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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01278134




Registration number
NCT01278134
Ethics application status
Date submitted
14/01/2011
Date registered
17/01/2011
Date last updated
2/11/2016

Titles & IDs
Public 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)
Scientific 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
Secondary ID [1] 0 0
2010-022067-35
Secondary ID [2] 0 0
PP25213
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Copegus placebo
Treatment: Drugs - RO5024048
Treatment: Drugs - danoprevir
Treatment: Drugs - peginterferon alfa-2a [Pegasys]
Treatment: Drugs - ribavirin [Copegus]
Treatment: Drugs - ritonavir

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

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

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


Treatment: Drugs: Copegus placebo
1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks

Treatment: Drugs: RO5024048
1000 mg bid orally, up to 24 weeks

Treatment: Drugs: danoprevir
100 mg bid orally, up to 24 weeks

Treatment: Drugs: peginterferon alfa-2a [Pegasys]
180 mcg sc weekly, 24 weeks

Treatment: Drugs: ribavirin [Copegus]
1000 mg or 1200 mg daily orally in split doses (morning/evening), up to 24 weeks

Treatment: Drugs: ritonavir
100 mg bid orally, up to 24 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Sustained virological response, defined as undetectable HVC RNA measured by Roche COBAS TaqMan HCV test
Timepoint [1] 0 0
24 weeks after end of treatment
Primary outcome [2] 0 0
Safety: Incidence of adverse events
Timepoint [2] 0 0
1.5 years
Secondary outcome [1] 0 0
Virological response (HCV RNA measured by Roche COBAS Taqman HCV test)
Timepoint [1] 0 0
up to 48 weeks
Secondary outcome [2] 0 0
Impact of Copegus (ribavirin) on efficacy of the direct-acting antiviral combination regimen: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)
Timepoint [2] 0 0
1.5 years
Secondary outcome [3] 0 0
Comparison of 12 and 24 weeks of treatment duration: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)
Timepoint [3] 0 0
1.5 years
Secondary outcome [4] 0 0
Pharmacokinetics: Plasma concentrations of danoprevir, ritonavir, RO4995855 (parent drug of RO5024048) and ribavirin
Timepoint [4] 0 0
up to 24 weeks
Secondary outcome [5] 0 0
Viral resistance: HCV RNA sequencing and phenotypic analyses
Timepoint [5] 0 0
up to 48 weeks
Secondary outcome [6] 0 0
Effect of interleukin 28B genotype on efficacy: viral response (HCV RNA measured by Roche COBAS TaqMan HCV test)
Timepoint [6] 0 0
1.5 years
Secondary outcome [7] 0 0
Quality of life: SF-36 questionnaire, Fatigue Severity Scale
Timepoint [7] 0 0
up to 36 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2012
Sample size
Target
Accrual to date
Final
170
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Hawaii
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New Mexico
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Rhode Island
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
France
State/province [17] 0 0
Clichy
Country [18] 0 0
France
State/province [18] 0 0
Creteil
Country [19] 0 0
France
State/province [19] 0 0
Lille
Country [20] 0 0
France
State/province [20] 0 0
Marseille
Country [21] 0 0
France
State/province [21] 0 0
Montpellier
Country [22] 0 0
France
State/province [22] 0 0
Paris
Country [23] 0 0
Germany
State/province [23] 0 0
Berlin
Country [24] 0 0
Germany
State/province [24] 0 0
Frankfurt Am Main
Country [25] 0 0
Germany
State/province [25] 0 0
Hamburg
Country [26] 0 0
Germany
State/province [26] 0 0
Hannover
Country [27] 0 0
Germany
State/province [27] 0 0
Kiel
Country [28] 0 0
Germany
State/province [28] 0 0
Leipzig
Country [29] 0 0
New Zealand
State/province [29] 0 0
Grafton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01278134
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01278134