A Study Evaluating GS-9620 in Treatment Naive Subjects With Chronic Hepatitis C

Study Overview
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Brief Summary
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Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Dose escalation or repetition will be governed by pre-specified safety and activity rules. Subjects will be confined on either days 1-3 and/or days 8-10. Follow-up visits are also required periodically through day 43. Study procedures involve taking blood samples for pharmacokinetic, pharmacodynamic, virologic, and safety assessments.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled, Single and Multiple-Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antiviral Activity of GS-9620 in Treatment Naive Subjects With Chronic Hepatitis C Virus Infection

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Single Ascending Dose Cohorts GS-9620
* Drug: Multiple Ascending Dose Cohorts GS-9620


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and Females 18-65 years old Chronic HCV infection for at least 6 months, treatment naive HCV Viral load > 100,000 IU/mL at Screening Monoinfection with HCV 1 genotype Hepatitis B surface antigen negative Screening ECG without clinically significant abnormalities BMI 18-33 kg/m^2 Creatinine clearing > 70 mL/min Negative pregnancy test at screening Exclusion Criteria: Pregnant or lactating subjects Co-infection with hepatitis B virus (HBV) or HIV History of Gilberts disease Particular abnormal laboratory parameters Diagnosis of autoimmune disease, poorly controlled diabetes, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), malignancy, hemoglobinopathy, retinal disease, and those who are immunosuppressed Evidence of hepatocellular carcinoma On-going alcohol abuse Positive uring drug screen

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.3mg GS-9620<br> | Drug: Single Ascending Dose Cohorts GS-9620<br>* This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Subjects in Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.<br>|
| Experimental: 1mg GS-9620<br> | Drug: Single Ascending Dose Cohorts GS-9620<br>* This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Subjects in Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.<br>|
| Experimental: 2mg GS-9620<br> | Drug: Single Ascending Dose Cohorts GS-9620<br>* This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Subjects in Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.<br>|
| Experimental: 4mg GS-9620<br> | Drug: Single Ascending Dose Cohorts GS-9620<br>* This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Dose cohorts may be dosed with one of up to 4 possible total weekly doses (0.3 mg, 1 mg, 2 mg, 4 mg). Subjects in Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.<br>|
| Experimental: 0.3mg GS-9620 QW x 2 doses<br> | Drug: Multiple Ascending Dose Cohorts GS-9620<br>* This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Subjects in Multiple Ascending Dose (MAD) Cohorts will receive GS-9620 once weekly for two weeks (QW x 2 doses).<br>|
| Experimental: 1mg GS-9620 QW x 2 doses<br> | Drug: Multiple Ascending Dose Cohorts GS-9620<br>* This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Subjects in Multiple Ascending Dose (MAD) Cohorts will receive GS-9620 once weekly for two weeks (QW x 2 doses).<br>|
| Experimental: 2mg GS-9620 QW x 2 doses<br> | Drug: Multiple Ascending Dose Cohorts GS-9620<br>* This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Subjects in Multiple Ascending Dose (MAD) Cohorts will receive GS-9620 once weekly for two weeks (QW x 2 doses).<br>|
| Experimental: 4mg GS-9620 QW x 2 doses<br> | Drug: Multiple Ascending Dose Cohorts GS-9620<br>* This study will enroll cohorts of 6 eligible, unique subjects per cohort, randomized to either active drug or placebo (5:1) within each cohort. Subjects in Multiple Ascending Dose (MAD) Cohorts will receive GS-9620 once weekly for two weeks (QW x 2 doses).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events in single and multiple doses of GS-9620 | Assessments include adverse events, laboratory abnormalities, 12-lead ECG abnormalities and interval measurements, and vital sign measurements | Periodically Day 1 to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of plasma drug concentrations of GS-9620 using non-compartmental methods | Single ascending dose (SAD) cohorts: serial blood samples will be collected on Day 1 at 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 48, and 96 hours post-dose. Multiple ascending dose (MAD) cohorts: serial blood samples will be collected on Day 8 at 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, and 24 hours post-dose. | Day 1 and Day 8 | 
| Measurement of pharmacodynamic markers (cytokines and interferon-stimulated genes [ISGs]) | SAD cohorts: Whole blood and serum for pharmacodynamic (PD) assessments (RNA and cytokine analysis) will be drawn on Day 1: Pre-dose and 8-hour Post-dose, Day 2, Day 3, Day 5, Day 8 MAD cohorts: Whole blood and serum for PD assessments (RNA and cytokine analysis) will be drawn on Day 1: Pre-dose and 8-hours Post-dose, Day 2, Day 3, Day 5, Day 8: Pre-dose and 8 hours Post-dose, Day 9, Day 10, Day 12, and Day 15 | Days 1, 2, 3, 5, 8 | 
| Reduction of hepatitis C (HCV) RNA viral load from baseline | SAD cohorts: HCV viral load will be drawn at Day 1: Pre-dose, Day 2, 3, 5, 8 and both Follow-up Visits. MAD cohorts: HCV viral load will be drawn at Day 1: Pre-dose, Day 2, 3, 5, Day 8: Pre-dose, 9, 10, 15, and both Follow-Up Visits. | Screening, Baseline, Day 8 or 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic HCV, HCV, Treatment Naive, Gilead, GS-9620, Hepatitis, Hepatitis C