GS-5885, GS-9451 With Peginterferon Alfa 2a (PEG) and Ribavirin in Treatment-Naïve Subjects With Chronic Genotype 1 Hep C Virus Infection and IL28B CC Genotype

Study Overview
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Brief Summary
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This is a Phase 2, randomized, open-label exploratory study that will examine the antiviral efficacy, safety, and tolerability of Response guided treatment (RGT) with GS-5885 + GS-9451 + PEG/RBV (6 or 12 weeks), or Peginterferon Alfa 2a (PEG)/Ribavirin (RBV)alone (24 weeks) in treatment naïve subjects with chronic Hep C (HCV) infection with genotype (GT) 1 and IL28B CC genotype.

Official Title
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A Phase 2 Randomized, Open-Label, Exploratory Trial of GS-5885, GS-9451 With Peginterferon Alfa 2a and Ribavirin (RBV) in Treatment-Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection and IL28B CC Genotype

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: GS-5885
* Drug: GS-9451
* Drug: RBV
* Drug: PEG


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 (≤ 3 years prior to screening) indicating the absence of cirrhosis. Alternatively a non-invasive alternative to liver biopsy (such as FibroTest, FibroScan, or Acoustic Radiation Force Impulse imaging) within 6 months of Screening in countries where allowed Monoinfection with HCV genotype 1a or 1b HCV RNA > 10^4 IU/mL at Screening IL28B CC genotype HCV treatment naïve Candidate for PEG/RBV therapy Body mass index (BMI) between 18 and 36 kg/m2 Creatinine clearance >= 50 mL/min Agree to use two forms of highly effective contraception methods for the duration of the study and for 7 months after the last dose study medication. Females of childbearing potential must have negative pregnancy test at Screening and Baseline Exclusion Criteria: Exceed defined thresholds for key laboratory parameters at Screening 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 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. Subjects on stable methadone maintenance treatment for at least 6 months prior to Screening may be included into the study Use of prohibited concomitant medications two weeks prior to baseline through the end of treatment

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Response-Guided Therapy with GS-5885 30 mg plus GS-9451 200 mg, plus PEG and RBV for 6 or 12 weeks. | Drug: GS-5885<br>* GS-5885 30 mg tablet administered orally once daily<br>Drug: GS-9451<br>* GS-9451 200 mg tablet administered orally once daily<br>Drug: RBV<br>* Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>Drug: PEG<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection<br>|
| Experimental: Arm 2<br>Response-Guided Therapy with PEG and RBV for 24 weeks. | Drug: RBV<br>* Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)<br>Drug: PEG<br>* Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virologic response (SVR) | Sustained virologic response (SVR, defined as plasma HCV RNA < lower limit of quantification [LLoQ] at 24 weeks after treatment cessation) following treatment with GS-5885 + GS-9451 + PEG/RBV for 6 or 12 weeks, or PEG/RBV for 24 weeks in IL28B CC subjects. | 30 , 36 or 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of therapy | Safety and tolerability of the therapy is measured by frequency of laboratory abnormalities , reported adverse events and discontinuations due to adverse events. | Up to 48 weeks | 
| Virologic response | Virologic response at Weeks 2, 4, 6, 8, 10, and 12 (depending on treatment arm) as measured by the rates of HCV RNA < LLoQ and viral breakthrough and relapse | Weeks 2, 4, 6, 8, 10, and 12 | 
| Compare SVR | Compare SVR following treatment with GS-5885 + GS-9451 + PEG/RBV for 6 weeks versus 12 weeks. | Weeks 30 and 36 | 
| Viral resistance | Characterize viral resistance to GS-5885 and GS-9451 when administered in combination with PEG/RBV | Up to 96 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis C, IL28B CC Genotype, Treatment naive, Peginterferon α-2a (PEG), Genotype 1a/b, GS 9451, GS 5885, Ribavirin (RBV), HCV NS5A inhibitor, HCV NS3 protease inhibitor