Safety, Tolerability and Antiviral Activity of Selgantolimod in Virally-Suppressed Participants With Chronic Hepatitis B

Phase 2

Completed

Conditions: Chronic Hepatitis B

Interventions: Drug: Selgantolimod
Drug: Placebo
Drug: Hepatitis B virus (HBV) OAV Therapy

Registration Number: NCT03491553

Lead Sponsor: Gilead Sciences

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 48

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

Key

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
Diagnosis of autoimmune disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease, hemoglobinopathy, retinal disease, or are immunosuppressed.
Chronic liver disease of a non-HBV etiology, except for non-alcoholic fatty liver disease
Received solid organ or bone marrow transplant
Received prolonged therapy with immunomodulators or biologics within 3 months of screening
Use of another investigational agent within 90 days of screening, unless allowed by the Sponsor

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Selgantolimod 1.5 mg: HBeAg-positive CHB Participants	Placebo	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.
Selgantolimod 1.5 mg: HBeAg-negative CHB Participants	Placebo	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.
Placebo: HBeAg-negative CHB Participants	Hepatitis B virus (HBV) OAV Therapy	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.
Selgantolimod 1.5 mg: HBeAg-positive CHB Participants	Hepatitis B virus (HBV) OAV Therapy	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.
Placebo: HBeAg-positive CHB Participants	Hepatitis B virus (HBV) OAV Therapy	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.
Selgantolimod 3 mg: HBeAg-negative CHB Participants	Hepatitis B virus (HBV) OAV Therapy	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.
Placebo: HBeAg-negative CHB Participants	Placebo	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.
Selgantolimod 3 mg: HBeAg-positive CHB Participants	Hepatitis B virus (HBV) OAV Therapy	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.
Placebo: HBeAg-positive CHB Participants	Placebo	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.
Selgantolimod 1.5 mg: HBeAg-negative CHB Participants	Hepatitis B virus (HBV) OAV Therapy	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.
Selgantolimod 3 mg: HBeAg-negative CHB Participants	Selgantolimod	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.
Selgantolimod 1.5 mg: HBeAg-negative CHB Participants	Selgantolimod	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.
Selgantolimod 3 mg: HBeAg-positive CHB Participants	Selgantolimod	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.
Selgantolimod 1.5 mg: HBeAg-positive CHB Participants	Selgantolimod	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24	Week 24

Secondary Outcome Measures

Name	Time	Method
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
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	HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.
Percentage of Participants With HBsAg Loss at Week 24	Week 24	HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.
Percentage of Participants With HBsAg Loss at Week 48	Week 48	HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.
Percentage of Participants With HBeAg Loss and Seroconversion at Week 12	Week 12	HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as HBeAb test changing from negative or missing at baseline to positive at a postbaseline visit.
Percentage of Participants With HBeAg Loss and Seroconversion at Week 24	Week 24	HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as HBeAb test changing from negative or missing at baseline to positive at a postbaseline visit.
Percentage of Participants With HBeAg Loss and Seroconversion at Week 48	Week 48	HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as hepatitis B e antibody (HBeAb) test changing from negative or missing at baseline to positive at a postbaseline visit.
Percentage of Participants With Virologic Breakthrough	Baseline up to Week 48	Virologic breakthrough was defined as having two consecutive visits of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) ≥ 69 IU/mL.
Percentage of Participants With Drug Resistance Mutations	Baseline up to Week 48	The criteria for a drug resistance mutation was having two consecutive visits of HBV DNA ≥ 69 IU/mL.

Trial Locations

Locations (2): Auckland Clinical Studies Limited
🇳🇿
Auckland, New Zealand
University of Maryland, Institute of Human Virology
🇺🇸
Baltimore, Maryland, United States