Back to resultsA 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)
Primary Purpose
Hepatitis C, Chronic
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Copegus placebo
RO5024048
danoprevir
peginterferon alfa-2a [Pegasys]
ribavirin [Copegus]
ritonavir
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C, Chronic
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Arm B Extension
RO5024048 & ritonavir-boosted danoprevir without Ribavirin (B)
RO5024048 and ritonavir-boosted danoprevir with Ribavirin (A)
Arm Description
All patients in treatment arm B were offered to receive Pegasys/Cogepus therapy for an additional 24 weeks.
Outcomes
Primary Outcome Measures
Sustained virological response, defined as undetectable HVC RNA measured by Roche COBAS TaqMan HCV test
Safety: Incidence of adverse events
Secondary Outcome Measures
Virological response (HCV RNA measured by Roche COBAS Taqman HCV test)
Impact of Copegus (ribavirin) on efficacy of the direct-acting antiviral combination regimen: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)
Comparison of 12 and 24 weeks of treatment duration: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)
Pharmacokinetics: Plasma concentrations of danoprevir, ritonavir, RO4995855 (parent drug of RO5024048) and ribavirin
Viral resistance: HCV RNA sequencing and phenotypic analyses
Effect of interleukin 28B genotype on efficacy: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)
Quality of life: SF-36 questionnaire, Fatigue Severity Scale
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01278134
Brief Title
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
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
October 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
170 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm B Extension
Arm Type
Experimental
Arm Description
All patients in treatment arm B were offered to receive Pegasys/Cogepus therapy for an additional 24 weeks.
Arm Title
RO5024048 & ritonavir-boosted danoprevir without Ribavirin (B)
Arm Type
Experimental
Arm Title
RO5024048 and ritonavir-boosted danoprevir with Ribavirin (A)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Copegus placebo
Intervention Description
1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks
Intervention Type
Drug
Intervention Name(s)
RO5024048
Intervention Description
1000 mg bid orally, up to 24 weeks
Intervention Type
Drug
Intervention Name(s)
danoprevir
Intervention Description
100 mg bid orally, up to 24 weeks
Intervention Type
Drug
Intervention Name(s)
peginterferon alfa-2a [Pegasys]
Intervention Description
180 mcg sc weekly, 24 weeks
Intervention Type
Drug
Intervention Name(s)
ribavirin [Copegus]
Intervention Description
1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks
Intervention Type
Drug
Intervention Name(s)
ritonavir
Intervention Description
100 mg bid orally, up to 24 weeks
Primary Outcome Measure Information:
Title
Sustained virological response, defined as undetectable HVC RNA measured by Roche COBAS TaqMan HCV test
Time Frame
24 weeks after end of treatment
Title
Safety: Incidence of adverse events
Time Frame
1.5 years
Secondary Outcome Measure Information:
Title
Virological response (HCV RNA measured by Roche COBAS Taqman HCV test)
Time Frame
up to 48 weeks
Title
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
Title
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
Title
Pharmacokinetics: Plasma concentrations of danoprevir, ritonavir, RO4995855 (parent drug of RO5024048) and ribavirin
Time Frame
up to 24 weeks
Title
Viral resistance: HCV RNA sequencing and phenotypic analyses
Time Frame
up to 48 weeks
Title
Effect of interleukin 28B genotype on efficacy: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)
Time Frame
1.5 years
Title
Quality of life: SF-36 questionnaire, Fatigue Severity Scale
Time Frame
up to 36 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
La Jolla
State/Province
California
ZIP/Postal Code
92037-1030
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96814
Country
United States
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96817
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
City
Lutherville
State/Province
Maryland
ZIP/Postal Code
21093
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07102
Country
United States
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37211
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23602
Country
United States
City
Vancouver
State/Province
Washington
ZIP/Postal Code
98664
Country
United States
City
Clichy
ZIP/Postal Code
92118
Country
France
City
Creteil
ZIP/Postal Code
94010
Country
France
City
Lille
ZIP/Postal Code
59037
Country
France
City
Marseille
ZIP/Postal Code
13285
Country
France
City
Montpellier
ZIP/Postal Code
34295
Country
France
City
Paris
ZIP/Postal Code
75651
Country
France
City
Berlin
ZIP/Postal Code
10969
Country
Germany
City
Berlin
ZIP/Postal Code
13353
Country
Germany
City
Frankfurt Am Main
ZIP/Postal Code
60590
Country
Germany
City
Hamburg
ZIP/Postal Code
20099
Country
Germany
City
Hannover
ZIP/Postal Code
30625
Country
Germany
City
Kiel
ZIP/Postal Code
24146
Country
Germany
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
City
Grafton
ZIP/Postal Code
1010
Country
New Zealand
12. IPD Sharing Statement
Citations:
PubMed Identifier
24637689
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.
Results Reference
derived
Learn more about this trial
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)
We'll reach out to this number within 24 hrs