A Study of RO5024048 in Combination With Ritonavir-Boosted Danoprevir With or Without Copegus (Ribavirin) in Interferon-Naïve Patients With Chronic Hepatitis C Genotype 1 (INFORM-SVR)

Phase 2

Completed

• Conditions: Hepatitis C, Chronic
• Interventions: Drug: peginterferon alfa-2a [Pegasys]; Drug: Copegus placebo; Drug: ribavirin [Copegus]; Drug: RO5024048; Drug: danoprevir; Drug: ritonavir

• Registration Number: NCT01278134
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This multicenter, randomized, double-blind, parallel group study will evaluate the safety and efficacy of the combination RO5024048 and ritonavir-boosted danoprevir with and without Copegus (ribavirin) in patients with chronic hepatitis C genotype 1. In arm A and B, interferon treatment-naïve patients will receive 1000 mg RO5024048 orally twice daily and 100 mg danoprevir with 100 mg ritonavir orally twice daily plus either Copegus (1000 mg or 1200 mg orally daily) or placebo for 12 weeks. Depending on viral response and treatment arm patients will be re-randomized to continue assigned treatment for additional 12 weeks or stop all treatment. The anticipated time on study treatment is up to 24 weeks plus a 24-week follow-up.

As of 29. September 2011, Arm B patients (placebo-containing arm) will be offered, in conjunction with the current treatment, Pegasys (peginterferon alfa-2a) 180 mcg subcutaneously weekly plus Copegus 1000mg or 1200 mg orally daily for 24 weeks, with a 24-week follow-up.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-01-14
• Study First Submitted QC: 2011-01-14
• Study First Posted: 2011-01-17
• Study Start: 2011-02
• Primary Completion: 2012-10
• Study Completion: 2012-10
• Disposition First Submitted: 2016-07-20
• Disposition First Submitted QC: 2016-07-20
• Disposition First Posted: 2016-07-22
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

• Adult patient, >/= 18 years of age
• Chronic Hepatitis C of >/= 6 months duration at screening
• HCV genotype 1 and quantifiable HCV RNA at screening (Roche COBAS TaqMan HCV test)
• Naïve for treatment with interferon (pegylated or non-pegylated)
• Body Mass Index (BMI) 18-35 inclusive, minimum weight 45 kg
• Females of child-bearing potential and males with female partners of childbearing potential must use 2 forms of effective non-hormonal contraception

Exclusion Criteria

• Pregnant or lactating women and males with female partners who are pregnant or lactating
• Decompensated liver disease or impaired liver function
• Cirrhosis or incomplete/transition to cirrhosis
• Non-hepatitis C chronic liver disease
• Hepatitis B or HIV infection
• History of neoplastic disease within the last 5 years, except for localized or in situ carcinoma of the skin
• History of pre-existing renal disease (except for nephrolithiasis) or severe cardiac disease
• History of drug or alcohol abuse within the last year or alcohol consumption of > 2 units per day; cannabinoid use is excepted

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B Extension	ribavirin [Copegus]	All patients in treatment arm B were offered to receive Pegasys/Cogepus therapy for an additional 24 weeks.
RO5024048 & ritonavir-boosted danoprevir without Ribavirin (B)	ritonavir	-
RO5024048 & ritonavir-boosted danoprevir without Ribavirin (B)	RO5024048	-
RO5024048 and ritonavir-boosted danoprevir with Ribavirin (A)	ribavirin [Copegus]	-
RO5024048 & ritonavir-boosted danoprevir without Ribavirin (B)	danoprevir	-
RO5024048 and ritonavir-boosted danoprevir with Ribavirin (A)	RO5024048	-
RO5024048 and ritonavir-boosted danoprevir with Ribavirin (A)	danoprevir	-
Arm B Extension	peginterferon alfa-2a [Pegasys]	All patients in treatment arm B were offered to receive Pegasys/Cogepus therapy for an additional 24 weeks.
RO5024048 & ritonavir-boosted danoprevir without Ribavirin (B)	Copegus placebo	-
RO5024048 and ritonavir-boosted danoprevir with Ribavirin (A)	ritonavir	-

Primary Outcome Measures

Name	Time	Method
Safety: Incidence of adverse events	1.5 years
Sustained virological response, defined as undetectable HVC RNA measured by Roche COBAS TaqMan HCV test	24 weeks after end of treatment

Secondary Outcome Measures

Name	Time	Method
Virological response (HCV RNA measured by Roche COBAS Taqman HCV test)	up to 48 weeks
Impact of Copegus (ribavirin) on efficacy of the direct-acting antiviral combination regimen: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)	1.5 years
Comparison of 12 and 24 weeks of treatment duration: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)	1.5 years
Pharmacokinetics: Plasma concentrations of danoprevir, ritonavir, RO4995855 (parent drug of RO5024048) and ribavirin	up to 24 weeks
Viral resistance: HCV RNA sequencing and phenotypic analyses	up to 48 weeks
Effect of interleukin 28B genotype on efficacy: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)	1.5 years
Quality of life: SF-36 questionnaire, Fatigue Severity Scale	up to 36 weeks