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) - Full Text View

Purpose

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.

Condition	Intervention	Phase
Hepatitis C, Chronic	Drug: RO5024048 Drug: danoprevir Drug: ritonavir Drug: ribavirin [Copegus] Drug: Copegus placebo Drug: peginterferon alfa-2a [Pegasys]	Phase 2

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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Interferon Ribavirin Ritonavir Peginterferon Alfa-2a

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Sustained virological response, defined as undetectable HVC RNA measured by Roche COBAS TaqMan HCV test [ Time Frame: 24 weeks after end of treatment ] [ Designated as safety issue: No ]
Safety: Incidence of adverse events [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Virological response (HCV RNA measured by Roche COBAS Taqman HCV test) [ Time Frame: up to 48 weeks ] [ Designated as safety issue: No ]
Impact of Copegus (ribavirin) on efficacy of the direct-acting antiviral combination regimen: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test) [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
Comparison of 12 and 24 weeks of treatment duration: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test) [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
Pharmacokinetics: Plasma concentrations of danoprevir, ritonavir, RO4995855 (parent drug of RO5024048) and ribavirin [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
Viral resistance: HCV RNA sequencing and phenotypic analyses [ Time Frame: up to 48 weeks ] [ Designated as safety issue: No ]
Effect of interleukin 28B genotype on efficacy: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test) [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
Quality of life: SF-36 questionnaire, Fatigue Severity Scale [ Time Frame: up to 36 weeks ] [ Designated as safety issue: No ]

Enrollment:	170
Study Start Date:	February 2011
Estimated Study Completion Date:	March 2013
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A	Drug: RO5024048 1000 mg bid orally, up to 24 weeks Drug: danoprevir 100 mg bid orally, up to 24 weeks Drug: ritonavir 100 mg bid orally, up to 24 weeks Drug: ribavirin [Copegus] 1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks
Experimental: B	Drug: RO5024048 1000 mg bid orally, up to 24 weeks Drug: danoprevir 100 mg bid orally, up to 24 weeks Drug: ritonavir 100 mg bid orally, up to 24 weeks Drug: Copegus placebo 1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks
Experimental: B extension All patients in treatment arm B were offered to receive Pegasys/Cogepus therapy for an additional 24 weeks.	Drug: ribavirin [Copegus] 1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks Drug: peginterferon alfa-2a [Pegasys] 180 mcg sc weekly, 24 weeks

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01278134

Show 32 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

No publications provided

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01278134 History of Changes
Other Study ID Numbers:	PP25213, 2010-022067-35
Study First Received:	January 14, 2011
Last Updated:	March 25, 2013
Health Authority:	France: Ministry of Health

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Interferons
Ribavirin

Ritonavir
Peginterferon alfa-2a
Interferon-alpha
Protease Inhibitors
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
HIV Protease Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on May 23, 2013