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)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01278134

Collaborator

(none)

170

Enrollment

Locations

Arms

Duration (Months)

5.3

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

170 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, 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

Study Start Date :

Feb 1, 2011

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm B Extension All patients in treatment arm B were offered to receive Pegasys/Cogepus therapy for an additional 24 weeks.	Drug: peginterferon alfa-2a [Pegasys] 180 mcg sc weekly, 24 weeks Drug: ribavirin [Copegus] 1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks
Experimental: RO5024048 & ritonavir-boosted danoprevir without Ribavirin (B)	Drug: Copegus placebo 1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks 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
Experimental: RO5024048 and ritonavir-boosted danoprevir with Ribavirin (A)	Drug: RO5024048 1000 mg bid orally, up to 24 weeks Drug: danoprevir 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 Drug: ritonavir 100 mg bid orally, up to 24 weeks

Arm

Intervention/Treatment

Experimental: Arm B Extension

All patients in treatment arm B were offered to receive Pegasys/Cogepus therapy for an additional 24 weeks.

Drug: peginterferon alfa-2a [Pegasys]

180 mcg sc weekly, 24 weeks

Drug: ribavirin [Copegus]

1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks

Experimental: RO5024048 & ritonavir-boosted danoprevir without Ribavirin (B)

Drug: Copegus placebo

1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks

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

Experimental: RO5024048 and ritonavir-boosted danoprevir with Ribavirin (A)

Drug: RO5024048

1000 mg bid orally, up to 24 weeks

Drug: danoprevir

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

Drug: ritonavir

100 mg bid orally, up to 24 weeks

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	City	State	Country	Postal Code
1	La Jolla	California	United States	92037-1030
2	Sacramento	California	United States	95817
3	Orlando	Florida	United States	32809
4	Marietta	Georgia	United States	30060
5	Honolulu	Hawaii	United States	96814
6	Honolulu	Hawaii	United States	96817
7	Chicago	Illinois	United States	60637
8	Indianapolis	Indiana	United States	46202
9	Lutherville	Maryland	United States	21093
10	Detroit	Michigan	United States	48202
11	Newark	New Jersey	United States	07102
12	Albuquerque	New Mexico	United States	87131
13	New York	New York	United States	10021
14	Providence	Rhode Island	United States	02905
15	Nashville	Tennessee	United States	37211
16	Houston	Texas	United States	77030
17	Newport News	Virginia	United States	23602
18	Vancouver	Washington	United States	98664
19	Clichy		France	92118
20	Creteil		France	94010
21	Lille		France	59037
22	Marseille		France	13285
23	Montpellier		France	34295
24	Paris		France	75651
25	Berlin		Germany	10969
26	Berlin		Germany	13353
27	Frankfurt Am Main		Germany	60590
28	Hamburg		Germany	20099
29	Hannover		Germany	30625
30	Kiel		Germany	24146
31	Leipzig		Germany	04103
32	Grafton		New Zealand	1010