Clinical trial NCT01278134: 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)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-01-17
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Sustained virological response, defined as undetectable HVC RNA measured by Roche COBAS TaqMan HCV test
timeFrame: 24 weeks after end of treatment
measure: Safety: Incidence of adverse events
timeFrame: 1.5 years
Secondary outcomes:
measure: Virological response (HCV RNA measured by Roche COBAS Taqman HCV test)
timeFrame: up to 48 weeks
measure: Impact of Copegus (ribavirin) on efficacy of the direct-acting antiviral combination regimen: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)
timeFrame: 1.5 years
measure: Comparison of 12 and 24 weeks of treatment duration: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)
timeFrame: 1.5 years
measure: Pharmacokinetics: Plasma concentrations of danoprevir, ritonavir, RO4995855 (parent drug of RO5024048) and ribavirin
timeFrame: up to 24 weeks
measure: Viral resistance: HCV RNA sequencing and phenotypic analyses
timeFrame: up to 48 weeks
measure: Effect of interleukin 28B genotype on efficacy: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)
timeFrame: 1.5 years
measure: Quality of life: SF-36 questionnaire, Fatigue Severity Scale
timeFrame: up to 36 weeks
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Orlando
country: United States
state: Florida
city: Marietta
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Honolulu
country: United States
state: Hawaii
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Lutherville
country: United States
state: Maryland
city: Detroit
country: United States
state: Michigan
city: Newark
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: New York
country: United States
state: New York
city: Providence
country: United States
state: Rhode Island
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Newport News
country: United States
state: Virginia
city: Vancouver
country: United States
state: Washington
city: Clichy
country: France
city: Creteil
country: France
city: Lille
country: France
city: Marseille
country: France
city: Montpellier
country: France
city: Paris
country: France
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Frankfurt Am Main
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Kiel
country: Germany
city: Leipzig
country: Germany
city: Grafton
country: New Zealand
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Tong X, Li L, Haines K, Najera I. Identification of the NS5B S282T resistant variant and two novel amino acid substitutions that affect replication capacity in hepatitis C virus-infected patients treated with mericitabine and danoprevir. Antimicrob Agents Chemother. 2014 Jun;58(6):3105-14. doi: 10.1128/AAC.02672-13. Epub 2014 Mar 17.