A Multiple Ascending Dose Study of GS 5885 in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and activity of escalating, multiple, oral doses of GS-5885 in subjects with chronic genotype 1 Hepatitis C Virus (HCV) infection. Each participant in the study will be sequestered in the clinic for the initial 5 days of the study.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Escalating, Multiple, Oral Doses of GS 5885 in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection

Conditions
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HCV Infection

Intervention / Treatment
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* Drug: GS-5885
* Drug: Placebo
* Drug: GS-5885
* Drug: Placebo
* Drug: GS-5885
* Drug: Placebo
* Drug: GS-5885
* Drug: Placebo
* Drug: GS-5885
* Drug: Placebo
* Drug: GS-5885
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronically infected with HCV genotype 1 HCV treatment-naïve Not co-infected with HIV or HBV HCV RNA viral load of at least 100,000 IU/mL BMI 19 to 35 kg/m2 Subject agrees to use highly effective contraception methods if female of childbearing potential or sexually active male. Exclusion Criteria: History of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol Decompensated liver disease or cirrhosis or evidence of hepatocellular carcinoma Serological evidence of co-infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or another HCV genotype Subjects with known, current use of amphetamines and/or cocaine; subjects taking methadone or buprenorphine (opioid replacement therapy) or ongoing alcohol abuse

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 |
| --- | --- |
| Active Comparator: Cohort 1<br>GS-5885 (3 mg), once daily or matching placebo, once daily | Drug: GS-5885<br>* tablet, oral, 3 mg once daily for 3 days<br>Drug: Placebo<br>* tablet, oral, once daily for 3 days<br>|
| Active Comparator: Cohort 2<br>GS-5885 (10 mg), once daily or matching placebo, once daily | Drug: GS-5885<br>* tablet, oral, 10 mg once daily for 3 days<br>Drug: Placebo<br>* tablet, oral, once daily for 3 days<br>|
| Active Comparator: Cohort 3<br>GS-5885 (30 mg), once daily or matching placebo, once daily | Drug: GS-5885<br>* tablet, oral, 30 mg once daily for 3 days<br>Drug: Placebo<br>* tablet, oral, once daily for 3 days<br>|
| Active Comparator: Cohort 4<br>GS-5885 ( up to 90 mg), once daily or matching placebo, once daily | Drug: GS-5885<br>* tablet, oral, up to 90 mg once daily for 3 days<br>Drug: Placebo<br>* tablet, oral, once daily for 3 days<br>|
| Active Comparator: Cohort 5<br>GS-5885 (up to 90 mg), once daily or matching placebo, once daily | Drug: GS-5885<br>* tablet, oral, up to 90 mg once daily for 3 days<br>Drug: Placebo<br>* tablet, oral, once daily for 3 days<br>|
| Active Comparator: Cohort 6 (optional)<br>GS-5885 (up to 90 mg), once daily or matching placebo, once daily | Drug: GS-5885<br>* tablet, oral, up to 90 mg once daily for 3 days<br>Drug: Placebo<br>* tablet, oral, once daily for 3 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects reporting an adverse event or experiencing a laboratory abnormality |  | Safety and tolerability assessments will be performed up to Study Day 14 following administration of multiple doses of GS-5885 or placebo for 3 days | 
| Antiviral activity measures: measured by change in plasma HCV RNA levels form baseline |  | Assessed up to Study Day 14 following administration of multiple doses of GS-5885 or placebo for 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of GS-5885 plasma concentration over time |  | Assessed up to Study Day 14 following administration of multiple doses of GS-5885 or placebo for 3 days | 
| Emergence of viral resistance |  | Up to 48 weeks following Study Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C, HCV RNA, multiple ascending dose, NS5A, GS-5885, chronic genotype 1 HCV infection