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

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety, Tolerability and Antiviral Activity of GS-9688 in Virally-Suppressed Adult Subjects With Chronic Hepatitis B

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Selgantolimod; Drug: Hepatitis B virus (HBV) OAV Therapy; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand, 1010
    • Auckland Clinical Studies Limited
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Institute of Human Virology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 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 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selgantolimod 3 mg: HBeAg-positive CHB Participants; 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.	Drug: Selgantolimod; Tablet(s) administered orally once weekly; Other Names: GS-9688; Drug: Hepatitis B virus (HBV) OAV Therapy; Commercially available HBV OAV therapy could include one of the following: Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)
Experimental: Selgantolimod 3 mg: HBeAg-negative CHB Participants; 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.	Drug: Selgantolimod; Tablet(s) administered orally once weekly; Other Names: GS-9688; Drug: Hepatitis B virus (HBV) OAV Therapy; Commercially available HBV OAV therapy could include one of the following: Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)
Experimental: Selgantolimod 1.5 mg: HBeAg-positive CHB Participants; 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.	Drug: Selgantolimod; Tablet(s) administered orally once weekly; Other Names: GS-9688; Drug: Hepatitis B virus (HBV) OAV Therapy; Commercially available HBV OAV therapy could include one of the following: Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®); Drug: Placebo; Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly
Experimental: Selgantolimod 1.5 mg: HBeAg-negative CHB Participants; 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.	Drug: Selgantolimod; Tablet(s) administered orally once weekly; Other Names: GS-9688; Drug: Hepatitis B virus (HBV) OAV Therapy; Commercially available HBV OAV therapy could include one of the following: Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®); Drug: Placebo; Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly
Experimental: Placebo: HBeAg-positive CHB Participants; 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.	Drug: Hepatitis B virus (HBV) OAV Therapy; Commercially available HBV OAV therapy could include one of the following: Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®); Drug: Placebo; Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly
Experimental: Placebo: HBeAg-negative CHB Participants; 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.	Drug: Hepatitis B virus (HBV) OAV Therapy; Commercially available HBV OAV therapy could include one of the following: Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®); Drug: Placebo; Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Serum qHBsAg at Week 4		Baseline, Week 4
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 ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4		Week 4
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8		Week 8
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12		Week 12
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48		Week 48
Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 8		Baseline, Week 8
Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 12		Baseline, Week 12
Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 24		Baseline, Week 24
Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 48		Baseline, 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 HBeAb test changing from negative or 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 test changing from negative or 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 hepatitis B e antibody (HBeAb) test changing from negative or missing at baseline to positive at a postbaseline visit.	Week 48
Percentage of Participants With Virologic Breakthrough	Virologic breakthrough was defined as having two consecutive visits of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) ≥ 69 IU/mL.	Baseline up to Week 48
Percentage of Participants With Drug Resistance Mutations	The criteria for a drug resistance mutation was having two consecutive visits of HBV DNA ≥ 69 IU/mL.	Baseline up to Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Brooks AE, Verdon D, Eom J, Ng J, Steemson H, Lau AH, et al. Peripheral Immune Responses to Toll-Like Receptor 8 Agonist Selgantolimod (GS-9688) in Patients with Chronic Hepatitis B [Poster]. AASLD: The Liver Meeting® 2019; 2019 08-12 November; Boston, MA.
• Gane E, Zhao Y, Tan SK, Lau AH, Gaggar A, Subramanian M, et al. Efficacy and Safety of Oral TLR8 Agonist Selgantolimod in Virally Suppressed Adult Patients With Chronic Hepatitis B: a Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study [Poster 697]. AASLD: The Liver Meeting® 2019; 2019 08-12 November; Boston, MA.
• Chen DY, C. M, Tan SK, Yang JC, Gane EJ, Janssen HLA, et al. Characterization of Cytokine Response to Toll-Like Receptor 8 Agonist Selgantolimod in Viremic and Virally Suppressed Chronic Hepatitis B Patients [Poster 0721]. American Association for the Study of Liver Diseases (AASLD): The Liver Meeting Digital Experience; 2020 13-16 November.
• 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 FR1350]. The Digital International Liver Congress (ILC); 2020 27-29 August.
• Gane E, Dubar PR, Brooks AE, Zhao Y, Tan SK, Lau AH, et al. Efficacy and Safety of 24 Weeks Treatment with Oral TLR8 Agonist Selgantolimod (GS-9688, SLGN) in Virally Suppressed Adult Patients with Chronic Hepatitis B: A Phase 2 Study [Presentation]. The Digital International Liver Congress (ILC); 2020 27-29 August.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2018
• Primary Completion (Actual): March 22, 2019
• Study Completion (Actual): August 10, 2020

Study Registration Dates

• First Submitted: April 2, 2018
• First Submitted That Met QC Criteria: April 2, 2018
• First Posted (Actual): April 9, 2018

Study Record Updates

• Last Update Posted (Actual): August 19, 2021
• Last Update Submitted That Met QC Criteria: July 27, 2021
• Last Verified: July 1, 2021

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-389-2024; ACTRN12618000143224p (Registry Identifier: ANZCTR)

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