GS-5885 Alone or in Combination With GS-9451 With Peginterferon Alfa 2a and Ribavirin in Treatment Chronic Genotype 1 Hepatitis C Virus

Study Overview
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Brief Summary
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This is a Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy with GS-5885 Alone or in Combination with GS-9451 with Peginterferon Alfa 2a and Ribavirin in Treatment Naïve Subjects with Chronic Genotype 1 Hepatitis C Virus Infection.

Official Title
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A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy With GS-5885 Alone or in Combination With GS-9451 With Peginterferon Alfa 2a and Ribavirin in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: GS-5885
* Drug: GS-9451
* Biological: peginterferon alfa-2a
* Drug: ribavirin tablet
* Drug: GS-9451 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females 18-70 years of age Chronic HCV infection Subjects must have liver biopsy results (≤ 2 years prior to Screening) indicating the absence of cirrhosis. Monoinfection with HCV genotype 1 HCV RNA > 10^4 IU/mL at Screening HCV treatment naïve Candidate for PEG/RBV therapy Body mass index (BMI) 18-36 kg/m2, inclusive Agree to use two forms of highly effective contraception methods for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have negative pregnancy test at Screening and Baseline. Exclusion Criteria: Pregnant female or male with pregnant female partner Exceed defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, thyroid stimulating hormone (TSH) Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed. Subjects with current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Patients on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to Screening may be included into the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Active Comparator: Arm 1<br>RGT with GS-5885 30 mg QD + GS-9451 200 mg QD + PEG/RBV | Drug: GS-5885<br>* tablet, 30 mg QD<br>Drug: GS-9451<br>* tablet, 200 mg QD<br>Biological: peginterferon alfa-2a<br>* (solution for injection) 180 µg/week<br>Drug: ribavirin tablet<br>* ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)<br>|
| Placebo Comparator: Arm 2<br>RGT with GS-5885 30 mg QD + GS-9451 placebo QD + PEG/RBV | Drug: GS-5885<br>* tablet, 30 mg QD<br>Biological: peginterferon alfa-2a<br>* (solution for injection) 180 µg/week<br>Drug: ribavirin tablet<br>* ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)<br>Drug: GS-9451 Placebo<br>* Placebo to match GS-9451 QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the antiviral efficacy of response guided therapy. | To evaluate the antiviral efficacy as measured by sustained virologic response (SVR, defined as plasma HCV RNA < Lower Limit of Quantification (LLoQ) at 24 weeks post-treatment) of response guided therapy (RGT) with GS-5885 + GS-9451 + PEG/RBV, or GS-5885 + PEG/RBV. | Through 24 weeks post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of each regimen. | The primary safety endpoint is any AE leading to permanent discontinuation of study drugs. | Through 24 weeks post-treatment | 
| To characterize viral dynamics of GS-5885 and GS-9451 when administered with PEG and RBV. | HCV RNA levels, pharmacokinetics and viral sequencing | Through Day 10 on study | 
| To characterize the viral resistance to GS-5885 and GS-9451 when administered in combination with PEG and RBV. | Plasma samples will be collected and stored at each visit for possible resistance analysis. | 12 or 24 weeks | 
| To characterize steady state pharmacokinetics of GS-5885 and GS-9451 when administered with PEG and RBV. | Plasma concentrations of the study drug over time will be summarized using descriptive statistics. | Through 48 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C, HCV, Rapid Virologic Response, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy HCV RNA, Protease inhibitor, Treatment naïve, GS-5885, GS-9451