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

NCT ID: NCT03615066

Last Updated: 2022-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-28
• Study Completion Date: 2021-04-12

Brief Summary

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.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Selgantolimod 3 mg + TAF

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.

Group Type: EXPERIMENTAL

Selgantolimod

Intervention Type: DRUG

Tablet(s) administered orally every 7 days for 24 doses in fasted state

TAF

Intervention Type: DRUG

Tablet(s) administered orally once daily with food

Selgantolimod 1.5 mg + TAF

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Tablet(s) administered orally every 7 days for 24 doses in fasted state

Selgantolimod

Intervention Type: DRUG

Tablet(s) administered orally every 7 days for 24 doses in fasted state

TAF

Intervention Type: DRUG

Tablet(s) administered orally once daily with food

Placebo + TAF

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tablet(s) administered orally every 7 days for 24 doses in fasted state

TAF

Intervention Type: DRUG

Tablet(s) administered orally once daily with food

Interventions

Placebo

Tablet(s) administered orally every 7 days for 24 doses in fasted state

Intervention Type: DRUG

Selgantolimod

Tablet(s) administered orally every 7 days for 24 doses in fasted state

Intervention Type: DRUG

TAF

Tablet(s) administered orally once daily with food

Intervention Type: DRUG

Other Intervention Names

GS-9688; Vemlidy®

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 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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

University of Calgary Liver Unit - Heritage Medical Research Clinic

Calgary, Alberta, Canada

University Health Network, Toronto General Hospital, Toronto Centre for Liver Disease

Toronto, Ontario, Canada

Toronto Liver Centre

Toronto, Ontario, Canada

Seoul National University Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Chung-Ang University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

E-Da Hospital

Kaohsiung City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Countries

Canada; South Korea; Taiwan

References

Chen D, Kim S, Brooks A, McDonald C, Yang J, Gaggar A, et al. Potential Biomarkers of Response in Chronic Hepatitis B Patients Who Achieved HBeAg Loss Upon Treatment With Toll-Like Receptor 8 Agonist Selgantolimod [Poster]. The Digital International Liver Conference 2020 27-29 August.

Reference Type: BACKGROUND

Janssen H, Lampertico P, Chen C-Y, Heo J, Foumier C, Ahn S, et al. Safety and Efficacy of Switching to Tenofovir Alafenamide in Virally Suppressed Chronic Hepatitis B Patients With Renal Impairment: Week-48 Results From a Phase 2 Open-label Study [Poster]. The Digital International Liver Conference 2020 27-29 August.

Reference Type: BACKGROUND

Janssen H, Lim Y-S, Kim HJ, Tseng C-H, Coffin C, Elkashab M, et al. Safety and Efficacy of Oral TLR8 Agonist Selgantolimod in Viremic Adult Patients With Chronic Hepatitis B [Poster]. International Liver Congress 2021 23-26 June.

Reference Type: BACKGROUND

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GS-US-389-2025

Identifier Type: -

Identifier Source: org_study_id