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

NCT03615066 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: GS-US-389-2025
• Study Type: interventional
• Target: 67
• Locations: 3 countries
• Sites: 10

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

Outcome Measures

Primary Outcomes (3)

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

  Baseline, Week 24

• Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

  An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE was any unfavorable and unintended sign, symptom, disease, and/or laboratory or physiological observation that may or may not be related to the investigational medicinal product. A TEAE was defined as any AE with an onset date on or after the first dose date and no later than 30 days after permanent discontinuation of selgantolimod/placebo; or any AE leading to premature discontinuation of study drugs.

  First dose date up to Week 24 plus 30 days

• Percentage of Participants With Treatment-Emergent Laboratory Abnormalities

  Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of the last dose of study drug plus 30 days for selgantolimod/placebo at Week 24. If the relevant baseline laboratory value was missing, any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment emergent. Clinical laboratory results were graded according to Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities.

  First dose date up to Week 24 plus 30 days

Secondary Outcomes (28)

• Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4

  Baseline, Week 4

• Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8

  Baseline, Week 8

• Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12

  Baseline, Week 12

• Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48

  Baseline, Week 48

• Change From Baseline in Serum qHBsAg at Week 4

  Baseline, Week 4

Study Arms (3)

Selgantolimod 3 mg + TAF

EXPERIMENTAL

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.

Drug: Selgantolimod; Drug: TAF

Selgantolimod 1.5 mg + TAF

EXPERIMENTAL

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.

Drug: Placebo; Drug: Selgantolimod; Drug: TAF

Placebo + TAF

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: TAF

Interventions

Placebo DRUG

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

Placebo + TAF; Selgantolimod 1.5 mg + TAF

Selgantolimod DRUG

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

Also known as: GS-9688

Selgantolimod 1.5 mg + TAF; Selgantolimod 3 mg + TAF

TAF DRUG

Tablet(s) administered orally once daily with food

Also known as: Vemlidy®

Placebo + TAF; Selgantolimod 1.5 mg + TAF; Selgantolimod 3 mg + TAF

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (10)

University of Calgary Liver Unit - Heritage Medical Research Clinic

Calgary, Alberta, T2N4Z6, Canada

Location

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

Toronto, Ontario, M5G 2C4, Canada

Location

Toronto Liver Centre

Toronto, Ontario, M6H 3M1, Canada

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Chung-Ang University Hospital

Seoul, 06973, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 120-752, South Korea

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

E-Da Hospital

Kaohsiung City, 82445, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Related Publications (3)

• 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.

  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.

  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.

  BACKGROUND

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

selgantolimod; tenofovir alafenamide

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: August 3, 2018
• Study Start: August 28, 2018
• Primary Completion: December 12, 2019
• Study Completion: April 12, 2021
• Last Updated: May 10, 2022
• Results First Posted: January 6, 2021

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (4); CA (3); TW (3)