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

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety, Tolerability and Antiviral Activity of GS-9688 in Viremic Adult Subjects With Chronic Hepatitis B Who Are Not Currently on Treatment

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Selgantolimod; Drug: TAF; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4Z6
      • University of Calgary Liver Unit - Heritage Medical Research Clinic
  • Ontario
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Centre
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network, Toronto General Hospital, Toronto Centre for Liver Disease
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06973
    • Chung-Ang University Hospital
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei University Health System
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung City, Taiwan, 82445
    • E-DA hospital
  • Taipei City, Taiwan, 10002
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Selgantolimod; Tablet(s) administered orally every 7 days for 24 doses in fasted state; Other Names: GS-9688; Drug: TAF; Tablet(s) administered orally once daily with food; Other Names: Vemlidy®
Experimental: 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.	Drug: Selgantolimod; Tablet(s) administered orally every 7 days for 24 doses in fasted state; Other Names: GS-9688; Drug: TAF; Tablet(s) administered orally once daily with food; Other Names: Vemlidy®; Drug: Placebo; Tablet(s) administered orally every 7 days for 24 doses in fasted state
Placebo Comparator: 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.	Drug: TAF; Tablet(s) administered orally once daily with food; Other Names: Vemlidy®; Drug: Placebo; Tablet(s) administered orally every 7 days for 24 doses in fasted state

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Change From Baseline in Serum qHBsAg at Week 8		Baseline, Week 8
Change From Baseline in Serum qHBsAg at Week 12		Baseline, Week 12
Change From Baseline in Serum qHBsAg at Week 24		Baseline, Week 24
Change From Baseline in Serum qHBsAg at Week 48		Baseline, Week 48
Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < Lower Limit of Quantification (LLOQ) at Week 12	LLOQ was defined as 20 IU/mL.	Week 12
Percentage of Participants With HBV DNA < LLOQ at Week 24	LLOQ was defined as 20 IU/mL.	Week 24
Percentage of Participants With HBV DNA < LLOQ at Week 48	LLOQ was defined as 20 IU/mL.	Week 48
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12	HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.	Week 12
Percentage of Participants With HBsAg Loss at Week 24	HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.	Week 24
Percentage of Participants With HBsAg Loss at Week 48	HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.	Week 48
Percentage of Participants With HBeAg Loss and Seroconversion at 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 Hepatitis B e antibody (HBeAb) loss and anti-HBe change from negative/missing at baseline to positive at a postbaseline visit.	Week 12
Percentage of Participants With HBeAg Loss and Seroconversion at 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 loss and anti-HBe change from negative/missing at baseline to positive at a postbaseline visit.	Week 24
Percentage of Participants With HBeAg Loss and Seroconversion at 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 HBeAb test changing from negative or missing at baseline to positive at a postbaseline visit.	Week 48
Percentage of Participants With Virologic Breakthrough From Baseline up to Week 24	Virologic breakthrough was defined as confirmed HBV DNA ≥ 69 IU/mL after having been < 69 IU/mL or confirmed HBV DNA ≥ 1 log10 IU/mL increase from nadir.	Baseline up to Week 24
Percentage of Participants With Virologic Breakthrough From Baseline up to Week 48	Virologic breakthrough was defined as confirmed HBV DNA ≥ 69 IU/mL after having been < 69 IU/mL or confirmed HBV DNA ≥ 1 log10 IU/mL increase from nadir.	Baseline up to Week 48
Percentage of Participants With Drug Resistance Mutations		Baseline up to Week 48
Pharmacokinetic (PK) Parameter: AUClast of Selgantolimod	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
PK Parameter: AUC0-24 of Selgantolimod	AUC0-24 is defined as the concentration of drug over time from time zero to time 24 hours.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
PK Parameter: AUCinf of Selgantolimod	AUC0-inf is defined as the concentration of drug over time from time zero to infinity.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
PK Parameter: Cmax of Selgantolimod	Cmax is defined as the maximum concentration of drug.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
PK Parameter: Tmax of Selgantolimod	Tmax is defined as the time (observed time point) of Cmax.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
PK Parameter: CL/F of Selgantolimod	CL/F is defined as the apparent oral clearance following administration of the drug.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
PK Parameter: t1/2 of Selgantolimod	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2018
• Primary Completion (Actual): December 12, 2019
• Study Completion (Actual): April 12, 2021

Study Registration Dates

• First Submitted: July 30, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: GS-US-389-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes