A Study of Combination Treatment With an HCV Polymerase Inhibitor (RO5024048) and an HCV Protease Inhibitor (RO5190591/Danoprevir) in Genotype 1 Chronic Hepatitis C Patients

Study Overview
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Brief Summary
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This 7 cohort study will evaluate the efficacy and safety of combination treatment with an HCV nucleoside polymerase inhibitor(RO5024048)and an HCV protease inhibitor(RO5190591/ITMN-191/danoprevir) in patients with chronic hepatitis C, genotype 1.Cohorts A,B,C,D and G will be treatment-naive patients, cohort E will be treatment-experienced excluding null responders, and cohort F will be null responders. Cohorts A and B will evaluate doses of 500mg po bid RO5024048 and 100mg po q8h RO5190591, alone or in combination, for up to 7 or 14 days. Cohort C will evaluate combination treatment with either 1000mg po bid RO5024048 and 100mg q8h RO5190591 or 500mg po bid RO5024048 and 200mg q8h RO5190591 for 14 days. Cohort D will evaluate 1000mg po bid RO5024048 and 200mg q8h RO5190591 for 14 days.Cohort E will evaluate 1000mg RO5024048/600mg RO5190591 po twice daily for 14 days, and Cohorts F and G will evaluate 1000mg RO5024048/900mg RO5190591 po twice daily for 14 days. Cohorts will be tested sequentially or in parallel, if supported by appropriate safety and pharmacokinetic data.Following the last dose of study medication patients have the option of continuing treatment with Standard of care therapies. The anticipated time on study treatment is <3 months, and the target sample size is <100 individuals.

Official Title
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A Randomized, Placebo-controlled, Dose-ranging Study to Evaluate the Safety, Tolerability and Antiviral Activity of Combination Treatment With an HCV Polymerase Inhibitor (RO5024048) and an HCV Protease Inhibitor (RO5190591) in Genotype 1 Chronic Hepatitis C Patients. INFORM 1

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: RO5024048
* Drug: danoprevir
* Drug: danoprevir
* Drug: danoprevir
* Drug: danoprevir
* Drug: danoprevir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, 18-65 years of age; chronic hepatitis C, genotype 1. Exclusion Criteria: decompensated liver disease, or impaired liver function; presence or history of non-hepatitis C chronic liver disease; HBsAg or HIV infection; history of cancer within 5 years, other than localized or in situ cancer of the skin.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br> | Drug: RO5024048<br>* 500mg po bid/100mg po q8h for 7 days<br>|
| Experimental: Cohort B<br> | Drug: danoprevir<br>* 500mg po bid/100mg po q8h for 14 days<br>|
| Experimental: Cohort C<br> | Drug: danoprevir<br>* 1000mg po bid/100mg po q8h for 14 days\n500mg po bid/200mg po q8h for 14 days<br>|
| Experimental: Cohort D<br> | Drug: danoprevir<br>* 1000mg po bid/200mg po q8h for 14 days<br>|
| Experimental: Cohort E<br> | Drug: danoprevir<br>* 1000mg/600mg po twice daily for 14 days<br>|
| Experimental: Cohort F<br> | Drug: danoprevir<br>* 1000mg/900mg po twice daily for 14 days<br>|
| Experimental: Cohort G<br> | Drug: danoprevir<br>* 1000mg/900mg po twice daily for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCV RNA |  | At each clinic visit, throughout study | 
| Adverse events, laboratory parameters, vital signs |  | At each clinic visit, throughout study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters;viral resistance |  | At intervals, throughout study |