Study to Evaluate the Safety, Tolerability, and Antiviral Activity of Selgantolimod (Formerly GS-9688) in Viremic Adult Participants With Chronic Hepatitis B (CHB) Who Are Not Currently on Treatment

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis B

Treatments: Drug: Placebo; Drug: Selgantolimod; Drug: TAF

Study type: Interventional

Funder types: Industry

Identifiers

NCT03615066

GS-US-389-2025

Details and patient eligibility

About

The primary objectives of this study are to evaluate the safety and tolerability of multiple oral doses of selgantolimod and to evaluate the antiviral activity of selgantolimod in adult participants with chronic hepatitis B (CHB) who are viremic and not currently being treated.

Enrollment: 67 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 male and non-pregnant, non-lactating females
• Documented evidence of chronic hepatitis B virus (HBV) infection with detectable hepatitis B surface antigen (HBsAg) levels at screening
• Screening HBV deoxyribonucleic acid (DNA) ≥ 2000 international units per milliliter (IU/mL).
• Screening electrocardiogram (ECG) without clinically significant abnormalities

Key Exclusion Criteria:

• Extensive bridging fibrosis or cirrhosis

• Received a commercially available HBV OAV treatment(s) within the 3 months prior to screening.

• Received prolonged therapy with immunomodulators or biologics within 3 months of screening

• Individuals meeting any of the following laboratory parameters at screening:

  • Alanine aminotransferase > 5 * upper limit of normal (ULN)
  • International normalized ratio > ULN unless the individual is stable on an anticoagulant regimen
  • Albumin < 3.5 g/dL
  • Direct bilirubin >1.5x ULN
  • Platelet Count < 100,000/µL
  • Estimated creatinine clearance < 60 mL/min (using the Cockcroft-Gault method)

• Co-infection with human immunodeficiency virus (HIV), hepatitis C virus or hepatitis D virus

• Prior history of hepatocellular carcinoma 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.

• 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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67 participants in 3 patient groups, including a placebo group

Selgantolimod 3 mg + TAF

Experimental group

Description:

Participants with Hepatitis B e antigen (HBeAg)-positive CHB or HBeAg-negative CHB currently not on oral antiviral (OAV) treatment, will receive selgantolimod 3 mg (2 x 1.5 mg tablet) on the same day once weekly for 24 doses along with tenofovir alafenamide (TAF) 25 mg once daily for 24 weeks. After the 24th dose, selgantolimod will be discontinued, and participants will continue to receive TAF 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: TAF

Drug: Selgantolimod

Selgantolimod 1.5 mg + TAF

Experimental group

Description:

Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, will receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) and placebo (1 tablet) on the same day once weekly for 24 doses along with TAF 25 mg once daily for 24 weeks. After the 24th dose, selgantolimod will be discontinued, and participants will continue to receive TAF 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: TAF

Drug: Placebo

Drug: Selgantolimod

Placebo + TAF

Placebo Comparator group

Description:

Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, will receive 2 tablets of placebo on the same day once weekly for 24 doses along with TAF 25 mg once daily for 24 weeks. After the 24th dose, placebo will be discontinued, and participants will continue to receive TAF 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: TAF

Drug: Placebo