A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety and Efficacy of GS-9620 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Subjects With Chronic Hepatitis B and Who Are Currently Not on Treatment
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Gilead Sciences
- Enrollment
- 192
- Primary Endpoint
- Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) From Baseline at Week 24
Study Overview
Brief Summary
The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of vesatolimod (formerly GS-9620) in adults with chronic hepatitis B (CHB) infection who are currently not being treated.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adult males or females between the ages of 18-65
- •Chronic hepatitis B virus (HBV) infection
- •HBV deoxyribonucleic acid (DNA ) ≥ 2000 IU/mL at screening
Exclusion Criteria
- •Extensive bridging fibrosis or cirrhosis
- •Received oral antiviral treatment for HBV or prolonged therapy with immune-modulators or biologics within 3 months of screening
- •Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV) or hepatitis D virus (HDV)
- •Chronic liver disease other than HBV
- •Lactating or pregnant females or those that wish to become pregnant during the course of the study
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Arms & Interventions
TDF + placebo
Main Study Phase: Tenofovir disoproxil fumarate (TDF) 300 mg tablets orally once daily for up to 48 weeks + placebo administered orally once a week (every 7 days) for 12 doses.
Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Intervention: TDF (Drug)
TDF + placebo
Main Study Phase: Tenofovir disoproxil fumarate (TDF) 300 mg tablets orally once daily for up to 48 weeks + placebo administered orally once a week (every 7 days) for 12 doses.
Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Intervention: Placebo (Drug)
TDF + Vesatolimod 1 mg
Main Study Phase:TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 1 mg tablet orally once a week (every 7 days) for 12 doses.
Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Intervention: TDF (Drug)
TDF + Vesatolimod 1 mg
Main Study Phase:TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 1 mg tablet orally once a week (every 7 days) for 12 doses.
Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Intervention: Vesatolimod (Drug)
TDF + Vesatolimod 2 mg
Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 2 mg tablet orally once a week (every 7 days) for 12 doses.
Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Intervention: TDF (Drug)
TDF + Vesatolimod 2 mg
Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 2 mg tablet orally once a week (every 7 days) for 12 doses.
Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Intervention: Vesatolimod (Drug)
TDF + Vesatolimod 4 mg
Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 4 mg tablet orally once a week (every 7 days) for 12 doses.
Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Intervention: TDF (Drug)
TDF + Vesatolimod 4 mg
Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 4 mg tablet orally once a week (every 7 days) for 12 doses.
Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.
Intervention: Vesatolimod (Drug)
Outcomes
Primary Outcomes
Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) From Baseline at Week 24
Time Frame: Baseline; Week 24
The change from baseline to Week 24 in HBsAg (log10 IU/mL) was analyzed using a mixed model for repeated measures (MMRM). The model included treatment, baseline HBsAg (log10 IU/mL), baseline Hepatitis B Envelope Antigen (HBeAg) status (positive or negative), baseline alanine aminotransferase (ALT) level relative to upper limit of normal (ULN) (\> 19 vs ≤ 19 IU/L for females; \> 30 vs ≤ 30 IU/L for males), visit and treatment-by-visit interaction as fixed effects, and visit as a repeated measure.
Secondary Outcomes
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 48(Week 48)
- Percentage of Participants With HBsAg Loss and Seroconversion at Week 24(Week 24)
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 24(Week 24)
- Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 48(Baseline; Week 48)
- Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 12(Baseline to Week 12)
- Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantitation (LLOQ) at Week 24(Week 24)
- Percentage of Participants With HBV DNA < LLOQ at Week 48(Week 48)
- Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase/Reverse Transcriptase (Pol/RT)(Baseline; Week 48)
- Pharmacokinetic (PK) Parameter: AUClast of Vesatolimod(Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose)
- Percentage of Participants With HBsAg Loss and Seroconversion at Week 48(Week 48)
- Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 12(Baseline; Week 12)
- Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 24(Baseline to Week 24)
- Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 48(Baseline to Week 48)
- Percentage of Participants Experiencing Virologic Breakthrough(Weeks 24 and 48)
- PK Parameter: AUCinf of Vesatolimod(Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose)
- PK Parameter: %AUCexp of Vesatolimod(Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose)
- PK Parameter: Cmax of Vesatolimod(Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose)
- PK Parameter: Clast of Vesatolimod(Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose)
- PK Parameter: Tmax of Vesatolimod(Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose)
- PK Parameter: Tlast of Vesatolimod(Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose)
- PK Parameter: T1/2 of Vesatolimod(Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose)
- PK Parameter: CL/F of Vesatolimod(Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose)