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

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis B

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT03491553

GS-US-389-2024

ACTRN12618000143224p (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 48 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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48 participants in 6 patient groups

Selgantolimod 3 mg: HBeAg-positive CHB Participants

Experimental group

Description:

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.

Treatment:

Drug: Selgantolimod

Drug: Hepatitis B virus (HBV) OAV Therapy

Selgantolimod 3 mg: HBeAg-negative CHB Participants

Experimental group

Description:

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.

Treatment:

Drug: Selgantolimod

Drug: Hepatitis B virus (HBV) OAV Therapy

Selgantolimod 1.5 mg: HBeAg-positive CHB Participants

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Selgantolimod

Drug: Hepatitis B virus (HBV) OAV Therapy

Selgantolimod 1.5 mg: HBeAg-negative CHB Participants

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Selgantolimod

Drug: Hepatitis B virus (HBV) OAV Therapy

Placebo: HBeAg-positive CHB Participants

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Hepatitis B virus (HBV) OAV Therapy

Placebo: HBeAg-negative CHB Participants

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Hepatitis B virus (HBV) OAV Therapy