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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

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

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

Type: Drug

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

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

Type: Drug

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:
Hepatitis
Genes 90
CD247 CTNNB1 ATP7B CASP10 PIEZO1 GUSB BLNK SHPK CYP7A1 IL17RA IGF2R CASP8 SH2D1A SLC25A15 BTK BTK C4B CD79B VPS33B XIAP SERPINA1 PIK3R1 GLIS3 POU2AF1 CIITA FOXP3 TPP2 RFX5 CIITA RASGRP1 RFXANK SLC25A15 AXIN1 TCF4 CD3D TP53 IL12A PRKCD CD40LG BTK IGHM IL17RC ALMS1 TRAF3IP2 KRT8 FAS LRRC8A FAS IL17F XIAP SPIB C1S RFX5 RFXAP MST1 TTC7A COG8 SKIV2L VIPAS39 IGLL1 PDGFRL TNFSF15 HSD3B7 CD3E AMACR ATP7B FASLG RFXANK IL12RB1 TCF3 CD79A KRT18 IRF5 MET PIK3CA MMEL1 ITCH TBX19 IL21R AIRE RFXAP TTC7A CLEC7A GPR35 ATP7A CYP7B1 STAT1 PGM1 APC TNPO3