The purpose of this study is to determine the efficacy of a 12- or 24-week treatment regimen of simeprevir in combination with daclatasvir, as measured by sustain virologic response 12 (SVR12), in treatment-naive, chronic hepatitis C virus (HCV) genotype 1b-infected participants who have advanced fibrosis or compensated cirrhosis (METAVIR F3/F4).

NCT02268864

Conditions

1. Hepatitis C, Chronic

Interventions

1. Drug: Simeprevir
2. Drug: Daclatasvir

MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis

HPO:Hepatitis

For cirrhotic participants (METAVIR score F4) a biopsy performed at any previous time is acceptable - Participants who have cirrhosis must have an hepatic imaging procedure (ultrasound, computed tomography [CT] scan or magnetic resonance imaging [MRI]) within 6 months prior to the Screening visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma - Participant must have a body mass index (BMI) >= 18 Kilogram per meter^2 (kg/m^2) - Participant must be treatment naive (that is, have not received prior treatment for HCV with any approved or investigational drug) Exclusion Criteria: - Participant has co-infection with HCV of another genotype; a) Participant who has HCV genotype 1b has coinfection with HCV of a genotype other than genotype 1b - Chronic HCV genotype 1b-infected participant who has the presence of genetic variants coding for the NS5A-Y93H and/or L31M/V amino acid substitutions at Screening - Participant has evidence of current or previous episodes of hepatic decompensation (including controlled or uncontrolled ascites, bleeding varices or hepatic encephalopathy) - Participant has chronic liver disease of a non-HCV etiology (including but not limited to hemochromatosis, Wilson's disease, alfa 1-antitrypsin deficiency, cholangitis, drug- or alcohol-related liver disease, primary biliary cirrhosis) - Participant has any other uncontrolled clinically significant disease or clinically significant findings during Screening that in the opinion of the investigator could compromise the participants' safety or could interfere with the participant participating in and completing the study - Participant has coinfection with hepatitis A or hepatitis B virus (hepatitis A antibody immunoglobulin M [IgM] or hepatitis B surface antigen [HBsAg] positive at Screening) - Participant has received a solid organ transplant Inclusion Criteria: - Participant must have chronic Hepatitis C virus (HCV) genotype 1b infection confirmed at Screening - Participant must have HCV ribonucleic acid (RNA) greater than (>) 10,000 international unit per milliliter (IU/mL) at Screening - Participant must have documented fibrosis stage at Screening (or between Screening and Day 1 [baseline]). --- Y93H --- --- L31M ---

For cirrhotic participants (METAVIR score F4) a biopsy performed at any previous time is acceptable - Participants who have cirrhosis must have an hepatic imaging procedure (ultrasound, computed tomography [CT] scan or magnetic resonance imaging [MRI]) within 6 months prior to the Screening visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma - Participant must have a body mass index (BMI) >= 18 Kilogram per meter^2 (kg/m^2) - Participant must be treatment naive (that is, have not received prior treatment for HCV with any approved or investigational drug) Exclusion Criteria: - Participant has co-infection with HCV of another genotype; a) Participant who has HCV genotype 1b has coinfection with HCV of a genotype other than genotype 1b - Chronic HCV genotype 1b-infected participant who has the presence of genetic variants coding for the NS5A-Y93H and/or L31M/V amino acid substitutions at Screening - Participant has evidence of current or previous episodes of hepatic decompensation (including controlled or uncontrolled ascites, bleeding varices or hepatic encephalopathy) - Participant has chronic liver disease of a non-HCV etiology (including but not limited to hemochromatosis, Wilson's disease, alfa 1-antitrypsin deficiency, cholangitis, drug- or alcohol-related liver disease, primary biliary cirrhosis) - Participant has any other uncontrolled clinically significant disease or clinically significant findings during Screening that in the opinion of the investigator could compromise the participants' safety or could interfere with the participant participating in and completing the study - Participant has coinfection with hepatitis A or hepatitis B virus (hepatitis A antibody immunoglobulin M [IgM] or hepatitis B surface antigen [HBsAg] positive at Screening) - Participant has received a solid organ transplant Hepatitis C, Chronic Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis This is an open-label (all people know which treatment the participants receive) study to investigate the efficacy, safety and tolerability of simeprevir and daclatasvir in chronic Hepatitis (inflammation of the liver) C virus (HCV) genotype 1b infected participants who are treatment-naive. --- Y93H --- --- L31M ---

To identify side effects of Sofosbuvir/ Daclatasvir treatment regimen of chronic HCV GT-4 infection. - To assess the occurrence and the prevalence of RAVs in patients with treatment failure and relapse after sofosbuvir and daclatasvir with assessment of their types . - To examine the GT4 subtypes by phylogenetic analysis and baseline sequence variability among subtypes and their potential impact on treatment outcome and development of viral resistance in patients who received a regimen of Sofosbuvir/ Daclatasvir for treatment of chronic HCV GT-4. - To assess the differences in patient demographics across GT4 subtypes.

NCT03572140

Conditions

1. HCV

Interventions

1. Diagnostic Test: RAVS In relapsed and resistent cases

NS5A RAVs can be very common, with Y93H detected in up to 15% of the population and L31M in up to 6.3%. --- Y93H --- --- L31M ---

Chronic hepatitis C virus (HCV) infection is a major public health problem with an estimated 180 million people infected worldwide. In the United States an estimated 4.1 million people are infected and HCV is the principal cause of death from liver disease and leading indication for liver transplantation. Within HIV/HCV co-infected patients, liver disease due to Hepatitis C progresses even more rapidly. While combination of ribavirin (RBV) and pegylated interferon (PEG) in combination with boceprevir/telaprevir is the currently recommended therapy for chronic HCV infection and has superior cure rates compared to PEG+RBV alone in HCV monoinfected patients, treatment is still associated with a high incidence of adverse events (AEs), discontinuations and poor cure rates in several populations. Within the HIV/HCV co-infected population treatment for HCV remains complicated given drug interactions between anti-retrovirals and HCV protease inhibitors, in addition to the extensive side-effects due to PEG +RBV alone. Recent studies have demonstrated that the use of a combination of anti-virals which target HCV without interferon (IFN) can cure HCV, without additional toxicities. These novel therapies that do not rely on an IFN backbone may additionally enhance cure rates in HIV/HCV co-infected, a population which has historically been difficult to cure. The findings from this study will aid in the understanding of antiviral and host responses and determinants of response to an IFN free regimen in HIV/HCV co-infected patients.

NCT02124044

Conditions

1. HIV-HCV

Interventions

1. Drug: Asunaprevir and Daclatasvir
2. Drug: Asunaprevir and Daclatasvir with BMS-791325

Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson s disease, alfa-1 antitrypsin deficiency, cholangitis) 2. Positive nucleotide sequence analyses of the NS5A gene for Y93H or L31M/V polymorphisms for the 2DAA arm only. --- Y93H --- --- L31M ---

The purpose of this study is to determine whether BMS-790052 added to Peginterferon Alfa-2a and ribavirin can result in higher cure rates in patients who previously failed therapy and may have limited response to retreatment with Peginterferon Alfa-2a and ribavirin alone.

NCT01170962

Conditions

1. Hepatitis C Virus

Interventions

1. Drug: BMS-790052
2. Drug: BMS-790052
3. Drug: Placebo
4. Drug: peginterferon alfa-2a
5. Drug: ribavirin

MeSH:Hepatitis C Hepatitis

HPO:Hepatitis

Non-structural protein 5A of HCV resistance associated polymorphism in GT-1a samples included M28L/T/V, Q30H, L31M, H54Y, H58C/D/N/P/Q, E62D and Y93C.. Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures. --- M28L --- --- Q30H --- --- L31M ---

Non-structural protein 5A of HCV resistance associated polymorphisms in GT-1b samples, included L28M/V, R30H/Q, L31M, Q54H/N/Y, P58A/Q/S, Q62E/K/N/R/S, A92T/V and Y93F/H.. Inclusion Criteria: - Subjects chronically infected with HCV genotype 1 - Non-responder to prior therapy with peginterferon alfa and ribavirin - HCV RNA viral load of 100,00 IU/mL - Results of a liver biopsy ≤ 24 months prior to randomization consistent with chronic HCV infection; for compensated cirrhotics can be any time prior to randomization (compensated cirrhotics biopsy enrollment will be capped at 25% of randomized study population) - Ultrasound, CT scan or MRI results 12 months prior to randomization that do not demonstrate hepatocellular carcinoma - Body Mass Index (BMI) of 18 to 35 kg/m2 Exclusion Criteria: - Positive for Hepatitis B infection (HBsAg) or HIV-1/HIV-2 antibody at screening - Evidence of medical condition associated with chronic liver disease other than HCV - Evidence of decompensated cirrhosis based on radiologic criteria or biopsy Inclusion Criteria: - Subjects chronically infected with HCV genotype 1 - Non-responder to prior therapy with peginterferon alfa and ribavirin - HCV RNA viral load of 100,00 IU/mL - Results of a liver biopsy ≤ 24 months prior to randomization consistent with chronic HCV infection; for compensated cirrhotics can be any time prior to randomization (compensated cirrhotics biopsy enrollment will be capped at 25% of randomized study population) - Ultrasound, CT scan or MRI results 12 months prior to randomization that do not demonstrate hepatocellular carcinoma - Body Mass Index (BMI) of 18 to 35 kg/m2 Exclusion Criteria: - Positive for Hepatitis B infection (HBsAg) or HIV-1/HIV-2 antibody at screening - Evidence of medical condition associated with chronic liver disease other than HCV - Evidence of decompensated cirrhosis based on radiologic criteria or biopsy Hepatitis C Virus Hepatitis C Hepatitis null --- L28M --- --- R30H --- --- L31M ---