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Report for Clinical Trial NCT01949168

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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 Chronic Hepatitis C
MeSH:Hepatitis C Hepatitis C, Chronic Hepatitis
HPO:Hepatitis

3 Interventions

Name: Victrelis® (boceprevir) 800mg by mouth, TID (200 mg tablets)

Type: Drug
Group Labels: 2

Boceprevir triple therapy Boceprevir triple therapy with 5-day lead in

Name: Peg-Intron® (peginterferon-α-2b), 1.5ug/kg sc injection

Type: Drug
Group Labels: 3

Boceprevir triple therapy Boceprevir triple therapy with 5-day lead in Standard of Care

Name: Rebetol® (ribavirin), 1000/1200mg by mouth daily

Type: Drug
Group Labels: 3

Boceprevir triple therapy Boceprevir triple therapy with 5-day lead in Standard of Care

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
Purpose: Treatment

Allocation: Randomized

Parallel Assignment

There is one SNP

SNPs

1 rs12979860

- 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).


HPO Nodes

HPO:
HP:0012115: Hepatitis
Genes 91
TNPO3 AIRE CD247 PIK3R1 ATP7A TRAF3IP2 APC COG6 PGM1 C4B PIEZO1 AXIN1 COG8 POU2AF1 CD79A IL17RC TNFSF15 CD40LG TCF4 ITCH SKIV2L CYP7A1 IL17F BLNK TPP2 RFXAP TCF3 VPS33B SLC25A15 C1S CLEC7A FAS HSD3B7 KRT18 GUSB FASLG ALMS1 CYP7B1 CIITA TBX19 XIAP TP53 BTK LRRC8A RASGRP1 CASP10 CD3E PIK3CA XIAP VIPAS39 FOXP3 TTC7A TTC7A STAT1 IL12RB1 RFXANK IRF5 SH2D1A IL21R MST1 RFXANK CD3D CASP8 AMACR MMEL1 IL12A CD79B IGHM GLIS3 SHPK CIITA FAS MET IL17RA RFXAP IGLL1 SPIB KRT8 ATP7B BTK IGF2R PDGFRL RFX5 RFX5 ATP7B BTK GPR35 SERPINA1 PRKCD CTNNB1 SLC25A15
Protein Mutations 29
A181V A92T C282Y E62D G1764A H54Y H58C H63D L28M L31M L528M M204I M204V M28L M552I M552V N236T N370S P1028S P58A Q215S Q30H Q54H Q62E Q80K R30H Y93C Y93F Y93H
SNP 20
rs10813831 rs1127354 rs11795404 rs12356193 rs12979860 rs12992677 rs17037122 rs179008 rs2066842 rs2067085 rs2464266 rs3853839 rs41308230 rs4588 rs5743844 rs6592052 rs7041 rs7270101 rs7549785 rs8099917