A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety and Efficacy of GS-9620 for the Treatment of Virally-Suppressed Subjects With Chronic Hepatitis B
Overview
- Phase
- Phase 2
- Intervention
- Vesatolimod
- Conditions
- Chronic Hepatitis B
- Sponsor
- Gilead Sciences
- Enrollment
- 162
- Primary Endpoint
- Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of vesatolimod in participants with chronic hepatitis B (CHB) infection currently being treated with oral antivirals (OAV).
Participants will be randomized in 3 sequential cohorts (Cohorts A, B, and C). Within each cohort, participants will be randomized in a 1:3:3:3 ratio to placebo or one of the doses of vesatolimod (1, 2, or 4 mg).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
- •Documented evidence of CHB infection (eg, hepatitis B surface antigen \[HBsAg\] positive for more than 6 months) with detectable HBsAg levels at screening
- •Have been on approved HBV OAV treatment for ≥ 1 year prior to screening, with HBV DNA below lower limit of quantitation (LLOQ), measured at least once, 6 or more months prior to screening, and HBV DNA \< 20 IU/mL at screening
- •Currently taking an approved HBV OAV (tenofovir, entecavir, adefovir, lamivudine, or telbivudine, either as single agents or in combination) with no change in regimen for 3 months prior to screening
- •Willing to provide blood sample for toll-like receptor 7 (TLR-7) and interleukin 28 B (IL28B) single-nucleotide polymorphism (SNP) assessment
- •Must be willing and able to comply with all study requirements
Exclusion Criteria
- •Extensive bridging fibrosis or cirrhosis
- •Laboratory parameters not within defined thresholds for neutropenia, anemia, thrombocytopenia, leukopenia, or other evidence of inadequate liver function
- •Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV)
- •Evidence of hepatocellular carcinoma
- •Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Participants under evaluation for possible malignancy are not eligible.
- •Significant cardiovascular, pulmonary, or neurological disease
- •Any of the following conditions that may worsen in response to interferon (IFN):
- •Autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, moderate or severe psoriasis)
- •Poorly controlled diabetes mellitus
- •Significant psychiatric disorders
Arms & Interventions
Vesatolimod 4 mg 4 Weeks (Cohort A)
Vesatolimod 4 mg tablet once a week for 4 weeks
Intervention: Vesatolimod
Placebo 4 Weeks (Cohort A)
Placebo tablet once a week for 4 weeks
Intervention: Placebo
Vesatolimod 1 mg 4 Weeks (Cohort A)
Vesatolimod 1 mg tablet once a week for 4 weeks
Intervention: Vesatolimod
Vesatolimod 2 mg 4 Weeks (Cohort A)
Vesatolimod 2 mg tablet once a week for 4 weeks
Intervention: Vesatolimod
Placebo 8 Weeks (Cohort B)
Placebo tablet once a week for 8 weeks
Intervention: Placebo
Vesatolimod 1 mg 8 Weeks (Cohort B)
Vesatolimod 1 mg tablet once a week for 8 weeks
Intervention: Vesatolimod
Vesatolimod 2 mg 8 Weeks (Cohort B)
Vesatolimod 2 mg tablet once a week for 8 weeks
Intervention: Vesatolimod
Vesatolimod 4 mg 8 Weeks (Cohort B)
Vesatolimod 4 mg tablet once a week for 8 weeks
Intervention: Vesatolimod
Placebo 12 Weeks (Cohort C)
Placebo tablet once a week for 12 weeks
Intervention: Placebo
Vesatolimod 1 mg 12 Weeks (Cohort C)
Vesatolimod 1 mg tablet once a week for 12 weeks
Intervention: Vesatolimod
Vesatolimod 2 mg 12 Weeks (Cohort C)
Vesatolimod 2 mg tablet once a week for 12 weeks
Intervention: Vesatolimod
Vesatolimod 4 mg 12 Weeks (Cohort C)
Vesatolimod 4 mg tablet once a week for 12 weeks
Intervention: Vesatolimod
Outcomes
Primary Outcomes
Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24
Time Frame: Baseline to Week 24
A mixed effect model for repeated measures (MMRM) was used to analyze HBsAg change from baseline, which included treatment, baseline HBsAg level (\> 5000 IU/mL or ≤ 5000 IU/mL), HBeAg baseline status (positive or negative), visit and treatment-by-visit interaction as fixed effect and visit as repeated measurement.
Secondary Outcomes
- Change From Baseline in Serum HBsAg Level at Week 12(Baseline; Week 12)
- Change From Baseline in Serum HBsAg Level at Week 48(Baseline; Week 48)
- Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24(Week 24)
- Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24(Week 24)
- Change From Baseline in Serum HBsAg Level at Week 4(Baseline; Week 4)
- Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48(Week 48)
- Change From Baseline in Serum HBsAg Level at Week 8(Baseline; Week 8)
- Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48(Week 48)