noncirrhotic,' 'Mild/minimal fibrosis,' and 'No fibrosis') were obtained from medical records. Liver fibrosis stage was based upon previous biopsy using these five categories and captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs8099917 by Liver Fibrosis Stage and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver fibrosis stage (Stage F0, Stage F1, Stage F2, Stage F3, or Stage F4) were obtained from medical records. Liver fibrosis stage was based upon previous biopsy using the METAVIR scoring system and captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs12979860 by METAVIR Liver Fibrosis Stage and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver fibrosis stage (Stage F0, Stage F1, Stage F2, Stage F3, or Stage F4) were obtained from medical records. Liver fibrosis stage was based upon previous biopsy using the METAVIR scoring system and captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs12979860 by METAVIR Liver Fibrosis Stage and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver fibrosis stage (Stage F0, Stage F1, Stage F2, Stage F3, or Stage F4) were obtained from medical records. Liver fibrosis stage was based upon previous biopsy using the METAVIR scoring system and captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs8099917 by METAVIR Liver Fibrosis Stage and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver fibrosis stage (Stage F0, Stage F1, Stage F2, Stage F3, or Stage F4) were obtained from medical records. Liver fibrosis stage was based upon previous biopsy using the METAVIR scoring system and captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs8099917 by METAVIR Liver Fibrosis Stage and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver elastography (FibroScan) were obtained from medical records. FibroScan values were based upon previous noninvasive assessment captured prior to treatment, if applicable. Mean FibroScan values were determined by averaging the values of all participants within each arm and expressed in kilopascals (kPa).

Measure: Mean FibroScan Values by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver elastography (FibroScan) were obtained from medical records. FibroScan values were based upon previous noninvasive assessment captured prior to treatment, if applicable. Mean FibroScan values were determined by averaging the values of all participants within each arm and expressed in kPa.

Measure: Mean FibroScan Values by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver elastography (FibroScan) were obtained from medical records. FibroScan values were based upon previous noninvasive assessment captured prior to treatment, if applicable. Mean FibroScan values were determined by averaging the values of all participants within each arm and expressed in kPa.

Measure: Mean FibroScan Values by IL28B Genotype rs8099917 and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver elastography (FibroScan) were obtained from medical records. FibroScan values were based upon previous noninvasive assessment captured prior to treatment, if applicable. Mean FibroScan values were determined by averaging the values of all participants within each arm and expressed in kPa.

Measure: Mean FibroScan Values by IL28B Genotype rs8099917 and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Secondary Outcomes

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver inflammation grade (Grade A0, Grade A1, Grade A2, or Grade A3) were obtained from medical records. Liver inflammation grade was based upon previous biopsy using the METAVIR scoring system and captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs12979860 by METAVIR Liver Inflammation Grade and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver inflammation grade (Grade A0, Grade A1, Grade A2, or Grade A3) were obtained from medical records. Liver inflammation grade was based upon previous biopsy using the METAVIR scoring system and captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs12979860 by METAVIR Liver Inflammation Grade and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver inflammation grade (Grade A0, Grade A1, Grade A2, or Grade A3) were obtained from medical records. Liver inflammation grade was based upon previous biopsy using the METAVIR scoring system and captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs8099917 by METAVIR Liver Inflammation Grade and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and liver inflammation grade (Grade A0, Grade A1, Grade A2, or Grade A3) were obtained from medical records. Liver inflammation grade was based upon previous biopsy using the METAVIR scoring system and captured prior to treatment, if applicable.

Measure: Number of Participants With IL28B Genotype rs8099917 by METAVIR Liver Inflammation Grade and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including gender, were obtained from medical records and/or participant interview at the Study Visit.

Measure: Number of Participants With IL28B Genotype rs12979860 by Gender: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including gender, were obtained from medical records and/or participant interview at the Study Visit.

Measure: Number of Participants With IL28B Genotype rs12979860 by Gender: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including gender, were obtained from medical records and/or participant interview at the Study Visit.

Measure: Number of Participants With IL28B Genotype rs8099917 by Gender: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including gender, were obtained from medical records and/or participant interview at the Study Visit.

Measure: Number of Participants With IL28B Genotype rs8099917 by Gender: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including self-reported ethnic origin, were obtained from medical records and/or participant interview at the Study Visit.

Measure: Number of Participants With IL28B Genotype rs12979860 by Ethnic Origin: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including self-reported ethnic origin, were obtained from medical records and/or participant interview at the Study Visit.

Measure: Number of Participants With IL28B Genotype rs12979860 by Ethnic Origin: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including self-reported ethnic origin, were obtained from medical records and/or participant interview at the Study Visit.

Measure: Number of Participants With IL28B Genotype rs8099917 by Ethnic Origin: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including self-reported ethnic origin, were obtained from medical records and/or participant interview at the Study Visit.

Measure: Number of Participants With IL28B Genotype rs8099917 by Ethnic Origin: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including pre-treatment body weight, were obtained from medical records and/or participant interview at the Study Visit. Mean body weight was calculated by averaging the values of all participants within each arm and expressed in kilograms (kg).

Measure: Mean Body Weight by IL28B Genotype rs12979860: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including pre-treatment body weight, were obtained from medical records and/or participant interview at the Study Visit. Mean body weight was calculated by averaging the values of all participants within each arm and expressed in kg.

Measure: Mean Body Weight by IL28B Genotype rs12979860: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including pre-treatment body weight, were obtained from medical records and/or participant interview at the Study Visit. Mean body weight was calculated by averaging the values of all participants within each arm and expressed in kg.

Measure: Mean Body Weight by IL28B Genotype rs8099917: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including pre-treatment body weight, were obtained from medical records and/or participant interview at the Study Visit. Mean body weight was calculated by averaging the values of all participants within each arm and expressed in kg.

Measure: Mean Body Weight by IL28B Genotype rs8099917: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including height and pre-treatment body weight, were obtained from medical records and/or participant interview at the Study Visit. Each participant's BMI was calculated as weight divided by height-squared, expressed in kilograms per meter-squared (kg/m^2), and mean BMI was calculated by averaging the values of all participants within each arm.

Measure: Mean Body Mass Index (BMI) by IL28B Genotype rs12979860: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including height and pre-treatment body weight, were obtained from medical records and/or participant interview at the Study Visit. Each participant's BMI was calculated as weight divided by height-squared, expressed in kg/m^2, and mean BMI was calculated by averaging the values of all participants within each arm.

Measure: BMI by IL28B Genotype rs12979860: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including height and pre-treatment body weight, were obtained from medical records and/or participant interview at the Study Visit. Each participant's BMI was calculated as weight divided by height-squared, expressed in kg/m^2, and mean BMI was calculated by averaging the values of all participants within each arm.

Measure: BMI by IL28B Genotype rs8099917: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Demographic characteristics, including height and pre-treatment body weight, were obtained from medical records and/or participant interview at the Study Visit. Each participant's BMI was calculated as weight divided by height-squared, expressed in kg/m^2, and mean BMI was calculated by averaging the values of all participants within each arm.

Measure: BMI by IL28B Genotype rs8099917: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records.

Measure: Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records.

Measure: Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records.

Measure: Number of Participants With IL28B Genotype rs8099917 by HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records.

Measure: Number of Participants With IL28B Genotype rs8099917 by HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA level was obtained from medical records. Mean HCV RNA level was calculated by averaging the values of all participants within each arm and expressed in log10 international units per milliliter (log10 IU/mL).

Measure: Mean HCV RNA Level by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA level was obtained from medical records. Mean HCV RNA level was calculated by averaging the values of all participants within each arm and expressed in log10 IU/mL.

Measure: Mean HCV RNA Level by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA level was obtained from medical records. Mean HCV RNA level was calculated by averaging the values of all participants within each arm and expressed in log10 IU/mL.

Measure: Mean HCV RNA Level by IL28B Genotype rs8099917 and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA level was obtained from medical records. Mean HCV RNA level was calculated by averaging the values of all participants within each arm and expressed in log10 IU/mL.

Measure: Mean HCV RNA Level by IL28B Genotype rs8099917 and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. ALT level was obtained from medical records captured prior to treatment, if applicable. Each participant's ALT ratio was calculated as ALT level divided by the upper limit of normal (55 international units per liter [IU/L] for males and 30 IU/L for females). Mean ALT ratio was calculated by averaging the values of all participants within each arm.

Measure: Mean Alanine Aminotransferase (ALT) Ratio by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. ALT level was obtained from medical records captured prior to treatment, if applicable. Each participant's ALT ratio was calculated as ALT level divided by the upper limit of normal (55 IU/L for males and 30 IU/L for females). Mean ALT ratio was calculated by averaging the values of all participants within each arm.

Measure: Mean ALT Ratio by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. ALT level was obtained from medical records captured prior to treatment, if applicable. Each participant's ALT ratio was calculated as ALT level divided by the upper limit of normal (55 IU/L for males and 30 IU/L for females). Mean ALT ratio was calculated by averaging the values of all participants within each arm.

Measure: Mean ALT Ratio by IL28B Genotype rs8099917 and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. ALT level was obtained from medical records captured prior to treatment, if applicable. Each participant's ALT ratio was calculated as ALT level divided by the upper limit of normal (55 IU/L for males and 30 IU/L for females). Mean ALT ratio was calculated by averaging the values of all participants within each arm.

Measure: Mean ALT Ratio by IL28B Genotype rs8099917 and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. AST level was obtained from medical records captured prior to treatment, if applicable. Each participant's AST ratio was calculated as AST level divided by the upper limit of normal (40 IU/L for males and 25 IU/L for females). Mean AST ratio was calculated by averaging the values of all participants within each arm.

Measure: Mean Aspartate Aminotransferase (AST) Ratio by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. AST level was obtained from medical records captured prior to treatment, if applicable. Each participant's AST ratio was calculated as AST level divided by the upper limit of normal (40 IU/L for males and 25 IU/L for females). Mean AST ratio was calculated by averaging the values of all participants within each arm.

Measure: Mean AST Ratio by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. AST level was obtained from medical records captured prior to treatment, if applicable. Each participant's AST ratio was calculated as AST level divided by the upper limit of normal (40 IU/L for males and 25 IU/L for females). Mean AST ratio was calculated by averaging the values of all participants within each arm.

Measure: Mean AST Ratio by IL28B Genotype rs8099917 and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. AST level was obtained from medical records captured prior to treatment, if applicable. Each participant's AST ratio was calculated as AST level divided by the upper limit of normal (40 IU/L for males and 25 IU/L for females). Mean AST ratio was calculated by averaging the values of all participants within each arm.

Measure: Mean AST Ratio by IL28B Genotype rs8099917 and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Platelet count was obtained from medical records captured prior to treatment, if applicable. Mean platelet count was calculated by averaging the values of all participants within each arm and expressed in 10^9 cells per liter (10^9 cells/L).

Measure: Mean Platelet Count by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Platelet count was obtained from medical records captured prior to treatment, if applicable. Mean platelet count was calculated by averaging the values of all participants within each arm and expressed in 10^9 cells/L.

Measure: Mean Platelet Count by IL28B Genotype rs12979860 and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Platelet count was obtained from medical records captured prior to treatment, if applicable. Mean platelet count was calculated by averaging the values of all participants within each arm and expressed in 10^9 cells/L.

Measure: Mean Platelet Count by IL28B Genotype rs8099917 and HCV RNA Genotype: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. Platelet count was obtained from medical records captured prior to treatment, if applicable. Mean platelet count was calculated by averaging the values of all participants within each arm and expressed in 10^9 cells/L.

Measure: Mean Platelet Count by IL28B Genotype rs8099917 and HCV RNA Genotype: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records, and geographic region of study site was documented during intake/enrollment.

Measure: Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype and Region: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records, and geographic region of study site was documented during intake/enrollment.

Measure: Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype and Region: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records, and geographic region of study site was documented during intake/enrollment.

Measure: Number of Participants With IL28B Genotype rs8099917 by HCV RNA Genotype and Region: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records, and geographic region of study site was documented during intake/enrollment.

Measure: Number of Participants With IL28B Genotype rs8099917 by HCV RNA Genotype and Region: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype and Country: Treatment-Naive (Table 1 of 2 [G1, G2, G3])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype and Country: Treatment-Naive (Table 2 of 2 [G4, Other, Total])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype and Country: Treatment-Experienced (Table 1 of 2 [G1, G2, G3])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With IL28B Genotype rs12979860 by HCV RNA Genotype and Country: Treatment-Experienced (Table 2 of 2 [G4, Other, Total])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With IL28B Genotype rs8099917 by HCV RNA Genotype and Country: Treatment-Naive (Table 1 of 2 [G1, G2, G3])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With IL28B Genotype rs8099917 by HCV RNA Genotype and Country: Treatment-Naive (Table 2 of 2 [G4, Other, Total])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With IL28B Genotype rs8099917 by HCV RNA Genotype and Country: Treatment-Experienced (Table 1 of 2 [G1, G2, G3])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With IL28B Genotype rs8099917 by HCV RNA Genotype and Country: Treatment-Experienced (Table 2 of 2 [G4, Other, Total])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype.

Measure: Number of Participants With IL28B Genotype rs12979860 by IL28B Genotype rs8099917 Category: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype.

Measure: Number of Participants With IL28B Genotype rs12979860 by IL28B Genotype rs8099917 Category: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype.

Measure: Number of Participants With Inosine Triphosphatase (ITPA) Genotype rs7270101 by ITPA Genotype rs1127354 Category: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype.

Measure: Number of Participants With ITPA Genotype rs7270101 by ITPA Genotype rs1127354 Category: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records, and geographic region of study site was documented during intake/enrollment.

Measure: Number of Participants With ITPA Genotype rs1127354 by HCV RNA Genotype and Region: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records, and geographic region of study site was documented during intake/enrollment.

Measure: Number of Participants With ITPA Genotype rs1127354 by HCV RNA Genotype and Region: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records, and geographic region of study site was documented during intake/enrollment.

Measure: Number of Participants With ITPA Genotype rs7270101 by HCV RNA Genotype and Region: Treatment-Naive

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records, and geographic region of study site was documented during intake/enrollment.

Measure: Number of Participants With ITPA Genotype rs7270101 by HCV RNA Genotype and Region: Treatment-Experienced

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With ITPA Genotype rs1127354 by HCV RNA Genotype and Country: Treatment-Naive (Table 1 of 2 [G1, G2, G3])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With ITPA Genotype rs1127354 by HCV RNA Genotype and Country: Treatment-Naive (Table 2 of 2 [G4, Other, Total])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With ITPA Genotype rs1127354 by HCV RNA Genotype and Country: Treatment-Experienced (Table 1 of 2 [G1, G2, G3])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With ITPA Genotype rs1127354 by HCV RNA Genotype and Country: Treatment-Experienced (Table 2 of 2 [G4, Other, Total])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With ITPA Genotype rs7270101 by HCV RNA Genotype and Country: Treatment-Naive (Table 1 of 2 [G1, G2, G3])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With ITPA Genotype rs7270101 by HCV RNA Genotype and Country: Treatment-Naive (Table 2 of 2 [G4, Other, Total])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With ITPA Genotype rs7270101 by HCV RNA Genotype and Country: Treatment-Experienced (Table 1 of 2 [G1, G2, G3])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records, and country of study site was documented during intake/enrollment.

Measure: Number of Participants With ITPA Genotype rs7270101 by HCV RNA Genotype and Country: Treatment-Experienced (Table 2 of 2 [G4, Other, Total])

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and virological response to prior treatment were obtained from medical records. Virological response types within the first 12 weeks of treatment included rapid virological response (RVR), complete early virological response (cEVR), and partial early virological response (pEVR). RVR was defined as an undetectable HCV RNA level within the first 4 weeks, cEVR as an undetectable level within the first 12 weeks, and pEVR as a 2-log drop from Baseline to 12 weeks. Undetectable viral loads include those below the lower limit of detection (LLOD) for the assay performed, which may vary from site to site. Response categories were mutually exclusive, meaning participants could only achieve cEVR/pEVR in the absence of RVR. Participants achieving neither RVR nor cEVR/pEVR were recorded as 'none of the above.'

Measure: Number of Participants With IL28B Genotype rs12979860 by Type of Virological Response in the First 12 Weeks of Treatment and HCV RNA Genotype

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and virological response to prior treatment were obtained from medical records. Virological response types within the first 12 weeks of treatment included RVR, cEVR, and pEVR. RVR was defined as an undetectable HCV RNA level within the first 4 weeks, cEVR as an undetectable level within the first 12 weeks, and pEVR as a 2-log drop from Baseline to 12 weeks. Undetectable viral loads include those below the LLOD for the assay performed, which may vary from site to site. Response categories were mutually exclusive, meaning participants could only achieve cEVR/pEVR in the absence of RVR. Participants achieving neither RVR nor cEVR/pEVR were recorded as 'none of the above.'

Measure: Number of Participants With IL28B Genotype rs8099917 by Type of Virological Response in the First 12 Weeks of Treatment and HCV RNA Genotype

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and virological response to prior treatment were obtained from medical records. Virological response types at the end of treatment included undetectable and detectable HCV RNA level. Undetectable viral loads include those below the LLOD for the assay performed, which may vary from site to site.

Measure: Number of Participants With IL28B Genotype rs12979860 by Type of Virological Response at End of Treatment and HCV RNA Genotype

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and virological response to prior treatment were obtained from medical records. Virological response types at the end of treatment included undetectable and detectable HCV RNA level. Undetectable viral loads include those below the LLOD for the assay performed, which may vary from site to site.

Measure: Number of Participants With IL28B Genotype rs8099917 by Type of Virological Response at End of Treatment and HCV RNA Genotype

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and virological response to prior treatment were obtained from medical records. Overall virological response types included sustained virological response (SVR), relapse, and breakthrough. SVR was defined as undetectable HCV RNA level at 24 weeks post-treatment, relapse as an undetectable level at end of treatment with a detectable level at the last post-treatment measurement, and breakthrough as an undetectable level at 1 or more treatment measurements with a detectable level at end of treatment. Undetectable viral loads include those below the LLOD for the assay performed, which may vary from site to site. Response categories were mutually exclusive. Participants with detectable HCV RNA level at 12 or more treatment measurements and who did not meet SVR criteria were considered nonresponders, and those with insufficient treatment response data were recorded as 'none of the above.'

Measure: Number of Participants With IL28B Genotype rs12979860 by Overall Virological Response Type and HCV RNA Genotype

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine IL28B genotype. HCV RNA genotype and virological response to prior treatment were obtained from medical records. Overall virological response types included SVR, relapse, and breakthrough. SVR was defined as undetectable HCV RNA level at 24 weeks post-treatment, relapse as an undetectable level at end of treatment with a detectable level at the last post-treatment measurement, and breakthrough as an undetectable level at 1 or more treatment measurements with a detectable level at end of treatment. Undetectable viral loads include those below the LLOD for the assay performed, which may vary from site to site. Response categories were mutually exclusive. Participants with detectable HCV RNA level at 12 or more treatment measurements and who did not meet SVR criteria were considered nonresponders, and those with insufficient treatment response data were recorded as 'none of the above.'

Measure: Number of Participants With IL28B Genotype rs8099917 by Overall Virological Response Type and HCV RNA Genotype

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype and hematology data were obtained from medical records. Participants with a history of a hemoglobin level less than 10 grams per deciliter (g/dL) or a drop of more than 3 g/dL at any time during prior treatment for CHC were recorded as 'yes' for this finding.

Measure: Number of Participants With ITPA Genotype rs1127354 by Incidence of Hemoglobin Drop During Prior Treatment and HCV RNA Genotype

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype and hematology data were obtained from medical records. Participants with a history of a hemoglobin level less than 10 g/dL or a drop of more than 3 g/dL at any time during prior treatment for CHC were recorded as 'yes' for this finding.

Measure: Number of Participants With ITPA Genotype rs7270101 by Incidence of Hemoglobin Drop During Prior Treatment and HCV RNA Genotype

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records. Past medication use was obtained from medical records and/or participant interview at the Study Visit. Participants with a history of erythropoietin use during prior treatment for CHC were recorded as 'yes' for this finding.

Measure: Number of Participants With ITPA Genotype rs1127354 by Erythropoietin Use During Prior Treatment and HCV RNA Genotype

Time: Study Visit 1

Description: Participants underwent blood sampling at the Study Visit to determine ITPA genotype. HCV RNA genotype was obtained from medical records. Past medication use was obtained from medical records and/or participant interview at the Study Visit. Participants with a history of erythropoietin use during prior treatment for CHC were recorded as 'yes' for this finding.

Measure: Number of Participants With ITPA Genotype rs7270101 by Erythropoietin Use During Prior Treatment and HCV RNA Genotype

Time: Study Visit 1

15 Cross-sectional Multicenter Study Evaluating the IL28B Polymorphism in Patients With HBeAg-negative Chronic Hepatitis B Treated With Pegylated Interferon Alfa-2a in the Course of Peg.Be.Liver Study

This cross-sectional multicenter study will evaluate the IL28B polymorphism in patients with HBeAg-negative chronic hepatitis B treated with Pegasys (peginterferon alfa-2a) in the predecessor ML18253 study. The study consists of a single visit where eligible patients will undergo a blood test for IL28B genotyping, with a phone follow-up 7 days after the visit.

NCT01697501
Conditions
  1. Hepatitis B, Chronic
Interventions
  1. Other: Interleukin 28B testing
MeSH:Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis
HPO:Hepatitis

Percentage of Participants With Sustained Viral Response (SVR) Defined as HBV DNA ≤ 2000 IU/ml at IL28B Genotype rs12979860 at End of Follow-up (EoF).

Percentage of Participants With HBV DNA ≤ 2000 IU/ml at IL28B Genotype rs12979860 at End of Treatment (EoT).

Percentage of Participants With HBsAg < 0.05 IU/ml at IL28B Genotype rs12979860 at EoT and EoF.

Percentage of Participants With HBsAg ≤ 10 IU/ml at IL28B Genotype rs12979860 at EoT and EoF.

Primary Outcomes

Measure: Percentage of Participants With Sustained Viral Response (SVR) Defined as HBV DNA ≤ 2000 IU/ml at IL28B Genotype rs12979860 at End of Follow-up (EoF)

Time: EoF, as defined in the predecessor study, was at 48 weeks after the end of treatment.

Measure: Percentage of Participants With SVR Defined as HBV DNA ≤ 2000 IU/ml at IL28B Genotype rs8099917 at EoF

Time: EoF

Secondary Outcomes

Measure: Percentage of Participants With HBV DNA ≤ 2000 IU/ml at IL28B Genotype rs12979860 at End of Treatment (EoT)

Time: EoT, as defined in the predecessor study, was at Week 48 or Week 96

Measure: Percentage of Participants With HBV DNA ≤ 2000 IU/ml at IL28B Genotype rs8099917 at EoT

Time: EoT

Measure: Percentage of Participants With HBsAg < 0.05 IU/ml at IL28B Genotype rs12979860 at EoT and EoF

Time: EoT and EoF

Measure: Percentage of Participants With HBsAg < 0.05 IU/ml at IL28B Genotype rs8099917 at EoT and EoF

Time: EoT and EoF

Measure: Percentage of Participants With HBsAg ≤ 10 IU/ml at IL28B Genotype rs12979860 at EoT and EoF

Time: EoT and EoF

Measure: Percentage of Participants With HBsAg ≤ 10 IU/ml at IL28B Genotype rs8099917 at EoT and EoF

Time: EoT and EoF

16 A Phase 3 Evaluation of Daclatasvir in Combination With Peginterferon Lambda-1a and Ribavirin (RBV) or Telaprevir in Combination With Peginterferon Alfa-2a and RBV in Patients With Chronic Hepatitis C Genotype 1b Who Are Treatment naïve or Prior Relapsers to Alfa/RBV Therapy (the STRUCTURE Study)

The purpose of this study is to determine if treatment with Pegylated Interferon Lambda-1a, given in combination with Ribavirin and Daclatasvir for 24 weeks, is as safe and effective as the standard treatment with Pegylated Interferon Alfa-2a + Ribavirin + Telaprevir in subjects who are infected with Chronic Hepatitis C virus genotype 1b and have never received any prior anti-HCV treatment, or who have relapsed after an initial, successful treatment with Pegylated Interferon Alfa + Ribavirin

NCT01718158
Conditions
  1. Hepatitis C
Interventions
  1. Biological: Peginterferon Lambda-1a
  2. Biological: Peginterferon Alfa-2a
  3. Drug: Ribavirin
  4. Drug: Daclatasvir
  5. Drug: Telaprevir
MeSH:Hepatitis C Hepatitis
HPO:Hepatitis

Association of Single nucleotide polymorphism (SNPs) in Interleukin 28B (IL28B) (including rs12979860) or equilibrative nucleoside transporter 1 (ENT1) with clinical responses.

Primary Outcomes

Measure: Proportion of subjects with Sustained Virologic Response at post-treatment follow-up Week 12 (SVR12)

Time: Post treatment follow-up Week 12

Secondary Outcomes

Measure: Proportion of subjects who achieve SVR12 in treatment-naive subjects

Time: Post treatment follow-up Week 12

Measure: Proportion of subjects with rash related dermatologic events

Time: Up to 12 weeks of treatment

Description: Treatment emergent cytopenic abnormalities [anemia as defined by Hemoglobin (Hb) < 10 g/dL, and/or neutropenia as defined by absolute neutrophil count (ANC) < 750/mm3, and or thrombocytopenia as defined by platelets < 50,000/mm3]

Measure: Proportion of subjects who develop treatment emergent cytopenic abnormalities

Time: Up to 48 Weeks

Measure: Proportion of subjects with on-treatment interferon (IFN) associated flu like/musculoskeletal symptoms

Time: Up to 48 Weeks

Description: SVR24 = Sustained virologic response at post treatment follow-up Week 24

Measure: Proportion of subjects who achieve SVR24 [Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Lower limit of quantitation (LLOQ)] at post-treatment follow-up Week 24

Time: Post treatment follow-up Week 24

Measure: Proportion of subjects with adverse events (AEs), Serious adverse events (SAEs), dose reductions, and discontinuations due to AEs through end of follow-up

Time: Maximum of 72 weeks

Measure: Proportion of subjects who achieve SVR12 with a 24-week treatment regimen

Time: Post treatment follow-up Week 12

Measure: Proportion of subjects who achieve Extended rapid virologic response (eRVR) (HCV RNA < LLOQ target not detected at Weeks 4 and 12 of treatment)

Time: Weeks 4 and 12 of treatment

Measure: Patient Health Questionnaire-9 (PHQ-9) score through end of follow-up

Time: Maximum of 72 weeks

Measure: Proportion of subjects with treatment emergent laboratory abnormalities by toxicity grade through End of treatment (EOT)

Time: Maximum of 72 weeks

Description: Psychiatric symptoms (depression, irritability or insomnia)

Measure: Proportion of subjects with the following on-treatment interferon-associated neuropsychiatric symptoms through EOT

Time: Maximum of 48 weeks

Description: For each SNP in each candidate gene, allele and genotype frequencies will be summarized by treatment regimen

Measure: Association of Single nucleotide polymorphism (SNPs) in Interleukin 28B (IL28B) (including rs12979860) or equilibrative nucleoside transporter 1 (ENT1) with clinical responses

Time: Post-treatment follow-up Week 12

Measure: Resistant variants associated with virologic failure through end of follow-up

Time: Maximum of 72 weeks

17 Influence of IL28B Genetic Variation on the Phenotype Infection of HTLV-1

Only 5 to 10% of patients infected with HTLV-1 develop a disease related to infection. The two most serious diseases are adult T-cell leukemia (ATL) and Tropical spastic paraparesis /HTLV-I-associated myelopathy (TSP / HAM). Factors influencing the development of TSP / HAM in the individual HTLV-1 are not yet completely understood. Patients TSP / HAM have a HTLV-1 proviral load (amount of virus) that is 6-10 times higher than seropositive asymptomatic. Various studies have shown that the development of TSP / HAM in the subject HTLV-1 and its rapid evolution is partly attributed to the failure of the immune system that regulates viral replication and expression. It has recently been shown that different versions of Single Nucleotide (human leukocyte antigen) rs12979860, located upstream of the gene for Interleukin 28B (IL28B), influenced the severity of infection with hepatitis C and effectiveness of treatment. By analogy with hepatitis C, a Spanish (Treviño et al., 2012) examined this SNP(single nucleotide polymorphism) in 12 patients TSP / HAM and 29 asymptomatic HIV-positive. CT or TT genotype was statistically more frequent in the group TSP / HAM than in asymptomatic patients (80% versus 20%) and was associated with HTLV-1 proviral load higher. We propose a broader group of patients in our population and Afro-Caribbean, to confirm the results of the latter study was conducted in a predominantly Latin American population.

NCT01754311
Conditions
  1. HTLV-I Infections
MeSH:Infection Communicable Diseases HTLV-I Infections

It has recently been shown that different versions of Single Nucleotide (human leukocyte antigen) rs12979860, located upstream of the gene for Interleukin 28B (IL28B), influenced the severity of infection with hepatitis C and effectiveness of treatment.

Primary Outcomes

Description: The participants will be followed until the end of the study ( with an expected average of 30 days after the inclusion). Explenations : each participant will have a blood sample who will be performed at the recruitement day (for génetics analysis) . After this first visit (recuitement visit) , each participant will have to perform an appointement with the ophtalmologic département ( recuperate datas about the presence or not of an uveitis and a keratoconjunctivitis)

Measure: Presence of CT or TT allele for each participant

Time: 30 days

18 Study of Parameters of Early Hepatitis C Virus Dynamics for Predicting the Outcome of Standard Interferon Therapy With Chinese Cohort (Second Phase)

The purpose of this study is to validate the first round HCV early dynamics discovery within a larger population.

NCT01760148
Conditions
  1. Hepatitis C, Chronic
  2. Liver Diseases
  3. Interferon Deficiency
Interventions
  1. Drug: interferon alpha 2b
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis Liver Diseases
HPO:Abnormality of the liver Decreased liver function Elevated hepatic transaminase Hepatitis

IL28 gene polymorphism,rs8099917,rs12979860,etc.

Primary Outcomes

Description: Blood HCV RNA copies were assayed with Roche - COBAS® AmpliPrep/COBAS® TaqMan® HCV Test.

Measure: Absolute Blood HCV RNA Copies at designed time points

Time: 0hr,24hr,1wk,2wk,4wk,6wk,12wk,24wk,48wk,72wk

Secondary Outcomes

Description: IL28 gene polymorphism,rs8099917,rs12979860,etc

Measure: IL-28B polymorphism

Time: Baseline

Description: HCV NS5A is cloned into T vector and sequenced for evolutionary analysis.

Measure: HCV genotype

Time: Baseline

Description: ALT AST are assayed to detect the hepatic function.

Measure: Alanine Aminotransferase (ALT) and Aspartate transaminase (AST)

Time: Baseline,4wk,12wk,24wk,48wk

Description: Fibrosis is analyzed with Fibroscan.

Measure: Fibrosis stage

Time: Baseline,4wk,12wk,24wk,48wk

Description: The distribution and absolute count of the different types of blood cells are assayed.

Measure: Regular blood test

Time: Baseline,4wk,12wk,24wk,48wk

Description: Electrocardiography is taken to avoid severe side effects.

Measure: Electrocardiography

Time: Baseline,4wk,12wk,24wk,48wk

Description: Patients are asked whether they take alcohol or smoke cigarettes during the therapy period.

Measure: Alcohol ,smoking condition

Time: Baseline,4wk,12wk,24wk,48wk

Description: Patients will be asked about their drug usage history.

Measure: Drug abuse history

Time: Baseline

19 Prevalence of Host and Viral Genotypes in Patients With Chronic Hepatitis B and Hepatitis C Infection in India

This study will define the substantial disease burden associated with viral hepatitis in India, and provide a foundation to understand the host and viral determinants of disease pathogenesis that may ultimately impact treatment decisions and outcome

NCT01772121
Conditions
  1. Hepatitis B
  2. Hepatitis C
MeSH:Hepatitis A Hepatitis C Hepatitis B Hepatitis B, Chronic Hepatitis
HPO:Hepatitis

Observational Study on Prevalence of Host and Viral Genotypes in Chronic Hepatitis B and Hepatitis C Patients in India This study will define the substantial disease burden associated with viral hepatitis in India, and provide a foundation to understand the host and viral determinants of disease pathogenesis that may ultimately impact treatment decisions and outcome Variation in the IL28B rs12979860 SNP.

Characterize the variation in the IL28B rs12979860 SNP that exists among patients with chronic hepatitis C or chronic hepatitis B infection, in the different geographic regions of India.

Primary Outcomes

Description: Characterize the variation in the IL28B rs12979860 SNP that exists among patients with chronic hepatitis C or chronic hepatitis B infection, in the different geographic regions of India

Measure: Variation in the IL28B rs12979860 SNP

Time: One Visit

Secondary Outcomes

Description: Assess the prevalence of HBV and HCV genotypes and subtypes in different geographic regions of India

Measure: Prevelance of HBV and HCV genotypes

Time: One Visit

Description: Characterize the SNPs present in innate immune factors TLR7 (rs3853839, rs179008); TLR9 (rs41308230, rs5743844 ); RIG-I (rs11795404, rs10813831) and NOD2 (rs2067085, rs2066842), in patients with chronic hepatitis C or chronic hepatitis B in the different geographic regions of India

Measure: Characterize the SNPs present in innate immune factors toll-like receptor 7 (TLR7)

Time: One Visit

20 A Phase 3 Randomized, Double Blind, Multi-National Evaluation of Daclatasvir in Combination With Peg Interferon Alfa-2a and Ribavirin in Treatment-Naive Subjects With Chronic Hepatitis C Genotypes 1 and 4

The purpose of this study is to determine whether 24 week treatment with the Daclatasvir (DCV) in combination with Pegylated-interferon alfa 2a (pegIFNα-2a) and Ribavirin (RBV) is safe and demonstrates rate of Sustained Virologic Response at follow up week 24 (SVR24) (defined as undetectable HCV RNA at post-treatment Week 24) that are non-inferior to 48 weeks of the dual combination therapy of pegIFNα-2a/RBV in a majority of study subjects

NCT01797848
Conditions
  1. Hepatitis C
Interventions
  1. Drug: Peginterferon alfa 2a
  2. Drug: Ribavirin
  3. Drug: Placebo matching Daclatasvir
  4. Drug: Daclatasvir
MeSH:Hepatitis C Hepatitis
HPO:Hepatitis

Proportion of subjects with Sustained Virologic Response at follow up week 12 (SVR12) or SVR24 by rs12979860 Single nucleotide polymorphism (SNP) in the IL28B gene.

Primary Outcomes

Measure: Proportion of Genotype 1 subjects with SVR24, defined as HCV RNA < Limit of quantification (LOQ) at follow-up Week 24 for each cohort

Time: Week 24 post treatment follow up

Secondary Outcomes

Measure: Proportion of Genotype (GT) 4 subjects with SVR24

Time: Week 24 post treatment follow up visit

Measure: Proportion of GT 1 & 4 subjects who achieve HCV RNA < LOQ or undetectable

Time: Week 24 post treatment follow up visit and Week 48 post treatment follow up visit for subjects who achieve Virologic response [VR] (4&12)

Measure: Frequency of Serious Adverse Events (SAEs)/discontinuations due to Adverse Events (AEs)

Time: Up to 48 weeks plus 30 days

Measure: Discontinuations due to Adverse Events (AEs)

Time: Up to 48 weeks plus 7 days

Measure: Proportion of subjects with Sustained Virologic Response at follow up week 12 (SVR12) or SVR24 by rs12979860 Single nucleotide polymorphism (SNP) in the IL28B gene

Time: Up to 72 weeks

21 Phase 2a Study of Boceprevir for the Treatment of Genotype 6 Hepatitis C

The purpose of this study is to evaluate the antiviral efficacy of Boceprevir-based therapy for the treatment of genotype 6 chronic hepatitis C infection. Boceprevir has recently been approved for the treatment of genotype 1 chronic hepatitis C infection. Recent in vitro studies suggest similar efficacy against genotype 6 chronic hepatitis C infection. The investigators therefore hypothesise that: i) Boceprevir is a potent inhibitor of genotype 6 hepatitis C replication in vivo. ii) Boceprevir in combination with pegylated interferon-alpha and ribavirin for 24 weeks will cure a high proportion of patients chronically infected with genotype 6 chronic hepatitis C infection.

NCT01949168
Conditions
  1. Chronic Hepatitis C
Interventions
  1. Drug: Victrelis® (boceprevir) 800mg by mouth, TID (200 mg tablets)
  2. Drug: Peg-Intron® (peginterferon-α-2b), 1.5ug/kg sc injection
  3. Drug: Rebetol® (ribavirin), 1000/1200mg by mouth daily
MeSH:Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

- IL28B C/C genotype (rs12979860) - Per local standard practice, documented results of one of the following: - A liver biopsy within 24 months prior to or during screening demonstrating the absence of cirrhosis, e.g., a METAVIR Score of 3 or less, Ishak score of 4 or less; or - A screening FibroTest score of ≤ 0.72 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) ≤ 2; or - A screening FibroScan result of < 9.6 kPa.

- Subjects must have the following laboratory parameters at Screening: - ALT ≤ 10 × the upper limit of normal (ULN) - AST ≤ 10 × ULN - Hemoglobin ≥ 12 g/dL - White blood cell count ≥ 2,500 cells/μL - Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 - Platelets ≥ 90,000/mm3 - Prothrombin time ≤ 1.5 × ULN - Albumin > 3 g/dL - Direct (conjugated) bilirubin < ULN - Thyroid stimulating hormone (TSH) ≤ ULN - Creatinine clearance (CLcr) ≥ 50 mL/min, as calculated by the Cockcroft-Gault equation Exclusion Criteria: - Non-genotype 6 HCV infection, or evidence of mixed genotype HCV infection - IL28B C/T or T/T polymorphism (rs12979860) - Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis, e.g., a Metavir Score of >3 or Ishak score of > 4. - Exceed defined thresholds for key laboratory parameters at Screening.

All patients will be of Asian background, will be non-cirrhotic, and will carry a "good response" IL28B genotype (C/C for rs12979860).

Primary Outcomes

Description: Determined by plasma HCV RNA quantification at frequent time points - baseline, day 1, 2, 3, 4 and 5

Measure: Early viral kinetics

Time: Day 5

Secondary Outcomes

Description: Percentage of patients with undetectable plasma HCV RNA) at different time-points

Measure: Rates of virological response

Time: Day 3, 5, week 2, week 4, week 12 and end of treatment (week 24 or week 48)

Description: Patients in Arm A and B randomised to received boceprevir-based triple therapy who achieve an undetectable HCV PCR at week 4 and week 20 are eligible for 24 weeks of therapy, vs. 48 weeks of therapy

Measure: Number of patients eligible for Response Guided Therapy

Time: Week 4 and week 20

Description: Defined by an increase in HCV RNA > 1 log10 IU/mL from nadir, or HCV RNA increase to > 100 IU/mL in patients who had previously reached an undetectable HCV RNA, and confirmed by 2 consecutive samples < 4 weeks apart.

Measure: Rates of virological breakthrough

Time: Week 4, week 20, week 24, week 48, week 60

Description: SVR 12 - Number of patients who achieve an undetectable HCV PCR 12-weeks post treatment Relapse - Number of patients who have an undetectable HCV PCR at the end of treatment but detectable HCV PCR 12-weeks post treatment

Measure: Rates of SVR12 and relapse

Time: Week 48 and Week 60

Measure: Rates of anaemia on treatment

Time: Day 0, 1, 2, 3, 4, 5, then monthly up to week 48 of treatment

22 A Phase 3 Evaluation of a Daclatasvir/Asunaprevir/BMS-791325 Fixed Dose Combination in Subjects With Genotype 1 Chronic Hepatitis C and Compensated Cirrhosis

To demonstrate the effectiveness of DCV 3DAA fixed dose combination with or without Ribavirin in treatment naive cirrhotic subjects.

NCT01973049
Conditions
  1. Hepatitis C
Interventions
  1. Drug: Daclatasvir
  2. Drug: Asunaprevir
  3. Drug: BMS-791325
  4. Drug: Ribavirin
  5. Drug: Placebo matching Ribavirin
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

Proportion of subjects in each arm achieving SVR12 associated with IL28B rs12979860 single nucleotide polymorphism(SNP) status (CC genotype or non-CC genotype).

Primary Outcomes

Description: SVR12 is defined as Hepatitis C virus ribonucleic acid (HCV RNA) < Limit of Quantification (LOQ) target detected or target not detected (LOQ TD/TND)

Measure: Proportion of treated subjects in each of the naive arms with sustained virologic response (SVR12)

Time: Post treatment 12 week

Secondary Outcomes

Measure: Proportion of treated subjects in each of the experienced arms with SVR12

Time: Post treatment 12 Week

Measure: Proportion of subjects in each arm who achieve HCV RNA < LOQ TD/TND

Time: Weeks: 1, 2, 4, 6, 8, and 12; Post treatment Weeks 4 (SVR4), 8 (SVR8) and 24 (SVR24)

Measure: Proportion of subjects in each arm who achieve HCV RNA < LOQ TND

Time: Weeks: 1, 2, 4, 6, 8, and 12; Post treatment Weeks 4 (SVR4), 8 (SVR8), 12 (SVR12) and 24 (SVR24)

Measure: Safety as measured by frequency of Serious Adverse Events(SAEs)and discontinuations due to Adverse Events(AEs)

Time: Up to end of treatment (week 12) + 7 days

Measure: Proportion of subjects with anemia defined as Hg < 10 g/dL on-treatment and Hg ≥ 10 g/dL at baseline in each arm within each cohort

Time: Up to end of treatment (week 12) + 7 days

Measure: Differences in rates of selected Grade 3 - 4 laboratory test result abnormalities

Time: Up to end of treatment (week 12) + 7 days

Measure: Proportion of subjects achieving SVR12 associated with HCV geno subtype 1a vs 1b

Time: Post treatment 12 Week

Measure: Proportion of subjects in each arm achieving SVR12 associated with IL28B rs12979860 single nucleotide polymorphism(SNP) status (CC genotype or non-CC genotype)

Time: Post treatment 12 Week

23 A Phase 3 Evaluation of a Daclatasvir/Asunaprevir/BMS-791325 Fixed Dose Combination in Non-cirrhotic Subjects With Genotype 1 Chronic Hepatitis C

To demonstrate the effectiveness of DCV 3DAA fixed dose regimen in treatment naive and treatment experienced non-cirrhotic subjects

NCT01979939
Conditions
  1. Hepatitis C
Interventions
  1. Drug: DCV/ASV/BMS-791325
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

Proportion of subjects in each cohort achieving SVR12 associated with IL28B rs12979860 single nucleotide polymorphism (SNP) status (CC genotype or non-CC genotype).

Primary Outcomes

Description: SVR12 is defined as HCV ribonucleic acid (RNA) < limit of quantitation (LOQ) target detected or target not detected (LOQ TD/TND) at post treatment Week 12

Measure: Proportion of treated subjects in the naive cohort with sustained virologic response (SVR) 12

Time: Post-Treatment Week 12

Secondary Outcomes

Measure: Proportion of subjects in the experienced cohort with SVR12

Time: Follow up Week 12

Measure: Proportion of subjects in each cohort who achieve HCV RNA Time: On-treatment Weeks: 1, 2, 4, 6, 8, and 12; post treatment Weeks 4 (SVR4), 8 (SVR8) and 24 (SVR24)

Measure: Proportion of subjects in each cohort who achieve HCV RNA Time: On-treatment Weeks: 1, 2, 4, 6, 8, and 12; post treatment weeks 4, 8, 12 and 24

Measure: Safety measured by frequency of serious AEs (SAEs) and discontinuations due to adverse events (AEs) through the end of treatment in each cohort

Time: Up to post treatment week 4 (±7 days)

Measure: Proportion of anemia defined as Hg <10 g/dL on-treatment and Hg ≥10 g/dL at baseline , in each cohort

Time: Up to post treatment week 4 (±7 days)

Measure: Rates of selected grade 3-4 lab abnormalities (hematologic and liver function) in each cohort

Time: Up to post treatment week 4 (±7 days)

Measure: Proportion of subjects in each cohort achieving SVR12 associated with HCV geno subtype 1a vs 1b

Time: Post treatment week 12

Measure: Proportion of subjects in each cohort achieving SVR12 associated with IL28B rs12979860 single nucleotide polymorphism (SNP) status (CC genotype or non-CC genotype)

Time: Post treatment week 12

Measure: Proportion of subjects in each cohort achieving SVR12 associated with stage of liver fibrosis

Time: Post treatment week 12

24 A Phase 3, Open-Label Study With Daclatasvir And Asunaprevir (DUAL) for Subjects With Genotype 1b Chronic Hepatitis C (HCV) Infection Who Are Intolerant or Ineligible to Interferon Alfa Therapies With or Without Ribavirin

Patients with chronic hepatitis genotype 1b, who are intolerant or ineligible to Interferon alfa therapy with or without Ribavirin, will be treated for 24 weeks with Daclatasvir (DCV) Dual regimen (= Daclatasvir + Asunaprevir) and followed for an additional 24 weeks post-treatment in order to determine the safety and efficacy of the DCV DUAL regimen

NCT01995266
Conditions
  1. Hepatitis C
Interventions
  1. Drug: Asunaprevir
  2. Drug: Daclatasvir
MeSH:Hepatitis C Hepatitis
HPO:Hepatitis

An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, or a congenital anomaly, or a medically important event.. Percentage of Participants With SVR24 by the rs12979860 Single Nucleotide Polymorphisms (SNP) in the IL 28B Gene at Post-Treatment Follow-up Week 24.

Primary Outcomes

Description: SVR was defined as Hepatitis C Virus ribonucleic acid (HCV RNA) < lower limit of quantitation (LLOQ) target detected (TD) or not detected (TND) at post-treatment follow-up Week 24.

Measure: Percentage of Participants With Sustained Virologic Response (SVR) at Post-Treatment Follow-up Week 24 (SVR24)

Time: 24 Weeks after treatment discontinuation (Follow-up Week 24)

Secondary Outcomes

Description: SVR12 was defined as HCV RNA < LLOQ target detected or not detected at post-treatment follow-up Week 12. For SVR12, missing HCV RNA data at follow-up Week 12 was imputed using the Next Value Carried Backwards (NVCB) approach.

Measure: Percentage of Participants With Sustained Virologic Response (SVR) at Post-Treatment Follow-up Week 12 (SVR12)

Time: 12 Weeks after treatment discontinuation (Follow-up Week 12)

Description: An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, or a congenital anomaly, or a medically important event.

Measure: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Death, and AEs Leading to Discontinuation

Time: 7 days after treatment discontinuation

Description: Participants categorized into three genotypes based on SNPs in the IL28B gene were assessed for SVR24, defined as response in which hepatitis C virus RNA levels below lower limit of quantitation or below target detected or target not detected at follow-up Week 24.

Measure: Percentage of Participants With SVR24 by the rs12979860 Single Nucleotide Polymorphisms (SNP) in the IL 28B Gene at Post-Treatment Follow-up Week 24

Time: 24 Weeks after treatment discontinuation (Follow-up Week 24)

Description: Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0. The lower and upper limits of quantitation (LOQs) of the assay for HCV GT-1 were 25 IU/mL and 3.91 X10^8 IU/mL, respectively; the limit of detection was ~ 10 IU/mL

Measure: Percentage of Participants With HCV RNA< LLOQ Target Not Detected at the End of Treatment (Week 24)

Time: Week 24 (End-of Treatment)

Description: RVR was defined as HCV RNA < LLOQ, target not detected at treatment Week 4.

Measure: Number of Participants With Rapid Virologic Response (RVR)

Time: Treatment Week 4

Description: cEVR was defined as HCV RNA < LLOQ, target not detected at treatment Week 12.

Measure: Percentage of Participants With Complete Early Virologic Response (cEVR)

Time: Treatment Week 12

Description: eRVR was defined as HCV RNA < LLOQ, target not detected at treatment Weeks 4 and 12.

Measure: Number of Participants With Extended Rapid Virologic Response (eRVR)

Time: Treatment Week 4 and Week 12

Description: Antiviral efficacy is measured by the number of participants with HCV RNA< LLOQ (lower limit of quantification), TD (target detected) or TND (target not detected) at End of Treatment (Week 24)

Measure: Number of Participants With HCV RNA < LLOQ Target Detected or Not Detected at the End of Treatment (Week 24)

Time: Week 24 (End-of Treatment)

Description: VR was defined as HCV RNA < LLOQ, target detected or not detected at specific time points (Week 4 and Week 12)

Measure: Number of Participants With Virologic Response (VR) at Treatment Week 4 and 12

Time: Treatment Week 4 and 12

25 Efficacy of Pentoxyfylline Addition to a Treatment Scheme Based on Interferon Alpha and Ribavirin on Hepatitis C Virus Coinfected HIV Patients, Considering Interleukin 28B Polymorphism rs12979860

Current Hepatitis C virus (HCV) treatment consists of the combination of interferon alpha 2a (IFN-alpha 2a) plus ribavirin (RBV) and it provides sustained virologic responses (SVR) on 54 to 56% on HCV monoinfected patients and this response is even lower on HIV-HCV coinfected patients. A previous study on HCV monoinfected patients showed that the addition of pentoxyfylline (PTX) to a treatment scheme based on interferon-alfa and ribavirin increased SVR on 25%, although it is not known if the same effect is to be obtained in HCV-HIV coinfected patients. On the other hand, other factors such as host genetics, have proved to influence treatment response on HCV infected patients. The best described genetic factor so far is the interleukin 28B (IL28B) polymorphism rs12979860, where a cytosine-cytosine (CC) genotype provides an almost twice increase on SVR than the rest of the genotypes. Therefore, this is a randomized, double blind study to assess the efficacy of pentoxyfylline addition to a treatment scheme based on interferon-alfa and ribavirin in chronic HCV genotype 1, co-infected HIV-1 positive subjects, considering the IL28B polymorphism rs12979860. HIV-HCV coinfected subjects currently receiving Highly active antiretroviral therapy (HAART), with at least 8 months on undetectable HIV viral load and T helper cells count of 200 or higher will be included. Patients will be randomized on one of two groups: - Group A: IFN alpha 2a + RBV + PTX - Group B: IFN alpha 2a + RBV + placebo Patients will be followed for primary outcome during 72 (for rapid responders) or 96 weeks (for non rapid responses). Outcome measures will be the following: - SVR rate 24 weeks after the end of treatment - Grade of Hepatic fibrosis from baseline to the end of treatment, measured by transient elastography and the AST to platelet ratio index (APRI index) - IL28B rs12979860 genotype The study hypothesis is that the addition of PTX to a treatment scheme based on IFN-alfa2a and RBV in chronic HCV genotype 1, co-infected HIV-1 positive subjects will improve SVR rate and fibrosis progression irrespectively of IL28B rs12979860 genotype.

NCT02008214
Conditions
  1. Hepacivirus
  2. HIV Infections
Interventions
  1. Drug: Pentoxifylline
  2. Drug: Placebo
MeSH:Hepatitis C

Efficacy of Pentoxyfylline Addition to a Treatment Scheme Based on Interferon Alpha and Ribavirin on Hepatitis C Virus Coinfected HIV Patients, Considering Interleukin 28B Polymorphism rs12979860.

The best described genetic factor so far is the interleukin 28B (IL28B) polymorphism rs12979860, where a cytosine-cytosine (CC) genotype provides an almost twice increase on SVR than the rest of the genotypes.

Therefore, this is a randomized, double blind study to assess the efficacy of pentoxyfylline addition to a treatment scheme based on interferon-alfa and ribavirin in chronic HCV genotype 1, co-infected HIV-1 positive subjects, considering the IL28B polymorphism rs12979860.

Outcome measures will be the following: - SVR rate 24 weeks after the end of treatment - Grade of Hepatic fibrosis from baseline to the end of treatment, measured by transient elastography and the AST to platelet ratio index (APRI index) - IL28B rs12979860 genotype The study hypothesis is that the addition of PTX to a treatment scheme based on IFN-alfa2a and RBV in chronic HCV genotype 1, co-infected HIV-1 positive subjects will improve SVR rate and fibrosis progression irrespectively of IL28B rs12979860 genotype.

Percentage of patients with CC genotype on the IL28B rs12979860 polymorphism.

Primary Outcomes

Description: Primary objective: is to evaluate sustained virologic response at post treatment week 24 following treatment with IFNalpha 2a/RBV/PTX with genotype 1 chronic HCV infection + HIV infection

Measure: sustained virologic rate 24 weeks post treatment with IFNalpha 2a/RBV/PTX with genotype 1 chronic HCV infection + HIV infection

Time: SVR rate at 24 weeks after the end of therapy

Secondary Outcomes

Description: The liver stiffness (hepatic fibrosis) will be measured by transient elastography and the APRI index on the baseline visit and then at the follow up visit after treatment, which will be after 72 weeks, for patients that turn out to be quick responders; or 96 weeks, for patients that turn out to be non-quick responders.

Measure: grade of hepatic fibrosis

Time: Baseline and week 72 (for quick responders) or week 96 (for non-quick responders)

Description: secondary objective (2): Evaluate rapid virologic response (RVR) and extended rapid virologic response (eRVR)

Measure: rapid virologic response (RVR) and extended rapid virologic response (eRVR) rates

Time: RVR at week 4 and eRVR at week 48 post treatment

Other Outcomes

Description: We will compare the percentage of patients with CC genotype among patients that achieved sustained virologic response and those who did not achieved it. This is to confirm if the intervention provides a beneficial effect, irrespectively of host genetic factors.

Measure: Percentage of patients with CC genotype on the IL28B rs12979860 polymorphism

Time: week 72

26 A Randomized, Single Blind, Dose Escalation, Placebo-Controlled Study to Assess the Safety, Pharmacokinetics, and Antiviral Activity of Repeat Doses of GSK2878175 in Subjects With Chronic Hepatitis C.

GSK2878175 is a site IV NS5B non-nucleoside inhibitor (NNI) being developed for the treatment of chronic hepatitis C virus (HCV) infection. The purpose of this study is to investigate the effects of GSK2878175, at different doses in men and women infected with chronic hepatitis C virus. The study will investigate how much of the drug gets into the blood stream and how long the body takes to get rid of it. The study will also investigate if GSK2878175 has any important side effects. The study will also measure what effect GSK2878175 has on the hepatitis C virus infection after taking the study medication for 2 days. Approximately 44 people will take part in this study. Depending on the type of chronic hepatitis C infection a subject will be enrolled into 1 of 4 groups randomly. Each group will participate in one dosing session. One dosing session consists of GSK2878175 or a placebo (sugar pill) given once per day for 2 days. Group A, B, and C is made up of 8 participants per group. In each of these groups 6 participants will receive GSK2878175 and 2 participants will receive placebo. Group D is made up of 20 participants. 15 participants will receive GSK2878175 and 5 participants will receive placebo. The treatment groups will be dosed in sequence. Group A will be the first to take the study medication, then Group B, and so on. The plan is to dose subjects in Group A with 10 mg, Group B with 30 mg, Group C with 60 mg, and Group D with 60 mg of GSK2878175 or placebo. The next treatment group's actual dose will be decided after looking at the results from the previous group. The doses may therefore be higher or lower than planned depending on the previous group's results. The number of participants enrolled in the next group may also change depending on the results from the previous group.

NCT02014571
Conditions
  1. Hepatitis C, Chronic
Interventions
  1. Drug: GSK2878175
  2. Drug: Placebo
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic
HPO:Chronic active hepatitis Chronic hepatitis Hepatitis

Antiviral activity as assessed by HCV RNA maximum change.. HCV RNA change from baseline to nadir (maximum change) in CHC subjects.. Antiviral activity as assessed by Time course of HCV viral load.. Time course of HCV viral load at baseline, during, and after dosing with GSK2878175.. Viral quasi-species population.. Sequence analysis of the viral quasispecies population as appropriate before and after a repeat dose.. IL28B rs12979860 status on GSK2878175 pharmacokinetics.. Determination of IL28B status (C/C versus carriage of the T allele) status on GSK2878175 pharmacokinetics or exposure-response relationship.. Exposure-response relationships for various safety parameters, if appropriate.. Correlation between PK parameters and various safety parameters, if appropriate.. Exposure-response relationship for antiviral effect.. Correlation between PK parameters and changes in HCV RNA viral load at 24, 48 and 72 hours after the first dose.. Inclusion Criteria: - Has chronic genotype 1 (subtypes 1a or 1b) or genotype 2 or genotype 3 or genotype 4 (as assessed by VERSANT® HCV Genotype assay 2.0 (LiPA); VERSANT is a registered trademark of the Siemens Healthcare company.)

Primary Outcomes

Description: AEs will be collected from the start of Study Treatment and until 14 days post last-dose (at follow up).

Measure: Safety as assessed by the collection of adverse events (AEs).

Time: Screening to 14 days post last-dose

Description: Absolute values and changes over time of hematology, clinical chemistry, urinalysis, vital signs (blood pressure [BP], FSH/Estradiol (Women), Urine β-hCG (Women) temperature, and heart rate), 12 LED ECG, and Holter monitoring, ECG intervals, ECG rhythm, and telemetry will be measured. Telemetry is the continuous monitoring of a subject's heart rate and rhythm from a remote location. Pulmonary function testing includes a group of tests that measure how well the lung is functioning.

Measure: Safety as assessed by hematology, clinical chemistry, urinalysis, vital signs, electrocardiogram (ECG) intervals, ECG rhythm telemetry, pulmonary function tests, respiratory rate and lung auscultation.

Time: Pre-dose to 14 days post last-dose

Description: PK parameters include: AUC (0-24), Tmax, Cmax,C24, t1/2, tlag, CL/F for Day 1

Measure: Composite of PK parameters (Day 1) following repeat dose administration of GSK2878175.

Time: Pre Dose, 0.5hr, 1.5hr, 4hr, 6hr, 12hr

Description: PK parameters include: AUC (0-t), Ct, Cmax, tmax, t1/2, CL/F for Day 2.

Measure: Composite of PK parameters (Day 2) following repeat dose administration of GSK2878175.

Time: Day 2 Pre Doseand Post Day 1 Dose at 24hr, 24.5hr, 25.5hr, 28hr, 30hr, 33hr, 36hr, 48hr, 72hr, 96hr, 144hr, 192hr, 240hr and 360hr

Description: HCV RNA viral load reduction from baseline at the 24 hr, 48 hr, and 72 hr timepoints during dosing of GSK2878175 in HCV subjects

Measure: Antiviral activity as assessed by HCV RNA viral load.

Time: Baseline, 24 hr, 48 hr, and 72 hr

Description: HCV RNA change from baseline to nadir (maximum change) in CHC subjects.

Measure: Antiviral activity as assessed by HCV RNA maximum change.

Time: Pre-dose to 14 days post last-dose.

Description: Time course of HCV viral load at baseline, during, and after dosing with GSK2878175.

Measure: Antiviral activity as assessed by Time course of HCV viral load.

Time: Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 7, Day 9, Day 11, and Day 16 (Follow Up Visit)

Secondary Outcomes

Description: Sequence analysis of the viral quasispecies population as appropriate before and after a repeat dose.

Measure: Viral quasi-species population.

Time: Pre Dose and 12hr on Day 1 and at 24hr, 30hr, 36hr, 48hr, 72hr, 96hr, 144hr, 192hr, 240hr and 360hr Post 1st Dose

Description: Determination of IL28B status (C/C versus carriage of the T allele) status on GSK2878175 pharmacokinetics or exposure-response relationship.

Measure: IL28B rs12979860 status on GSK2878175 pharmacokinetics.

Time: Day 1 Pre Dose.

Description: Correlation between PK parameters and various safety parameters, if appropriate.

Measure: Exposure-response relationships for various safety parameters, if appropriate.

Time: Pre-dose to 14 days post last-dose

Description: Correlation between PK parameters and changes in HCV RNA viral load at 24, 48 and 72 hours after the first dose.

Measure: Exposure-response relationship for antiviral effect.

Time: 24, 48 and 72 hours after the first dose.

27 A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naïve and Treatment-experienced Chronic Hepatitis C (Genotype 1, 2, 3, 4, 5, or 6) Subjects Coinfected With Human Immunodeficiency Virus (HIV)

A study of the efficacy and safety of the combination of daclatasvir and sofosbuvir in the treatment of hepatitis C virus and HIV coinfection.

NCT02032888
Conditions
  1. Hepatitis C
Interventions
  1. Drug: Daclatasvir
  2. Drug: Sofosbuvir
MeSH:Hepatitis A Hepatitis C Hepatitis
HPO:Hepatitis

HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.. Percentage of Participants With CC or Non-CC Genotype at the IL28B rs12979860 Single Nucleotide Polymorphisms Who Achieved Sustained Virologic Response at Follow-up Week 12 (SVR12).

Primary Outcomes

Description: SVR12 was defined as HCV RNA Measure: Percentage of Genotype 1 Hepatitis C Virus (HCV)-Infected Treatment-naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)

Time: At follow-up Week 12

Secondary Outcomes

Description: SVR12 was defined as HCV RNA Measure: Percentage of Hepatitis C Virus (HCV)/HIV-coinfected Treatment-naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)

Time: At follow-up Week 12

Description: SVR12 was defined as HCV RNA Measure: Percentage of Hepatitis C Virus (HCV)/HIV-coinfected Treatment-experienced Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)

Time: At follow-up Week 12

Description: SVR12 was defined as HCV RNA levels Measure: Percentage of Participants of All Genotypes Coinfected With Hepatitis C Virus (HCV)/HIV Who Achieved Sustained Virologic Response Rate at Follow-up Week 12 (SVR12)

Time: At follow-up Week 12

Description: Participants with hepatitis C virus CV) levels to be Measure: Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels to be Time: Week 1, 2, 4, 6, 8, 12, End of treatment, and follow-up Week 4 and 24


Description: Participants with HCV RNA levels Measure: Percentage of Participants Coinfected With Hepatitis C Virus/HIV Who Achieved HCV RNA Levels Time: At Weeks 1, 2, 4, 6, 8, and 12 and at End of Treatment


Description: SVR is defined as hepatitis C virus RNA Measure: Percentage of Participants With CC or Non-CC Genotype at the IL28B rs12979860 Single Nucleotide Polymorphisms Who Achieved Sustained Virologic Response at Follow-up Week 12 (SVR12)

Time: At Follow-up Week 12

Description: AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.

Measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Interruption or Discontinuation, Treatment-related AEs/SAEs and Grade 3 to 4 AEs/SAEs and Who Died During Treatment Period

Time: AEs: Day 1 to 7 days after last dose of study treatment (8 weeks or 12 weeks). SAEs: Day 1 to 30 days after last dose of study treatment (8 weeks or 12 weeks)

Description: AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.

Measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-related AEs/SAEs, Grade 3 to 4 AEs/SAEs, and Who Died During Follow-up Period

Time: AEs: Day 1 of follow-up period (Week 9 or Week 13) to 7 days after end of 24 weeks follow-up period. SAEs: Day 1 of follow-up period (Week 9 or Week 13) to 30 days after end of 24 weeks follow-up period.

Description: Grade 3-4 abnormalities on laboratory test results were defined as: International normalized ratio as 2.1-3.0*upper limit of normal (ULN) for grade 3 and >3.0*ULN for grade 4. Leukocytes as 1.0*10^9-1.5*10^9/L for grade 3 and <1.0*10^9/L for grade 4. Aspartate aminotransferase as 5.1-10.0*ULN for grade 3 and >10.0*ULN for grade 4. Bilirubin (total) as 2.6-5.0*ULN for grade 3 and >5.0*ULN for grade 4. Lipase (total) as 3.1-5.0*ULN for grade 3 and >5.0*ULN for grade 4. Alanine aminotransferase as 5.1-10.0*ULN for grade 3 and >10.0*ULN for grade 4.

Measure: Number of Participants With Treatment-emergent Grade 3-4 Abnormalities on Laboratory Test Results

Time: From screening up to week 24 of post treatment follow--up

28 A Phase 3 Evaluation of Daclatasvir and Sofosbuvir in Treatment Naive and Treatment Experienced Subjects With Genotype 3 Chronic Hepatitis C Infection

To study the combination of Daclatasvir and Sofosbuvir for the treatment of hepatitis C virus (HCV) Genotype 3 infection

NCT02032901
Conditions
  1. Hepatitis C
Interventions
  1. Drug: Daclatasvir
  2. Drug: Sofosbuvir
MeSH:Hepatitis C Hepatitis
HPO:Hepatitis

Presence or absence of cirrhosis was determined at baseline and follow-up Week 12 in the participants to evaluate the post-treatment relapse.. Percentage of Participants With CC or Non-CC Genotype at the IL28B rs12979860 Single Nucleotide Polymorphisms (SNPs) Who Achieved Sustained Virologic Response After 12 Weeks of Follow-up (SVR12).

Primary Outcomes

Description: SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation ie., 25 IU/mL, TD or TND at follow-up Week 12. HCV RNA levels were measured by the Roche Cobas® TaqMan® HCV Test version 2.0 from the central laboratory.

Measure: Percentage of Treatment-Naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) Target Detected (TD) or Target Not Detected (TND)

Time: Week 12 (Follow-up period)

Description: SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation ie., 25 IU/mL, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

Measure: Percentage of Treatment-Experienced Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) Target Detected (TD) or Target Not Detected (TND)

Time: Week 12 (Follow-up period)

Secondary Outcomes

Description: RVR was defined as hepatitis C virus RNA levels to be < lower limit of quantitation ie, 25 IU/mL TND at Week 4. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

Measure: Percentage of Participants With Rapid Virologic Response at Week 4 (RVR) Target Not Detected (TND)

Time: Week 4

Description: cEVR was defined as hepatitis C virus RNA levels to be < lower limit of quantitation ie, 25 IU/mL TND at Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

Measure: Percentage of Participants With Complete Early Virologic Response (cEVR) Target Not Detected (TND)

Time: Week 12

Description: EOTR were defined as hepatitis C virus RNA levels to be < lower limit of quantitation ie, 25 IU/mL TND at end of treatment. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

Measure: Percentage of Participants With End of Treatment Response (EOTR) Target Not Detected (TND)

Time: Up to the end of treatment (up to 24 weeks)

Description: Percentage of participants who achieved HCV RNA Measure: Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Less Than the Lower Limit of Quantitation (LLOQ) - Target Not Detected (TND)

Time: Week 1, 2, 6, 8 (treatment period)

Description: Percentage of participants who achieved HCV RNA Measure: Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Less Than the Lower Limit of Quantitation (LLOQ)- Target Detected (TD) or Target Not Detected (TND)

Time: Week 1, 2, 4, 6, 8, 12, End of treatment (treatment period), Week 4 (follow-up period), Week 24 (follow-up period)

Description: SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation ie. 25 IU/mL, target detected or target not detected at follow-up Week 12. Cirrhosis was considered a negative predictor of SVR in participants treated with an interferon formulation or ribavirin. Presence or absence of cirrhosis was determined at baseline and follow-up Week 12 in the participants to evaluate the post-treatment relapse.

Measure: Percentage of Participants With Or Without Cirrhosis at Baseline Who Achieved Sustained Virologic Response at Follow-up Week 12 (SVR12)

Time: Baseline, Week 12 (Follow-up period)

Description: Participants categorized into 2 genotypes (CC and non-CC) based on SNPs in the IL28B gene were assessed for SVR12, defined as response in which hepatitis C virus (HCV) RNA levels below lower limit of quantitation (LLOQ) below target detected or target not detected at follow-up Week 12 (LLOQ: 25 IU/mL). HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

Measure: Percentage of Participants With CC or Non-CC Genotype at the IL28B rs12979860 Single Nucleotide Polymorphisms (SNPs) Who Achieved Sustained Virologic Response After 12 Weeks of Follow-up (SVR12)

Time: Week 12 (Follow-up period)

Description: AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization.

Measure: Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs)

Time: From Day 1 first dose to last dose plus 7 days

29 Security and Efficacy of Triple Therapy Including Direct-Acting Antivirals Against Chronic Hepatitis C Infection In HIV-Coinfected Patients In Real-Life Conditions: The Prospective HEPAVIR Cohort.

The purpose of this study is to evaluate the efficacy and tolerability of DAA-based regimens in the clinical practice in HIV/HCV-coinfected patients. Hypothesis: The efficacy and tolerability of DAA-based regimens in the clinical practice is different to what is observed in clinical trials in HIV/HCV-coinfected patients.

NCT02057003
Conditions
  1. Hepatitis C, Chronic
  2. Human Immunodeficiency Virus
Interventions
  1. Drug: DAA against HCV
MeSH:Hepatitis A Hepatitis C Acquired Immunodeficiency Syndrome HIV Infections Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

Definition of hepatic fibrosis: - advanced fibrosis: F3 as determined by liver biopsy or 11 kilopascals as determined by transient elastometry - cirrhosis: F4 as determined by liver biopsy or 14.6 kilopascals as determined by transient elastometry Variables collected within in the cohort: - primary outcome variable: SVR (efficacy study) and % of patients who discontinued therapy due to adverse events (safety study) - epidemiological variable: age, sex, interleukin 28B rs12979860 genotype - variables related to hepatitis C virus-infection: infection route, genotype, grade of hepatic fibrosis and method used for its determination, baseline Child-Pough-Index, previous hepatic decompensations - treatment-related variables: previous response to treatment, doses and dose reductions/discontinuations of peg-IFN, RBV and the DAA(s), overall severe adverse events, adverse events that occur in more than 5% of the patients, hepatic decompensations, deaths, HCV viral load at baseline and at each visit - variables related to HIV-infection: Centers for Disease Control and Prevention (CDC) category, HIV viral load, cluster of differentiation 4 (CD4) cell count, antiretroviral regimen - analytical variables: aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelets, leucocytes, low-density lipoprotein cholesterol, bilirubin, gamma-glutamyltransferase (GGT), alkaline phosphatase, - clinical variables: alcohol intake Quality assurance and data checks: Data will be obtained from controlled databases at the participating centers.

Primary Outcomes

Description: Achievement of SVR to DAA-based therapy in the clinical practice in patients with chronic hepatitis C and HIV coinfection.

Measure: Number of patients who achieve SVR to DAA-based therapy as measure of efficacy

Time: 18 months

Description: Development of severe adverse events related to DAA-based therapy in the clinical practice in patients with chronic hepatitis C and HIV coinfection.

Measure: Number of patients who develop severe adverse events as measure of safety

Time: 18 months

Secondary Outcomes

Description: In order to compare TVR- and BOC-based therapy, the numbers of patients who achieve SVR to DAA-based therapy will be analyzed.

Measure: Number of patients who achieve SVR to a BOC-based regimen as compared to numbers of patients who achieve SVR to a TVR-based regimen.

Time: 18 months

Measure: Number of patients who reach undetectable HCV-RNA at week 4 of PI-based therapy as a measure of on-treatment response to therapy.

Time: 18 months

Description: In order to compare TVR- and BOC-based therapy, the numbers of patients who develop adverse events during either treatment will be analyzed.

Measure: Number of patients who develop adverse events during a BOC-based regimen as compared to numbers of patients who develop adverse events during a TVR-based regimen.

Time: 18 months

Description: The numbers of patients who achieve SVR to DAA-based therapy in absence of interferon will be analyzed.

Measure: Number of patients who achieve SVR to an interferon-free regimen.

Time: 36 weeks

30 A Phase 3 Study of a Daclatasvir/Asunaprevir/BMS-791325 Fixed Dose Combination (FDC) in Subjects With Chronic Hepatitis C Genotype 1

To demonstrate the effectiveness of Daclatasvir (DCV) 3 Direct Acting Antivirals (DAA) fixed dose combination in Genotype 1 Chronic Hepatitis C subjects.

NCT02170727
Conditions
  1. Hepatitis C Virus
Interventions
  1. Drug: DCV/ASV/BMS-791325
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

Percentage of subjects in each cohort who achieved SVR12 associated with HCV genotype subtype 1a vs 1b were reported.. Proportion of Participants Who Achieved SVR12 Associated With IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) Status (CC Genotype or Non CC Genotype).

Proportion of Participants who Achieved SVR12 Associated with IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) status (CC genotype or non CC genotype) were reported.. Proportion of Cirrhotic and Non Cirrhotic Participants Who Achieved SVR12.

Primary Outcomes

Description: Percentage of Participants with SVR12 in the naive cohort, defined as HCV RNA < LLOQ target detected (TD) or target not detected (TND) (LOQ TD/TND) at post-treatment follow-up Week 12.

Measure: Percentage of Participants With Sustained Virologic Response 12 (SVR12) in the Naive Cohort

Time: Post treatment Week 12

Secondary Outcomes

Description: Percentage of treated participants with SVR12 in the IFNα experienced cohort, defined as HCV RNA < LLOQ target detected or target not detected (LLOQ TD/TND).

Measure: Percentage of Participants With SVR12 in the Interferon Alfa (IFN-a) Experienced Cohort

Time: Post treatment Week 12

Description: Percentage of Participants with hepatitis C virus(HCV) ribonucleic acid (RNA) < lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) were presented at treatment Weeks 1, 2, 4, 6, 8, 12, EOT, and follow-up Weeks 4 (SVR4), 8 (SVR8), and 24 (SVR24).

Measure: Percentage of Participants Who Achieved HCV RNA < LLOQ TD/TND

Time: On-treatment Weeks: 1, 2, 4, 6, 8, and 12; post treatment Weeks 4 (SVR4), 8 (SVR8), 24 (SVR24) and EOT (end of treatment)

Description: Percentage of treated participants with HCV RNA < LLOQ, TND (target not detected) were presented at treatment Weeks 1, 2, 4, 6, 8, 12, at both Weeks 4 and 12, EOT, and follow-up Weeks 4, 8, 12 and 24.

Measure: Percentage of Participants Who Achieved HCV RNA < LLOQ TND

Time: On-treatment Weeks: 1, 2, 4, 6, 8, and 12 and post treatment weeks 4, 8, 12, 24 and EOT (end of treatment)

Description: SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect.

Measure: Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment

Time: Up to post treatment week 4

Description: Anemia was defined as hemoglobin < 10 g/dL on-treatment for subjects who had hemoglobin >= 10 g/dL at baseline.

Measure: Percentage of Participants With Anemia Defined as Hb < 10 g/dL On-treatment Who Had Hb >=10 g/dL at Baseline

Time: Up to post treatment week 4

Description: Percentage of subjects in each cohort who achieved SVR12 associated with HCV genotype subtype 1a vs 1b were reported.

Measure: Percentage of Participants Who Achieved SVR12 Associated With Hepatitis C Virus (HCV) Genotype Subtype 1a vs 1b

Time: Post treatment week 12

Description: Proportion of Participants who Achieved SVR12 Associated with IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) status (CC genotype or non CC genotype) were reported.

Measure: Proportion of Participants Who Achieved SVR12 Associated With IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) Status (CC Genotype or Non CC Genotype)

Time: Post treatment Week 12

Description: Proportion of Cirrhotic and Non Cirrhotic Participants who Achieved SVR12 were reported.

Measure: Proportion of Cirrhotic and Non Cirrhotic Participants Who Achieved SVR12

Time: Post treatment Week 12

Description: Rates of selected Grade 3 - 4 laboratory abnormalities on treatment in each cohort was estimated

Measure: Number of Participants With Selected Grade 3/4 Laboratory Abnormalities

Time: Post treatment week 4

Description: Subgroup analysis of on-treatment safety with non-cirrhosis vs cirrhosis, as measured by the frequency of SAEs, discontinuations due to AEs was conducted.

Measure: Number of Participants With/Without Cirrhosis as Measured by SAEs and Discontinuations Due to AEs

Time: Up to post treatment week 4

Description: Subgroup analysis of on-treatment safety with non-cirrhosis vs cirrhosis, as measured by the selected Grade 3 - 4 laboratory abnormalities (including hematologic and liver function, based on DAIDS criteria) was conducted.

Measure: Number of Participants With/Without Cirrhosis as Measured by Selected Grade 3-4 Laboratory Abnormalities

Time: Up to post treatment week 4

31 Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis C (FOURward Study)

The purpose of the study is to determine whether the combination of Daclatasvir (DCV), Asunaprevir (ASV), BMS-791325 and Sofosbuvir is effective and safe in treating Hepatitis-C virus.

NCT02175966
Conditions
  1. Hepatitis C
Interventions
  1. Drug: DCV/ASV/BMS-791325
  2. Drug: Ribavirin
  3. Drug: Sofosbuvir
  4. Drug: Peginterferon α-2a
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype).

Percentage of Participants who Achieved SVR12 Associated with IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) status (CC genotype or non CC genotype) were reported..

Primary Outcomes

Description: SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) < lower limit of quantitation (LLOQ) target detected (TD) or not detected (TND) at post-treatment follow-up Week 12. Imputed SVR12 was based on Next Value Carried Backwards approach.

Measure: Percentage of Participants With Sustained Virologic Response 12 (SVR12)

Time: 12 Weeks after treatment discontinuation (Follow-up Week 12)

Description: SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect.

Measure: Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment

Time: From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)

Description: Grade 3/4 laboratory abnormalities (hematology, electrolyte, lipase, liver function, metabolic, renal function, urinalysis). The Week 24 data set was used to evaluate the Week-24 on-treatment safety. The cumulative data set was used to evaluate the safety while on treatment. Common Terminology Criteria for Adverse Events v3.0 (CTCAE) Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death.

Measure: Number of Participants With Selected Grade 3/4 Laboratory Abnormalities

Time: From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months)

Secondary Outcomes

Description: EOTR was defined as HCV RNA less than the lower limit of quantitation, target detected or not detected at end of treatment.

Measure: Percentage of Participants With End of Treatment Response (EOTR)

Time: End of the treatment

Description: Percentage of Participants with hepatitis C virus(HCV) ribonucleic acid (RNA) < lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) were presented at treatment Weeks 1, 2, 4, 6, and follow-up Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24).

Measure: Percentage of Participants Who Achieved HCV RNA Time: Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24)

Description: Percentage of Participants with hepatitis C virus(HCV) ribonucleic acid (RNA) < lower limit of quantitation (LLOQ), target not detected (TND) were presented at treatment Weeks 1, 2, 4, 6, and follow-up Weeks 2 (SVR2), 4 (SVR4), and 24 (SVR24).

Measure: Percentage of Participants Who Achieved HCV RNA < LLOQ TND

Time: Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2, 4, 12 and 24

Description: Percentage of Participants who Achieved SVR12 Associated with HCV geno subtype 1a or 1b

Measure: Percentage of Participants Who Achieved SVR12 Associated With HCV Geno Subtype 1a vs 1b

Time: Post-treatment Week 12

Description: Percentage of Participants who Achieved SVR12 Associated with IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) status (CC genotype or non CC genotype) were reported.

Measure: Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype)

Time: Post-treatment Week 12

32 Hepatitis B and Hepatitis C as Risk Factors for Hepatocellular Carcinoma in African and Asian Immigrants: Role of Viral Genetics and the Immune Response

The prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in the United States (US) is relatively low. However, immigrant populations in the US from Asia and sub-Saharan Africa have substantially higher prevalence than the general population and are consequently at a significant risk for hepatocellular carcinoma (HCC). Indeed, the age-adjusted incidence rates for HCC in the US have tripled from 1975 to 2005. As the population demographics have changed, the 2000 US census estimated the number of Somalis in Minnesota at 25,000 but current estimates put the number at around 50,000 due to primary refugee arrivals as well as secondary immigration from other states. There is no available data for Somali immigrants in the US on HBV and HCV prevalence, HBV and HCV genotypes/subgenotypes, and genetic and immunologic risk factors predisposing Somalis to HBV and HCV and the subsequent development of HCC. Therefore. this study will fill these gaps in the Somali population to understand the relative importance of HBV and HCV infections in causation of HCC. Besides Somalis, Minnesota is also home to large other African immigrant communities. According to the Minnesota Department of Health (MDH), in 2013, the highest rates of chronic HBV cases where reported among Asian or Pacific Islanders (3,638 cases per 100,000 persons) followed by Black or African Americans (2,078 cases per 100,000 persons). Additionally, Minnesota receives a large number of new refugee's resettlement. It is important to improve the identification of chronic HBV and HCV infections among Somali refugees and immigrants in Minnesota through well-designed community-wide screening efforts. Since we know that African immigration to Minnesota is the third highest in the US, this unique population might be a contributing factor to the increased burden of hepatitis and liver cancer complications in the state of Minnesota. Findings from HBV and HCV screening among Somalis suggest that other immigrant African populations from high viral hepatitis endemic regions, such Ethiopia, Liberia, and Kenya, are also at substantial risk of HBV, HCV and HCC. Unfortunately, very little research has been conducted in the US on the burden of hepatitis and liver cancer in African Immigrants from areas of high endemicity of hepatitis B and hepatitis C. Therefore, the goal of is to identify HBV and HCV and the role viral genetics and immune response among African immigrant communities from Kenya, Liberia, and Ethiopia.

NCT02366286
Conditions
  1. Hepatitis B
  2. Hepatitis C
  3. Carcinoma, Hepatocellular
MeSH:Hepatitis A Hepatitis C Hepatitis B Carcinoma Carcinoma, Hepatocellular Hepatitis
HPO:Carcinoma Hepatitis Hepatocellular carcinoma

In the following Sub-Aims we will: - measure the expression levels of toll-like receptors (in monocytes) of the host innate immune response to assess whether the expression of TLR differs between those exposed to HBV vs HCV - measure the circulating Tregs of the host adaptive immune response to determine whether the abundance of Treg differs between those exposed to HBV vs HCV Specific Aim 3: To determine whether genetic variation of IL28B (assessed by single nucleotide polymorphisms, rs12979860 and others) is associated with HCV treatment outcome in Somalis.

Primary Outcomes

Measure: Number of subjects who test positive for markers of Hepatitis B Virus infection (HBsAg, HBcAb, HBsAb)

Time: 2 Years

Measure: Number of subjects who test positive for markers of Hepatitis C Virus infection (anti-HCV infection)

Time: 2 years

Measure: Rate of HBV vaccination in subjects with negative HBV serology

Time: 2 Years

Secondary Outcomes

Measure: Incidence of HCC over the period of the study

Time: 2 Years

33 Efficacy and Safety of Sofosbuvir Plus Daclatasvir in Chinese Treatment-experienced Patients With Chronic Genotype 1b HCV Infection

For those chronic hepatitis C patients, who are interferon-ineligible or intolerant, there is a burning need for the development of pan-oral interferon-free regimen. The investigators examine the efficacy and safety of sofosbuvir, a NS5B nucleotide polymerase inhibitor and daclatasvir, an NS5A replication complex inhibitor in Chinese treatment-experienced cirrhosis patients with chronic G1b infection.

NCT02473211
Conditions
  1. Chronic Hepatitis C Infection
Interventions
  1. Drug: Sofosbuvir
  2. Drug: Daclatasvir
MeSH:Infection Hepatitis C Hepatitis C, Chronic

At baseline, liver stiffness measurement (LSM) using transient elastography (FibroScan®) is used to assess liver fibrosis and the single nucleotide polymorphism ofinterferon-λ 3 (IL-28, rs12979860, C or T) and IFLN4 (ss469415590, TT or ΔG) is determined.

Primary Outcomes

Description: SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) (15 IU/ml) 12 weeks following the last dose of study drug

Measure: Proportion of participants with sustained virologic response 12 weeks after the end of treatment (SVR12)

Time: Post treatment Week 12

34 A Phase 3 Evaluation of Daclatasvir and Asunaprevir in Treatment-naive Subjects With Chronic Hepatitis C Genotype 1b Infection

The purpose of this study is to determine whether a regimen consisting of daclatasvir and asunaprevir is effective in treatment-naive patients with chronic hepatitis genotype 1b infection.

NCT02496078
Conditions
  1. Hepatitis C
Interventions
  1. Drug: Daclatasvir
  2. Drug: Asunaprevir
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

Proportion of subjects with SVR12 by the rs12979860 single nucleotide polymorphism (SNP) in the interleukin (IL) -28B gene for each cohort.

Primary Outcomes

Description: HCV RNA < Lower limit of quantitation (LLOQ) target detected (TD) or target not detected (TND) at follow-up Week 12

Measure: Proportion of treated subjects randomized to Active Dual therapy with Sustained Virologic Response (SVR12)

Time: Post-treatment Week 12

Secondary Outcomes

Measure: Proportion of subjects with anemia on active Dual therapy

Time: Post-treatment Week 12

Measure: Proportion of subjects with neutropenia on active Dual therapy

Time: Post-treatment Week 12

Measure: Proportion of subjects with thrombocytopenia on active Dual therapy

Time: Post-treatment Week 12

Measure: On treatment safety, as measured by frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs)

Time: Post-treatment week 12

Measure: Differences in rates of selected Grade 3-4 laboratory abnormalities for hematology between treatments (DCV + Asunaprevir (ASV) vs PBO)

Time: first 12 weeks on treatment

Measure: Differences in rates of selected Grade 3-4 laboratory abnormalities for liver function between treatments (DCV + Asunaprevir (ASV) vs PBO)

Time: first 12 weeks on treatment

Measure: Proportion of subjects with SVR12 by the rs12979860 single nucleotide polymorphism (SNP) in the interleukin (IL) -28B gene for each cohort

Time: Post-treatment visit week 12

Measure: Proportion of subjects with hepatitis C virus (HCV) RNA < LLOQ-TD/TND in each arm at various intervals after the initiation of active Dual therapy

Time: post-treatment visit Week 24

Measure: Proportion of subjects who achieve HCV RNA < LLOQ-TND at each arm at various intervals after the initiation of active Dual therapy

Time: post-treatment visit Week 24

Measure: Proportion of treated subjects with SVR12 for subjects randomized to placebo

Time: Post-treatment visit week 12

35 Impact of IL-28B rs12979860 and rs4803217 Gene Polymorphisms Associated With miRNAs Deregulation on HCV-related Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide as well as in Egypt. Despite improvements in HCC therapy, the prognosis for HCC patients remains poor. Today molecular, genomic and epigenomic aberrations in tumors are being deeply investigated. Many biomarkers were associated to HCC onset, and they could be useful for clinicians, but all show some limitations and no one is so early to predict the HCC onset. It is estimated that 51.5% of HCC cases can be attributed to HCV infection. Moreover, there is a large occult reservoir of HCV caused chronic liver disease in approximately 9 % in the Egyptian with estimated 6 million HCV chronic infections and estimated 150 000 new infections per year. Among them, we have to mention the polymorphism of IL28B gene rs12979860 C/T. and rs 4803217. The IL-28B gene encodes interferon-lambda 3 (IFN-λ3), which belongs to the type III IFN family. IFN-λ interacts with a transmembrane receptor inducing a potent antiviral response. In experimental model of HCV type III IFN was able to inhibit viral replication. IL-28B polymorphisms are linked to the efficiency of the inflammatory process during HCV infection, and to the mechanisms that HCV adopts to escape by innate and adaptive immunity. During the last years, a number of studies have assessed the association between the IL-28B polymorphisms and risk of HCC and liver cirrhosis (LC) occurrence in various populations; however, results obtained are still inconclusive. Interestingly, some polymorphisms located at the 3' untranslated region (UTR) of IL28B, e.g. rs 4803217, seem to interfere with the binding of miRNA, to date recognized as important post-transcriptional regulators. In the last years miRNAs acquired a growing relevance as potential biomarkers for several diseases including cancer, and many researches are focusing on understanding their role in cancer. Thus the objectives of the current proposal are to determine through investigating a cohort of 405 patients, whether IL28B rs12979860 and rs4803217 polymorphisms are associated to the risk of HCC in chronic hepatitis C (CHC) patients and, above all, to identify their role as predictor marker of HCC in CHC, when associated to miRNAs modulation. Data obtained by our work could be helpful in HCC diagnosis, thus leading to the improvement of the patients prognosis. The proposed activities are going to be implemented through a partnership us as Egyptian Liver Research Institute and Hospital (ELRIAH)- Dakhlya- Egypt and Non- Egyptian Partners.

NCT02507882
Conditions
  1. HCV Infection ( Genotype 4)
Interventions
  1. Biological: IL28B Polymorphism
  2. Biological: miRNA quantification
MeSH:Hepatitis C Carcinoma, Hepatocellular
HPO:Hepatocellular carcinoma

Impact of IL-28B rs12979860 and rs4803217 Gene Polymorphisms Associated With miRNAs Deregulation on HCV-related Hepatocellular Carcinoma.

Impact of IL-28B rs12979860 and rs4803217 Gene Polymorphisms Associated With miRNAs Deregulation on HCV-related Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide as well as in Egypt.

Among them, we have to mention the polymorphism of IL28B gene rs12979860 C/T. and rs 4803217.

Thus the objectives of the current proposal are to determine through investigating a cohort of 405 patients, whether IL28B rs12979860 and rs4803217 polymorphisms are associated to the risk of HCC in chronic hepatitis C (CHC) patients and, above all, to identify their role as predictor marker of HCC in CHC, when associated to miRNAs modulation.

IL-28B rs12979860 and rs4803217 Genotype evaluation.

rs12979860 C/T and rs4803217.

Objectives The overall goal is to investigate the Impact of IL-28B rs12979860 and rs4803217 gene polymorphisms associated with miRNAs deregulation on HCV-related hepatocellular carcinoma Specific Objectives: 1.

3. IL28B Polymorphism: SNP rs12979860 and 4803217 will be determined in whole blood by allelic discrimination using specific probes by real time PCR.

IL28B SNPs comparisons will be done by stratifying patients according to rs12979860CC and rs12979860CT/TT genotypes and 4803217 Analysis miRNA PCR Array will be done by specific Data Analysis Software specifically supplied by Quiagen.

Primary Outcomes

Description: Different types of IL28B and their relation to the progressiveness of HCC

Measure: IL-28B rs12979860 and rs4803217 Genotype evaluation

Time: 6 months to 1 year from the start of the study

Measure: Specific miRNA levels and their association with degree of fibrosis, cirrhosis and HCC

Time: 1 to 2 years from the start of the study

36 Cytomegalovirus Reactivation in Non Immunocompromised Patients Undergoing Cardiac Surgery

We hypothesized that the stress of cardiac surgery and cardiopulmonary bypass can cause reactivation of a latent CMV infection and that reactivation might be more prevalent in patients with complicated post-operative course. The study aims are: - To study whether cardiac surgery is a trigger for latent CMV reactivation and to compare reactivation rate between sub groups of patient with complicated post-operative course and non complicated post operative course. - To study the relationship between expression IL28 SNP rs12979860 and the risk of CMV replication in the non immunocompromised patient undergoing cardiac surgery.

NCT02527291
Conditions
  1. Cardiac Surgery
Interventions
  1. Other: Blood test

- To study the relationship between expression IL28 SNP rs12979860 and the risk of CMV replication in the non immunocompromised patient undergoing cardiac surgery.

The relationship between expression IL28 SNP rs12979860 and the risk of CMV replication in the non immunocompromised patient undergoing cardiac surgery.. null.

Primary Outcomes

Measure: The cumulative of death, prolonged hospitalization, prolonged post-operative mechanical ventilation and prolonged use of vasopressors

Time: 12 months

Measure: CMV reactivation: viral load elevation comparing to the baseline level prior to surgery

Time: 12 months

Secondary Outcomes

Measure: The relationship between expression IL28 SNP rs12979860 and the risk of CMV replication in the non immunocompromised patient undergoing cardiac surgery.

Time: 12 months

37 Impact of Interleukin 28B (rs12979860) Genotype on Virological Responses in Chronic Hepatitis C Treatment

Objective: Pegulated Interferon α2 plus ribavirin is a treatment of choice in patients with chronic hepatitis C infection. This study was conducted to find out the frequency of different IL-28B (rs12979860) genotypes in patients with chronic hepatitis C (HCV genotype type 2 & 3) infection treated with Pegulated Interferon α2 plus ribavirin and to evaluate the role of IL-28B genotypes in achieving Sustained Virological Response (SVR). Methods: In this non-randomized observational study, ninety eight (98) patients with diagnosis of chronic hepatitis C were included. In all patients, Peg-IFN plus Ribavirin were given in standard doses for 24 weeks. End treatment response, sustained virological response, and relapse rate were the primary endpoints of this study. Analysis of IL28B (rs12979860) polymorphism (CC, CT and TT) was performed by PCR-RFLP protocol.

NCT03090035
Conditions
  1. Hepatitis C
  2. Hepatitis C Relapse
Interventions
  1. Drug: Pegylated Interferon α2
  2. Drug: Ribavirin
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

Impact of Interleukin 28B (rs12979860) Genotype on Virological Responses in Chronic Hepatitis C Treatment.

Impact of Interleukin 28B (rs12979860) Genotype on Virological Responses Chronic Hepatitis C Treatment Objective: Pegulated Interferon α2 plus ribavirin is a treatment of choice in patients with chronic hepatitis C infection.

This study was conducted to find out the frequency of different IL-28B (rs12979860) genotypes in patients with chronic hepatitis C (HCV genotype type 2 & 3) infection treated with Pegulated Interferon α2 plus ribavirin and to evaluate the role of IL-28B genotypes in achieving Sustained Virological Response (SVR).

Analysis of IL28B (rs12979860) polymorphism (CC, CT and TT) was performed by PCR-RFLP protocol.

The aim of present study was to find out the frequency of different IL28B (rs12979860) genotypes in patients with chronic hepatitis C (genotype type 2 or 3) infection treated with Pegulated Interferon α2 plus ribavirin and to evaluate the role of IL-28B genotypes in achieving Sustained Virological Response (SVR).

Analysis of IL28B (rs12979860) polymorphism (CC, CT and TT) was performed by PCR restriction fragment length polymorphism (RFLP) assay protocol.

Primary Outcomes

Description: Treatment Success rate (End Treatment Response) was noted to check the adequency of treatment

Measure: Treatment Success rate

Time: after 24 weeks of treatment

Secondary Outcomes

Description: Sustained Virological Response was noted to check treatment success after extended period

Measure: Sustained Virological Response

Time: After 48 weeks of treament

Description: Relapse Rate to check re-occurrence of Hepatitis infection

Measure: Relapse Rate

Time: After 48 weeks of treament

38 Prevalence of IL28B Polymorphism in Hepatitis C Patients in Singapore and Its Effect on the Outcome of Hepatitis C Treatment

Response to peginterferon and ribavirin treatment in hepatitis C (HCV) depends on viral and host factors. Single nucleotide polypmorphisms (SNP) near to IL28B gene (especially at rs12979860 and rs8099917) are strongly associated with the response to treatment in HCV genotype 1 infection, less so in HCV genotype 2/3 infection. CC genotype in rs12979860 and TT genotype at rs8099917 are associated with good treatment outcome. Asian populations have high prevalence of CC genotype in other studies, which can explain relatively good response to peginterferon/ ribavirin in genotype 1 infection in Asians compared with Caucasians.

NCT03415009
Conditions
  1. Hepatitis C
MeSH:Hepatitis A Hepatitis C Hepatitis
HPO:Hepatitis

Single nucleotide polypmorphisms (SNP) near to IL28B gene (especially at rs12979860 and rs8099917) are strongly associated with the response to treatment in HCV genotype 1 infection, less so in HCV genotype 2/3 infection.

CC genotype in rs12979860 and TT genotype at rs8099917 are associated with good treatment outcome.

Primary Outcomes

Measure: the prevalence of genetic variants for IL28B SNPs (rs 12979860 and rs 8099917) in HCV patients in Singapore.

Time: Baseline

Secondary Outcomes

Measure: The distribution of the different SNP variants in different ethnic groups (Chinese, Malay, Indian and others)

Time: Baseline

Description: To study the correlation between genetic variants and treatment response

Measure: The association of the genetic variants and the treatment response in patients receiving peg-interferon/ ribavirin therapy.

Time: Baseline


HPO Nodes


HP:0001392: Abnormality of the liver
Genes 1400
TNFSF11 UBR1 TRNK B3GLCT PEX3 NDUFS4 SCYL1 TREX1 CASP8 IARS1 SLC25A13 TRAPPC11 ABCC2 ALG9 GTF2IRD1 CAVIN1 EPB41 CD247 RASA2 APC NHLRC2 PEX3 TSHR NGLY1 ARVCF FANCM UCP2 ND1 ANTXR1 SDHD NELFA RREB1 NLRP3 HPGD CD70 LETM1 KIF3B IFT172 NPHP3 ARSA ASS1 TCF4 WDR35 SHPK RFX6 PSAP PEX11B PEX6 ERCC4 PAX4 SETBP1 HBB APOB RIT1 CEP164 ZAP70 ZIC3 STK11 STN1 GPC1 CYP27A1 GNPTAB DYNC2H1 PEX11B PDGFRL PEX1 PKLR GALK1 AP1S1 TTC7A BRIP1 TREX1 HSD3B7 PLIN1 FDX2 CD81 TNFRSF13B SEC24C POLG2 UROS KLF11 IL36RN PIK3CA CLDN1 SLC37A4 PIGA CD96 CYBA ERCC8 AKT2 FANCG FOXF1 TET2 NDUFV2 GLIS3 DLD PEX2 GNS AKT2 SLC25A20 RRAS2 CASP10 TNPO3 XRCC4 PC NEUROD1 WDR19 NOD2 CEP290 PTRH2 CCDC115 C8ORF37 CPOX SLC13A5 NSMCE2 HAMP VPS45 FBP1 SPTB PRKCD SPECC1L CBS DNAJB11 COG8 HOXD13 RNU4ATAC KMT2E PKD2 TTC21B PKD2 PDX1 NPHP1 AKR1D1 IFT27 CBL PHKG2 PEX19 USB1 NLRP3 SPTB TMEM70 PEX26 CR2 PEX12 SEC63 SPOP ACVRL1 FAH STX11 HNF4A SDHA NEK1 MADD ERCC8 PDGFB FANCL CPLX1 FAS ALDOB PSAP TCIRG1 CALR PEX16 ACADVL RINT1 FAN1 TET2 TKT RFX5 SLC2A1 VPS33A HMGCL MYRF RFT1 SLC4A1 XK NGLY1 DLL4 PCSK1 MSH2 C11ORF95 MVK MCM4 FLI1 AGPAT2 TINF2 ARSA IYD CFTR CR2 CASK ESCO2 LRP5 AGA TRIM37 MET NLRP3 SMPD1 KRT18 FANCF IGF2R NCKAP1L WDPCP GATA6 BBS9 LACC1 ACADVL APPL1 IFT80 CPT1A PEX1 IGF2 KIF20A STAT1 DLL4 PLEKHM1 RMRP KRAS IFT140 UQCRFS1 PEX12 HNF1A PRKCSH TRNN SCO1 BTK SLC25A15 MSH6 PEX13 ERCC8 BSCL2 SLC39A4 NDUFB11 RBCK1 HNRNPA2B1 PALLD RNASEH2B UGT1A1 NDUFAF8 SLC44A1 PSMB9 CCND1 AHCY ATPAF2 SMAD4 SKIV2L SNX10 HMBS TERT ALG8 ABCC8 SC5D TMEM216 NPC1 POMC FANCI FAS SLC22A5 SCARB2 HBB HFE LDLRAP1 HADH MMAA MYBPC3 PEX6 MET NOTCH2 PEX10 CTLA4 RPGRIP1L TRIM28 NPC2 SCYL1 ALMS1 CP VCP TUFM IDUA SBDS COG6 RFXAP GPC3 B9D1 TRHR DHDDS TTC7A PEX14 CYP19A1 INTU SLCO1B3 PTEN NLRP1 TIMMDC1 BBS7 DUOX2 HNF4A COG5 LDLR MMEL1 DNASE1L3 RASGRP1 FANCA DLD COG4 MARS1 PCK2 SOS1 KRT18 IARS1 ENG SCNN1B TYMP HNF1A DHFR GPI LPIN2 TGFB1 MAN2B1 KCNQ1OT1 TTC21B NPM1 NDUFS4 SLC2A1 HNF1A TSHB IL18BP ANK1 CTLA4 MMUT PCSK9 CEP19 KLF1 POLG2 IL21R APC IRF5 IL17RC SAR1B TERT PIGM PEX1 ERBB3 LYZ DYNC2H1 ATAD3A DNAJC21 CTNNB1 MPI PEX14 CFTR PSAP IFT80 RHBDF2 PPARG RTL1 TGFB1 MKS1 DDOST HBA2 TRNE TSFM NDUFB9 NPHP3 EWSR1 GCGR POU6F2 PLPBP PMM2 IDUA SFTPA2 IRAK4 APC HBG2 SLC29A3 RAG2 PEX10 JAK1 GBA MMUT JMJD1C SLC30A10 CPT2 NDUFS6 PALB2 GALT OCLN ETFDH TBX1 WDR19 FLNC NCF4 FASLG COX4I2 IFT172 RFXANK PEX12 PIEZO1 EPB41 BCS1L GBA CORIN ENG SPTA1 PTPN3 PHKB AGA RAG2 TPI1 FECH ALAS2 IL17F MADD MKKS FANCC PYGL LIMK1 PEPD BLK AMACR MCCC1 TWNK MKS1 CNOT1 APC ATP7B NCF1 CD3D NDUFAF1 IL2RB RNU4ATAC CDKN2A NDUFA6 SAA1 FARSA PMS1 IL7R RNASEH2A FAH GAA ABCB11 BRCA2 NDUFS2 TTC37 LMNA SPTA1 PKHD1 ND3 IL17RA KRAS TMEM216 KLF1 IGLL1 BRCA2 DPAGT1 SPTB IGHM PEX16 FASLG PEX10 SOX10 SLC39A8 FAM111B DNAJC19 GDF2 INSR HLA-DRB1 MRPL44 PEX13 NDUFA1 CYBB NEU1 CD3E BSCL2 ATP6AP1 MLH1 PTPRC BCHE TNNI3 GPIHBP1 SNX10 KRT8 PTPN11 CC2D2A FBP1 ACAD9 GNPTAB IDUA CTSK XPR1 ACVRL1 TFAM CYBB TFR2 POLG HADHB MTTP NRAS ARSA LPIN2 CC2D2A CLCN7 DOLK NEU1 ADA SETBP1 FANCB STAT3 ABCB4 PEX6 PEX2 PEX10 ETFB SFTPC SLX4 TSC1 SLC25A13 PGM1 A2ML1 RPGRIP1L PHKG2 HMBS MEFV GABRD ITCH BRCA2 SEMA4A PLAGL1 TRMT5 PALB2 NDUFAF2 ASXL1 ABCG5 DMPK USP18 VPS33B TMEM67 UFD1 HYMAI C1QBP AXIN1 TREX1 HNF1B HNF4A ASAH1 SLC29A3 NOTCH2 UBE2T SRP54 GBA DKC1 JAK2 TSHR TCIRG1 BBS5 POLG2 ERCC6 MMAB HBB NFKB1 IL1RN KCNQ1 TMEM126B ACADM EIF2AK3 ABCB4 DNAJC19 TALDO1 ARL6 PEX12 AP1S1 STEAP3 UNC13D PEX5 HADHA HFE SP110 NFKB2 TRAPPC11 PHKA2 ANK1 IDS CPT1A RNF43 PCCB NDUFAF4 SETD2 KCNN4 ERCC4 CTLA4 INPP5E HMGCS2 DZIP1L NEUROG3 PEX16 JAM2 COG1 POU2AF1 PEX19 DIS3L2 CD28 POLG PEX5 RHAG ADA2 BPGM UROD BCS1L RBPJ WDR19 MRPS7 HNRNPA1 BMPER CPT2 H19-ICR SLC25A13 ADAR TMEM67 MTRR GYPC MLH3 HBA2 GFM1 EFL1 TERC DDRGK1 FOS BOLA3 TF GLB1 MEG3 BBS12 DPM1 AIRE LIG4 PARN HSD3B7 ATP7B PIGS TPO BBS2 PEX11B TRIM37 GLB1 PPARG DCLRE1C SCNN1A UQCRB GPC3 CYP7B1 ALG9 NHP2 IGF2 EXTL3 MAN2B1 COMT PRKCD BLNK MYORG IL2RG OSTM1 IL7R SLC17A5 GCLC ABCG8 SMPD1 APC ETFA RHAG WT1 SPRTN LIPA RAB27A RAG2 SDHC IER3IP1 NR1H4 SMAD4 CYTB BTNL2 ADAMTSL2 INVS GDF2 PSMB4 CLCN7 FGFR2 GNE PEX6 ARHGAP31 JAK2 MS4A1 GNE G6PD BBIP1 DHCR7 MPI TINF2 INSR ERCC6 CAVIN1 ATP6AP2 LBR BBS1 IFNG KIT RRM2B LIPE HNF4A LMNA JAK3 BMP2 ABCG8 PIK3C2A LMBRD1 IFT172 PEX3 NBAS IFT140 BTK AMACR HBG1 CTBP1 LZTFL1 BTNL2 PEPD KCNJ11 GALT GAA SNX14 MFN2 SEC63 MYC ERCC6 DYNC2I1 TP53 CASR NKX2-5 BBS10 RAD51C NAB2 MPV17 TMEM67 GALE PSAP PEX13 REST TGFBR2 PRPS1 PLEKHM1 TTC8 CLIP2 ABCC8 H19 CYBC1 ELN RAG1 PKD1 NPHP1 EPB42 CLEC7A HIRA GP1BB DYNC2LI1 TCIRG1 CYP27A1 SLC26A4 PMM2 FERMT3 HSD17B4 PEX3 ELN FUCA1 EXTL3 HJV TMEM67 MYD88 AGGF1 ARSB MOGS RIPK1 KCNN4 NDUFAF5 HFE NOTCH1 PMS2 DUOXA2 FOXP3 WDR19 USP9X TRMU ND4 SDCCAG8 AP3B1 CBL APOC2 LPL CD28 PKHD1 SON LIPE PPOX TCF3 SUMF1 CA2 HESX1 CC2D2A PDGFRB CEP83 STXBP2 TARS2 GLRX5 HNF1B PCK1 IFT122 TET2 SLC40A1 BBS4 SLC7A7 ARL6 ABHD5 BCS1L STK11 PEX2 PCCA TTC37 DOCK6 DAXX INPPL1 DIS3L2 KRAS TNFRSF13C PRSS1 AP1B1 HSD17B10 SF3B1 SLC25A19 TERT DYNC2I2 TNFRSF1B FANCD2 SLC30A10 IL7R LMNA AGL GPC4 FECH H19-ICR TRNV NAGA RMND1 CIITA KIT GBA G6PC3 CEP290 PEX26 GUCY2D NDUFB10 TRMU TJP2 TMEM67 DNAJC21 PEX26 IL12RB1 SH2D1A XRCC4 SLC25A4 IDUA IL2RA ARG1 PEX19 NDUFA11 NDUFS3 MED25 GBA SLC35C1 HJV IQCB1 MRPL3 SP110 EPB42 VPS13A NAGA SERPINA1 NHP2 SLC4A1 ATP8B1 LIG4 ADK SLC25A20 RAG1 CEP55 RRAS SLC22A5 SKIV2L CLDN1 PSAP TREX1 ZAP70 ALDOB LMNA GATA2 ND2 ND5 IFIH1 IFNGR1 BRCA1 SLC7A7 NDUFS7 FGFRL1 APOE GATA6 JAM3 GCDH UGT1A1 CBS AP3D1 SOS2 ABCA1 NPHP3 TKFC FOXRED1 LIPA PEX3 CSPP1 ACAT1 PCCB CASP10 ALDH7A1 TNFRSF13C FADD BLVRA PPARG GCK KPTN MECP2 LBR AP1B1 PCCA SBDS KCNH1 SLCO1B3 MRAS MRPS28 TNFSF11 CYP7B1 DCDC2 PDGFRA PEX1 SLC25A15 NPHP3 ADA SLC20A2 LIPA PRF1 ND3 TRAF3IP1 ACAD9 GBA SLC4A1 GBA JAK2 TNFRSF11A SUMF1 GUSB CD40LG MSH2 DHCR7 LARS1 MMACHC F5 MIF GUSB ABCC2 NSD2 TRIM32 GBA LBR NCF2 MAN2B1 CEP290 FOXP3 RAC2 PKD1 TNFSF15 RELA SDHA TPP2 SDCCAG8 CIDEC RAG1 STAT6 CDKN1C IFT43 HAVCR2 HMGCL HBB SLC4A1 ACP5 XIAP RNASEH2A IL2RG ATP7A SPTB POLR3A AGPAT2 BTK CARS2 ALG13 ERCC1 ATRX TMEM231 ND1 COG7 IDUA MUC5B COG4 PRKCD NPHP4 LRRC8A RMRP SPINK1 PIEZO1 MPC1 EARS2 ABHD5 NDUFAF3 LCAT PSAP ABCA1 ABCD3 C1S CPA1 KCNJ11 LONP1 CTCF GANAB MSH6 TSC2 PEX14 DGUOK TNFSF12 TMEM107 PEX16 SLCO2A1 COG2 SDHB TRNL1 IDS CHD7 SLC37A4 BSCL2 DPM2 NAGS B2M ARSA CTNNB1 TNNT2 SRP54 CAV1 RPS20 SLCO1B1 DYNC2LI1 LYST PLIN1 CD19 HMOX1 APOA1 ADAMTS13 CCDC47 CYP7A1 ND2 SLC25A1 EIF2AK3 CPOX CPOX CIDEC ITCH APC2 SERPINA1 GPD1 PTRH2 LYRM4 GBA UGT1A1 APOE PFKM POLG TNFRSF1A SPIB CLCN7 YARS2 NSD1 NDUFS8 F5 KCNN3 LMNB2 DYNC2I1 RHAG GNMT HYOU1 TBX1 TNFSF12 EPCAM JAK2 PEX14 ATP8B1 TBL2 MLH1 AKR1D1 TBX19 ATP11C FANCE PDGFRA TGFB1 CTNS NCF2 PNPLA2 TNFRSF1B CEP120 DDRGK1 RFC2 FUCA1 SLCO1B1 PSTPIP1 NPHP3 SLC40A1 CTRC UGT1A1 NDUFS1 TMEM165 RNASEH2C NSD2 TRNW LHX3 FH RRM2B NOP10 PEX5 PEX19 IL12A IL6 FLT1 CD19 SURF1 LTBP3 SMPD1 BBS1 MPV17 B9D2 BRCA1 BSCL2 MPL PSMB8 DCTN4 KRIT1 CLCA4 CTSC LRP5 PROP1 ASL CLCN7 TRIP13 SLC25A19 FCGR2A MST1 ANKS6 ALDOA TRAF3IP2 TBX1 IDS SRSF2 TRIM28 WDPCP ALG8 CD79A PIK3R1 NOP10 TRNS1 TRAF3IP1 ALG2 RAF1 SCNN1G COG6 CD79B HEXB CTSA CPT2 PRDM16 STOX1 ASAH1 SC5D NDUFS7 HK1 TALDO1 NUBPL RPGRIP1 COX15 MAGT1 PAX8 ABCA1 STEAP3 HADHA TERC PHKA2 RTEL1 INS CYBA NDUFB3 PEX12 GPC3 HADH CASR SMAD4 RASGRP1 HBB CASR GBE1 RERE DMPK ICOS FADD MAD2L2 DCDC2 PNPLA6 SKI LMNA ABCB11 EOGT WT1 SEC23B TRNW ICOS RFX5 SLC25A13 ABCB4 GLB1 DCLRE1C ALMS1 NCF1 HBG2 CYBC1 CDAN1 FGA PARS2 LRPPRC RPGRIP1L IL2RG LHX4 KCNH1 TBX19 CDIN1 ACOX1 HBB TMPRSS6 TNFRSF13B LMNA TET2 HAMP NRAS PEX26 TP53 PNPLA2 POU1F1 WRAP53 FAS ABCG8 SAMHD1 WDR35 NDUFV1 ATP7A RFXAP TMEM199 G6PC1 PEX6 CCDC28B KRAS GTF2I DGUOK HGSNAT APOA1 NHP2 TG NEK8 IFIH1 TERT RUNX1 CLPB RNASEH2C ALG1 CIITA HADHA COX14 SLC11A2 RNU4ATAC OFD1 XYLT1 WDR35 EFL1 CD27 BMPR1A PEX2 RBM8A ATP8B1 MKS1 POLD1 NSMCE2 RAD51 POMC MMUT PRKCSH HBA1 CAV1 XRCC2 ITK VHL BICC1 RECQL4 AUH ERCC6 PKLR FARSB RAB27A NAGLU CTC1 PRSS2 PEX5 SLC5A5 LYST GBA JAG1 MYPN C4B LETM1 STX1A RFWD3 APC CFTR CEP290 WHCR GPC4 ICOS RFXANK CDKN1B ERCC8 HPD CA2 ND6 ACADM PRKAR1A MLXIPL VIPAS39 LZTR1 HLA-DRB1 MPL INPP5E PAX8 CD55 HLA-DRB1 MVK DKC1 DLK1 DYNC2I2 APOE KRT8 UGT1A1 POU1F1 SGSH GPR35 BAZ1B ERCC4 NDUFAF1 FBN1 RFT1 HBA1 WT1 TERC PIK3CA GNAS ATP6V1B2 PEX1 CPT2 ATP6 COA8 ACOX1 TCTN2 GANAB TMEM67 KCNAB2 VPS33A GALNS CEL PYGL NEU1 XIAP GALM BTD PRKAR1A FGFR2 MVK