SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01949168

Developed by Shray Alag, 2019.
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 Hepatitis C Hepatitis, Chronic Hepatitis C, Chronic
HPO: Chronic active hepatitis Chronic hepatitis Hepatitis

3 Interventions

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

Type: Drug

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

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

Type: Drug

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

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

Type: Drug

Boceprevir triple therapy with 5-day lead in Boceprevir triple therapy 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:
Chronic active hepatitis
Genes 5
KRT8 ALMS1 C4B KRT18 AIRE
Chronic hepatitis
Genes 11
KRT8 ALMS1 RFXANK C4B KRT18 CIITA AIRE IL21R RFX5 RFXAP CD40LG
Hepatitis
Genes 74
TTC7A MST1 TRAF3IP2 TPP2 TBX19 IL12A MET IL12RB1 RASGRP1 TCF4 HSD3B7 KRT8 SERPINA1 TCF3 VIPAS39 ATP7A IGF2R MMEL1 ATP7B ALMS1 SPIB KRT18 VPS33B CIITA PDGFRL PIK3CA GPR35 CYP7A1 GUSB PIK3R1 AMACR RFXANK SHPK IGHM PIEZO1 SLC25A15 BTK IL21R CD40LG BLNK GLIS3 APC CLEC7A AIRE LRRC8A CASP8 POU2AF1 XIAP CASP10 C1S CYP7B1 PRKCD CD79A CD79B IRF5 C4B IL17RC IL17RA IGLL1 CTNNB1 FAS SKIV2L FASLG SH2D1A RFX5 IL17F RFXAP TNFSF15 TNPO3 PGM1 STAT1 TP53 AXIN1 FOXP3