HBV, Hepatitis B
Conditions
Keywords
Hepatitis, Hepatitis B, Hepatitis B Virus, HBV, GS-9620, Toll-like receptor (TLR)-7 Agonist
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
Interventions
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.
DRUGMultiple Ascending Dose (MAD) Cohorts
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)
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of adverse events in single and multiple oral doses of GS-9620 | Periodically Through Week 25 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of plasma drug concentrations of GS-9620 using non-compartmental methods | Day 1 and Day 8 | 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. |
| Measurement of pharmacodynamic markers (cytokines and interferon-stimulated genes [ISGs]) | Up to Day 15 | 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 |
| Reduction of hepatitis B (HBV) viral load from baseline | Up to Day 15 and Follow-Up | Antiviral activity will be evaluated by determination of HBV HBsAg and HBV viral load kinetics |
Countries
Australia, Canada, New Zealand, South Korea, United States
Outcome results
None listed