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

Gilead Sciences49 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Hepatitis B HBV

Interventions

Single Ascending Dose (SAD) Cohorts GS-9620DRUG

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.

Multiple Ascending Dose (MAD) CohortsDRUG

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)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (23)

Mayo Clinic Hospital

Phoenix, Arizona, United States

Outcomes

Primary Outcomes

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.

Time frame: Periodically Through Week 25

Secondary Outcomes

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.

Time frame: 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

Time frame: 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

Time frame: Up to Day 15 and Follow-Up

Data from ClinicalTrials.gov

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