A Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-6620 in Treatment Naïve Subjects With Chronic Hepatitis C Virus Infection

Study Overview
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Brief Summary
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A Double-Blind, Randomized, Placebo-Controlled, Multiple Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-6620 in Treatment Naïve Subjects with Chronic Hepatitis C Virus Infection.

Official Title
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A Phase 1 Double-Blind, Randomized, Placebo-Controlled, Multiple Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-6620 in Treatment Naïve Subjects With Chronic Hepatitis C Virus Infection

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: GS-6620
* Drug: GS-6620
* Drug: GS-6620
* Drug: GS-6620
* Drug: GS-6620
* Drug: GS-6620
* Drug: GS-6620 tablet, 450 mg BID
* Drug: GS-6620 tablet
* Drug: GS-6620 tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects (18-60 years of age or up to 64 years of age with approval) Documented chronic HCV infection to be of at least 6 months duration and plasma HCV RNA ≥ 5 log10 IU/mL at screening. HCV treatment naïve Estimated creatinine clearance ≥ 80 mL/min, QTcF interval ≤ 450 msec, QRS duration < 100 msec, PR interval < 220 msec, Body mass index (BMI) of 19.0 to 34.0 kg/m2, inclusive. Eligible subjects must also be HCV treatment-naïve. Exclusion Criteria: Subjects with prior documentation of cirrhosis, excessive current alcohol intake, any evidence of hepatocellular carcinoma (i.e., α-fetoprotein > 50 ng/mL or by any other standard of care measure) Urine drug screen positive for illicit/illegal drugs ALT and AST levels > 5 times the upper limit of the normal range (ULN) Direct bilirubin > ULN, clinical or other laboratory evidence of hepatic decompensation (i.e., platelets < 100,000/mm3, prothrombin time ≥ 1.5 × ULN and albumin < 3.5 g/dL) are not eligible for study participation. Subjects with an absolute neutrophil count (ANC) < 1,000 cells/mm3 (< 750 cells/mm3 for black or African-American subjects), hemoglobin (Hb) < 11 g/dL, Coinfected with hepatitis B virus (HBV), human immunodeficiency virus (HIV), or another HCV genotype (other than type 1 for Cohorts 1-5 and type 2 or 3 for Cohort 6) are not eligible for study participation. Evidence of hepatocellular carcinoma Any sign of decompensated liver disease, including prothrombin time ≥ 1.5 X ULN, platelets < 100,000/mm3 or albumin < 3.5 g/dL at screening OR current or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy or variceal hemorrhage) History of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol History of a primary gastrointestinal disorder that could interfere with the absorption of the study drug or that could interfere with normal gastrointestinal anatomy or motility

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort 1<br>(N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 50 mg GS-6620 or placebo QD in the morning with food [total daily dose (TDD) = 50 mg] for 5 days | Drug: GS-6620<br>* GS-6620 tablet, 50 mg QD<br>|
| Other: Cohort 2<br>(N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 100 mg GS-6620 or placebo QD in the morning with food (TDD = 100 mg) for 5 days | Drug: GS-6620<br>* GS-6620 tablet, 100 mg QD<br>|
| Other: Cohort 3<br>Cohort 3 (N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 300 mg GS 6620 or placebo QD in the morning with food (TDD = 300 mg) for 5 days | Drug: GS-6620<br>* GS-6620 tablet, 300 mg QD<br>|
| Other: Cohort 4<br>Cohort 4 (N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 100 mg GS 6620 or placebo QD in the morning without food (TDD = 100 mg) for 5 days | Drug: GS-6620<br>* GS-6620 tablet, 100 mg QD, Fasted<br>|
| Other: Cohort 5<br>Cohort 5 (N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 300 mg GS 6620 or placebo QD in the morning without food (TDD = 300 mg) for 5 days | Drug: GS-6620<br>* GS-6620 tablet, 300 mg QD, Fasted<br>|
| Other: Cohort 6<br>Cohort 6 (N = 10, genotype 2 or genotype 3): (Active drug: 8, Matching Placebo: 2) 900 mg GS 6620 or placebo QD in the morning without food (TDD = 900 mg) for 5 days | Drug: GS-6620<br>* GS-6620 tablet, 900 mg QD, Fasted<br>|
| Other: Cohort 7<br>Cohort 7 (N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 450 mg GS 6620 or placebo, administered BID with food (TDD = 900 mg) for 5 days | Drug: GS-6620 tablet, 450 mg BID<br>* GS-6620 tablet, 450 mg BID<br>|
| Other: Cohort 9<br>Cohort 9 (N = 10, genotype 1): (Active drug: 8, Matching Placebo: 2) 900 mg GS 6620 or placebo BID in the with food (TDD = 1800 mg) for 5 days | Drug: GS-6620 tablet<br>* GS-6620 tablet, 900mg , BID<br>|
| Other: Cohort 11<br>Cohort 11 (N = 10, genotype 1 : (Active drug: 8, Matching Placebo: 2) Up to 450 mg GS-6620 or placebo as an oral solution, BID, 12 hours apart in the fasted state, 2 hours after a meal (up to TDD = up to 900 mg) for 5 days. | Drug: GS-6620 tablet<br>* GS-6620 tablet, 900 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events as a measure of safety and tolerability. |  |  | 
| Number of subjects with HCV RNA viral response as a measure of antiviral activity. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations and pharmacokinetic parameters of GS-6620 and its metabolites will be measured. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C, HCV, HCV RNA, Polymerase inhibitor, Treatment naïve, GS-6620