GS 5885 Administered Concomitantly With GS-9451, Tegobuvir and Ribavirin (RBV) in Chronic Genotype 1 Hepatitis C Virus (HCV) Infection

Study Overview
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Brief Summary
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The purpose of this phase 2 study is to determine whether 30 mg or 90 mg of GS-5885 when given with GS-9451, Tegobuvir and Ribavirin (RBV) for 12 or 24 weeks is effective, safe and tolerable in the treatment of Chronic Genotype 1 HCV Infection.

Official Title
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A Phase 2 Randomized, Open-Label Study of GS-5885 Administered Concomitantly With GS-9451, Tegobuvir and Ribavirin (RBV) to Treatment-Naive Subjects With Chronic Genotype 1 HCV Infection

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: GS-5885
* Drug: Tegobuvir
* Drug: GS-9451
* Drug: ribavirin tablet
* Drug: GS-5885


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects 18 to 70 years of age Chronic HCV infection for at least 6 months prior to Baseline (Day 1) Liver biopsy results (performed no more than 2 years prior to Screening) indicating the absence of cirrhosis Monoinfection with HCV genotype 1a or 1b HCV treatment-naïve Body mass index (BMI) between 18 and 36 kg/m2 Creatinine clearance ≥ 50 mL/min Subject agrees to use highly effective contraception methods if female of childbearing potential or sexually active male. Screening laboratory values within defined thresholds Exclusion Criteria: Autoimmune disease Decompensated liver disease or cirrhosis Poorly controlled diabetes mellitus Severe psychiatric illness Severe chronic obstructive pulmonary disease (COPD) Serological evidence of co-infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or another HCV genotype Suspicion of hepatocellular carcinoma or other malignancy (with exception of certain skin cancers) History of hemoglobinopathy Known retinal disease Subjects who are immunosuppressed Subjects with known, current use of amphetamines, cocaine, opiates (i.e., morphine, heroin), methadone, or ongoing alcohol abuse Subjects must have no history of clinically significant cardiac disease, including a family history of Long QT syndrome, and no relevant electrocardiogram (ECG) abnormalities at screening

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 |
| --- | --- |
| Active Comparator: Arm 1<br>GS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 24 weeks. | Drug: GS-5885<br>* tablet, 30 mg QD<br>Drug: Tegobuvir<br>* capsule, 30 mg BID<br>Drug: GS-9451<br>* tablet, 200 mg QD<br>Drug: ribavirin tablet<br>* (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)<br>|
| Active Comparator: Arm 2<br>GS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 12 or 24 weeks. | Drug: Tegobuvir<br>* capsule, 30 mg BID<br>Drug: GS-9451<br>* tablet, 200 mg QD<br>Drug: ribavirin tablet<br>* (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)<br>Drug: GS-5885<br>* tablet, 90 mg QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virologic response (SVR) |  | 24 weeks of off-treatment follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | To evaluate the safety and tolerability of 30 mg or 90 mg GS-5885 when given with GS-9451, Tegobuvir and RBV for 12 or 24 weeks. Safety endpoints will be analyzed by the number and percent of subjects with events or abnormalities for categorical values or 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment group. | through 24 weeks of off-treatment follow-up | 
| HCV RNA < Lower Limit Of Quantification | To evaluate the antiviral efficacy at Weeks 1, 2, 4, 12 and 24, as measured by the rates of HCV RNA < LLoQ and viral breakthrough and relapse. | Weeks 1, 2, 4, 12 and 24 | 
| Rescue Therapy Substudy SVR | To evaluate the antiviral efficacy (as defined by SVR) of the addition of pegylated interferon (PEG) for 24 weeks to GS-5885, GS-9451, tegobuvir and RBV in subjects who experience viral breakthrough on treatment. | 24 Weeks | 
| Emergence of viral resistance | To evaluate the emergence of viral resistance during treatment with GS-9451, Tegobuvir and RBV when given with 30 mg or 90 mg GS-5885 for 12 or 24 weeks. | 12 or 24 weeks | 
| Viral dynamics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV | HCV RNA levels, pharmacokinetics and viral sequencing | Through Week 2 of therapy | 
| Pharmacokinetics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV | Pharmacokinetics (Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½) will be listed and summarized for GS-5885, GS-9451 and Tegobuvir using descriptive statistics (e.g., sample size, arithmetic mean, geometric mean, % coefficient of variation, standard deviation, median, minimum, and maximum). Plasma concentrations of the study drug over time will be summarized using descriptive statistics | Through Week 2 of therapy | 

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