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

Study Overview
=================
Brief Summary
-----------------
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 or days 1-3 and 8-10. Follow-up visits are also required periodically through day 43, and potential viral load follow-up visits at weeks 3 and 6 months post last dose. Study procedures involve blood draws for pharmacokinetic, pharmacodynamic, virologic, and safety assessments

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

Conditions
-----------------
Hepatitis B, HBV

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chronic HBV infection ≥ 6 months HBsAg ≥ 250 IU/mL HBV treatment naïve 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
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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<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<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<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<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?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of adverse events in single and multiple oral doses of GS-9620 | Safety will be assessed during the study through the reporting of adverse events, by clinical laboratory tests, physical examinations including vital signs and ECGs at various time points during the study, and by documentation of concomitant medications throughout the study. | Periodically Through Week 25 | 

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) and multiple ascending dose (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]) | SAD Cohorts: whole blood and serum for pharmacodynamic (PD) assessments (RNA and cytokine analysis) will be drawn on Day 1: pre-dose and 8-hr post dose, Day 2, Day 3, Days 5 and 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 postdose, Day 2, Day 3, Day 5, and Day 8: pre-dose and 8 hours post-dose, Day 9, Day 10, Day 12, and Day 15 | Up to Day 15 | 
| Reduction of hepatitis B (HBV) viral load from baseline | Antiviral activity will be evaluated by determination of HBV HBsAg and HBV viral load kinetics | Up to Day 15 and Follow-Up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis, Hepatitis B, Hepatitis B Virus, HBV, GS-9620, Toll-like receptor (TLR)-7 Agonist