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)

Hepatitis C, Chronic Clinical Trial

Official title:

INFORM-SVR: A Randomized, Multi-Center Study of Interferon-Free Treatment With a Combination of a Polymerase Inhibitor (RO5024048) and a Ritonavir Boosted HCV Protease Inhibitor (RO5190591/r, DNV/r) With or Without Copegus® in Interferon Naïve HCV Genotype 1 Infected Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01278134
• Other study ID #: PP25213
• Secondary ID: 2010-022067-35
• Status: Completed
• Phase: Phase 2
• First received: January 14, 2011
• Last updated: November 1, 2016
• Start date: February 2011
• Est. completion date: October 2012

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 170
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• Copegus placebo
1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks
• RO5024048
1000 mg bid orally, up to 24 weeks
• danoprevir
100 mg bid orally, up to 24 weeks
• peginterferon alfa-2a [Pegasys]
180 mcg sc weekly, 24 weeks
• ribavirin [Copegus]
1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks
• ritonavir
100 mg bid orally, up to 24 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  France,  Germany,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virological response, defined as undetectable HVC RNA measured by Roche COBAS TaqMan HCV test		24 weeks after end of treatment	No
Primary	Safety: Incidence of adverse events		1.5 years	No
Secondary	Virological response (HCV RNA measured by Roche COBAS Taqman HCV test)		up to 48 weeks	No
Secondary	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	No
Secondary	Comparison of 12 and 24 weeks of treatment duration: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)		1.5 years	No
Secondary	Pharmacokinetics: Plasma concentrations of danoprevir, ritonavir, RO4995855 (parent drug of RO5024048) and ribavirin		up to 24 weeks	No
Secondary	Viral resistance: HCV RNA sequencing and phenotypic analyses		up to 48 weeks	No
Secondary	Effect of interleukin 28B genotype on efficacy: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)		1.5 years	No
Secondary	Quality of life: SF-36 questionnaire, Fatigue Severity Scale		up to 36 weeks	No