A Study Evaluating GS-9620 in Virologically Suppressed Subjects With Chronic Hepatitis B Virus Infection

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 days 1-3 and/or days 8-10. Follow-up visits are required periodically through day 43. Subjects with sustained reductions in HbsAg will be requested to return for additional follow-up follow-up visits at 3 and 6 months post last dose. Study procedures involve blood draws 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 Virologically Suppressed Subjects With Chronic Hepatitis B Virus Infection

Conditions
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Hepatitis B

Intervention / Treatment
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* Drug: Single Ascending Dose (SAD) Cohorts GS-9620
* Drug: Multiple Ascending Dose (MAD) Cohorts GS-9620


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic HBV infection for ≥ 6 months Currently on treatment with at least 1 HBV approved oral drug (i.e. lamivudine, telbivudine, entecavir, adefovir, tenofovir) ≥ 3 months prior to screening HBsAg ≥ 250 IU/mL HBV DNA at below the level of quantitation (BLQ; to be confirmed at screening) Absence of extensive bridging fibrosis (Metavir 3 or greater)or cirrhosis Creatinine clearance ≥ 70 mL/min Exclusion Criteria: Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), or HIV History of Gilberts disease Laboratory parameters not within defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, thyroid-stimulating hormone (TSH), or other evidence of hepatic decompensation Diagnosis of autoimmune disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), malignancy, hemoglobinopathy, retinal disease, or patients who are immunosuppressed Evidence of hepatocellular carcinoma

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 (SAD) 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 Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.<br>|
| Experimental: 1mg GS-9620<br> | Drug: Single Ascending Dose (SAD) 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 Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.<br>|
| Experimental: 2mg GS-9620<br> | Drug: Single Ascending Dose (SAD) 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 Single Ascending Dose (SAD) Cohorts will receive a single dose of GS-9620.<br>|
| Experimental: 4mg GS-9620<br> | Drug: Single Ascending Dose (SAD) 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 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 (MAD) 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 (MAD) 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 (MAD) 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 (MAD) 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 |
| --- | --- | --- |
| Assessment of adverse events in single and multiple oral doses of GS-9620 | Assessments include adverse events, laboratory abnormalities, 12-lead ECG abnormalities and interval measurements, and vital signs 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 | SAD and MAD 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. Mad Cohorts: serial blood samples will also 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]) | Single ascending dose (SAD) Cohorts: Whole blood and serum for pharmacodynamic (PD) assessments (RNA and cytokine analysis) will be drawn on Day 1 at pre-dose, 8, 24 and 48 hours post-dose, and on Days 5 and Day 8 Multiple ascending dose (MAD) Cohorts: Whole blood and serum for PD assessments (RNA and cytokine analysis) will be drawn on Day 1: Pre-dose and 8 hours Postdose, Day 2, Day 3, and Day 5 Day 8: Pre-dose and 8 hours Post-dose, Day 9, 10, 12, and Day 15 | Days 1, 2, 3, 5, 8 | 
| Reduction of hepatitis B (HBV) viral load from baseline | SAD cohort: HBsAg+ levels will be drawn at Day 1: Pre-dose, Day 2, 3, 5, 8 and both Follow-up Visits. MAD cohorts: HBsAg+ levels 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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Hepatitis, Hepatitis B, Hepatitis B Virus, HBV, GS-9620, Toll-like receptor (TLR)-7 Agonist