A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety, Tolerability and Antiviral Activity of GS-9688 in Virally-Suppressed Adult Subjects With Chronic Hepatitis B
Overview
- Phase
- Phase 2
- Intervention
- Selgantolimod
- Conditions
- Chronic Hepatitis B
- Sponsor
- Gilead Sciences
- Enrollment
- 48
- Locations
- 2
- Primary Endpoint
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The primary objectives of this study are to evaluate the safety, tolerability and antiviral activity of selgantolimod (formerly GS-9688) in virally suppressed chronic hepatitis B (CHB) adults on oral antiviral (OAV) agents.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
- •Adult males and non-pregnant, non-lactating females
- •Documented evidence of chronic HBV infection with detectable hepatitis B surface antigen (HBsAg) levels
- •On commercially available HBV OAV treatment(s) for at least 6 months with no change in regimen for 3 months prior to screening
- •HBV Deoxyribonucleic acid (DNA) ≤ 20 IU/mL for 6 or more months prior to screening
- •Screening Electrocardiogram (ECG) without clinically significant abnormalities
Exclusion Criteria
- •Extensive bridging fibrosis or cirrhosis
- •Adults meeting any of the protocol defined exclusionary laboratory parameters at screening:
- •Alanine aminotransferase (ALT) \> 3x Upper Limit of Normal (ULN)
- •International normalized ratio (INR) \> ULN unless the adult is stable on an anticoagulant regimen
- •Albumin \< 3.5 g/dL
- •Direct bilirubin \> 1.5x ULN
- •Platelet Count \< 100,000/uL
- •Estimated creatinine clearance \< 60 mL/min (using the Cockcroft-Gault method)
- •Co-infection with human immunodeficiency virus, hepatitis C virus or hepatitis D virus
- •Prior history of hepatocellular carcinoma (HCC) or screening alpha-fetoprotein ≥ 50 ng/mL without imaging
Arms & Interventions
Selgantolimod 3 mg: HBeAg-positive CHB Participants
Participants with Hepatitis B e Antigen (HBeAg)-positive CHB will remain on their current OAV and receive selgantolimod 3 mg (2 x 1.5 mg tablet) orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/early discontinuation (ED). At Week 48, per Principal Investigator's (PI's) discretion, participants can continue in the Treatment Free Follow-Up (TFFU) phase for up to an additional 48 weeks.
Intervention: Selgantolimod
Selgantolimod 3 mg: HBeAg-positive CHB Participants
Participants with Hepatitis B e Antigen (HBeAg)-positive CHB will remain on their current OAV and receive selgantolimod 3 mg (2 x 1.5 mg tablet) orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/early discontinuation (ED). At Week 48, per Principal Investigator's (PI's) discretion, participants can continue in the Treatment Free Follow-Up (TFFU) phase for up to an additional 48 weeks.
Intervention: Hepatitis B virus (HBV) OAV Therapy
Selgantolimod 3 mg: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 3 mg (2 x 1.5 mg tablet) orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
Intervention: Selgantolimod
Selgantolimod 3 mg: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 3 mg (2 x 1.5 mg tablet) orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
Intervention: Hepatitis B virus (HBV) OAV Therapy
Selgantolimod 1.5 mg: HBeAg-positive CHB Participants
Participants with HBeAg-positive CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
Intervention: Selgantolimod
Selgantolimod 1.5 mg: HBeAg-positive CHB Participants
Participants with HBeAg-positive CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
Intervention: Placebo
Selgantolimod 1.5 mg: HBeAg-positive CHB Participants
Participants with HBeAg-positive CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
Intervention: Hepatitis B virus (HBV) OAV Therapy
Selgantolimod 1.5 mg: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
Intervention: Selgantolimod
Selgantolimod 1.5 mg: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
Intervention: Placebo
Selgantolimod 1.5 mg: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
Intervention: Hepatitis B virus (HBV) OAV Therapy
Placebo: HBeAg-positive CHB Participants
Participants with HBeAg-positive CHB will remain on their current OAV and receive 2 tablets of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
Intervention: Placebo
Placebo: HBeAg-positive CHB Participants
Participants with HBeAg-positive CHB will remain on their current OAV and receive 2 tablets of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
Intervention: Hepatitis B virus (HBV) OAV Therapy
Placebo: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive 2 tablets of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
Intervention: Placebo
Placebo: HBeAg-negative CHB Participants
Participants with HBeAg-negative CHB will remain on their current OAV and receive 2 tablets of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.
Intervention: Hepatitis B virus (HBV) OAV Therapy
Outcomes
Primary Outcomes
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24
Time Frame: Week 24
Secondary Outcomes
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4(Week 4)
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8(Week 8)
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12(Week 12)
- Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48(Week 48)
- Change From Baseline in Serum qHBsAg at Week 4(Baseline, Week 4)
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 12(Week 12)
- Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 8(Baseline, Week 8)
- Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 12(Baseline, Week 12)
- Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 24(Baseline, Week 24)
- Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 48(Baseline, Week 48)
- Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12(Week 12)
- Percentage of Participants With HBsAg Loss at Week 24(Week 24)
- Percentage of Participants With HBsAg Loss at Week 48(Week 48)
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 24(Week 24)
- Percentage of Participants With HBeAg Loss and Seroconversion at Week 48(Week 48)
- Percentage of Participants With Virologic Breakthrough(Baseline up to Week 48)
- Percentage of Participants With Drug Resistance Mutations(Baseline up to Week 48)