Study to Evaluate the Safety and Efficacy of Selgantolimod (SLGN)-Containing Combination Therapies for the Treatment of Chronic Hepatitis B (CHB)

A Phase 2a, Open-Label Study to Evaluate the Safety and Efficacy of Selgantolimod (SLGN)-Containing Combination Therapies for the Treatment of Chronic Hepatitis B (CHB)

The primary objectives of this study are to evaluate the safety and tolerability of study treatment(s) (selgantolimod-containing combination therapies) and to evaluate the efficacy of study treatment(s) as measured by the proportion of participants who achieve functional cure, defined as hepatitis B surface antigen (HBsAg) loss and hepatitis B virus (HBV)deoxyribonucleic acid (DNA) < lower limit of quantitation (LLOQ) at Follow-up (FU) Week 24 in participants with chronic hepatitis B (CHB).

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Tenofovir Alafenamide; Drug: VIR-2218; Drug: Nivolumab; Drug: Selgantolimod

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Denmark
  • Aalborg, Denmark, DK9000
    • Aalborg University Hospital
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital
  • Odense, Denmark, DK5000
    • Odense University Hospital
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Princess Margaret Hospital (Hong Kong)
  • Shatin, Hong Kong
    • Prince of Wales Hospital
  • Tai Po, Hong Kong
    • Alice Ho Miu Ling Nethersole Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 152-703
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06973
    • Chung-Ang University Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University Severance Hospital
  • Seoul, Korea, Republic of, 06591
    • Seoul Saint Mary Hospital
• New Zealand
  • Grafton, New Zealand, 1010
    • Auckland City Hospital
• Singapore
  • Singapore, Singapore
    • Singapore General Hospital
  • Singapore, Singapore, 529889
    • Changi General Hospital
  • Singapore, Singapore, 119228
    • National University Hospital
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Bangkok, Thailand, 10330
    • Thai Red Cross AIDS Research Centre (HIV-NAT)
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital
  • Muang, Thailand, 50200
    • Chiang Mai University, Maharaj Nakorn Chiang Mai Hospital
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Willing and able to provide informed consent
• Chronic HBV infection for at least 6 months
• Willing to follow protocol-specified contraception requirement

Key Exclusion Criteria:

• Have extensive fibrosis or cirrhosis in the liver
• Have or had liver cancer (hepatocellular carcinoma)
• Have an autoimmune disease
• Have chronic liver disease other than HBV
• Females who are breastfeeding, pregnant, or who wish to become pregnant during the study

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: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: TAF + VIR-2218 + SLGN + Nivolumab; Nucleos(t)ide(s) (NUC)-suppressed participants with chronic hepatitis B (CHB) will receive tenofovir alafenamide (TAF) 25 mg orally once daily (QD) for 36 weeks and VIR-2218 200 mg subcutaneously (SC) once every 4 weeks (Q4W) for 24 weeks. From Week 12 onwards, participants will receive selgantolimod (SLGN) 3 mg orally once a week (QW) for 24 weeks and nivolumab 0.3 mg/kg intravenously (IV) Q4W for up to 24 weeks (only up to protocol amendment 2, nivolumab was no longer administered post implementation of protocol amendment 2). Participants who are on TAF treatment will continue TAF treatment over the duration of study follow-up. Participants will be followed up for 48 weeks post treatment.	Drug: Tenofovir Alafenamide; Administered as film-coated oral tablets; Other Names: Vemlidy®; GS-7340; TAF; Drug: VIR-2218; Administered as a sub-cutaneous (SC) injection; Drug: Nivolumab; Administered intravenously; Other Names: Opdivo®; Drug: Selgantolimod; Administered as film-coated oral tablets; Other Names: SLGN; GS-9688
Experimental: Cohort 2 Group A: VIR-2218 + SLGN + Nivolumab; Viremic participants with CHB will receive VIR-2218, 200 mg SC Q4W for 24 weeks. From Week 12 onwards, participants will receive SLGN 3 mg orally QW for 24 weeks and nivolumab 0.3 mg/kg IV Q4W for up to 24 weeks (only up to protocol amendment 2, nivolumab was no longer administered post implementation of protocol amendment 2). Participants who meet the criteria to initiate NUC treatment will receive TAF 25, mg orally, QD during the study. Participants will be followed up for 48 weeks post treatment.	Drug: Tenofovir Alafenamide; Administered as film-coated oral tablets; Other Names: Vemlidy®; GS-7340; TAF; Drug: VIR-2218; Administered as a sub-cutaneous (SC) injection; Drug: Nivolumab; Administered intravenously; Other Names: Opdivo®; Drug: Selgantolimod; Administered as film-coated oral tablets; Other Names: SLGN; GS-9688
Experimental: Cohort 2 Group B: SLGN + Nivolumab; Viremic participants with CHB will receive SLGN 3 mg orally QW for 24 weeks and nivolumab 0.3 mg/kg IV Q4W for up to 24 weeks. . Viremic participants who meet the criteria to initiate NUC treatment will receive TAF 25 mg orally QD during the study. Participants will be followed up for 48 weeks post treatment. All treatments were administered up to protocol amendment 2 and after the implementation of protocol amendment 2, the treatments were discontinued for Cohort 2 Group B based on Sponsor decision.	Drug: Tenofovir Alafenamide; Administered as film-coated oral tablets; Other Names: Vemlidy®; GS-7340; TAF; Drug: Nivolumab; Administered intravenously; Other Names: Opdivo®; Drug: Selgantolimod; Administered as film-coated oral tablets; Other Names: SLGN; GS-9688

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Functional Cure	Functional cure was defined as hepatitis B surface antigen (HBsAg) loss and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) less than the lower limit of quantitation (LLOQ) at follow-up Week 24. LLOQ for HBV DNA CAP/CTM 2.0 is 20 IU/mL. LLOQ for HBV DNA Cobas 6800 is 10 IU/mL. The HBsAg loss was defined as HBsAg changing from positive at baseline to negative at any postbaseline visit. Percentages were rounded off.	At Follow-up Week 24 (Cohort 1 and Cohort 2A: At Week 60; Cohort 2B: At Week 48)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HBsAg Loss With and Without Anti-HBsAg Seroconversion	HBsAg loss was defined as HBsAg changing from positive at baseline to negative at any postbaseline visit. HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative/missing at baseline to positive at a postbaseline visit. Percentages were rounded-off.	Up to Follow-up Week 48 (Cohort 1 and Cohort 2A: At Week 84; Cohort 2B: At Week 72)
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss With and Without Anti-HBeAg Seroconversion in Participants With CHB Who Are HBeAg-Positive at Baseline	HBeAg loss is defined as HBeAg changing from positive at baseline to negative at any postbaseline visit. HBeAg seroconversion was defined as HBeAb test changing from negative or missing at baseline to positive at a postbaseline visit. Percentages were rounded-off.	Up to Follow-up Week 48 (Cohort 1 and Cohort 2A: At Week 84; Cohort 2B: At Week 72)
Percentage of Participants Who Remain Off NUC Treatment During Follow-Up	NUC treatments included for analysis: adefovir dipivoxil, entecavir, telbivudine, tenofovir, tenofovir alafenamide, tenofovir alafenamide fumarate, tenofovir disoproxil fumarate, and lamivudine. Percentages were rounded-off.	Cohort 1 and Cohort 2A: From Week 36 up to Week 84 and for Cohort 2B: From Week 24 up to Week 72
Percentage of Participants Experiencing Hepatitis B Virus (HBV) Virologic Breakthrough During Study Treatments	Virologic breakthrough was defined as confirmed HBV DNA ≥ LLOQ after 2 consecutive HBV DNA < LLOQ in participants who are complying with NUC therapy or confirmed HBV DNA ≥ 1 log10 IU/mL increase from nadir during study treatments. LLOQ for HBV DNA CAP/CTM 2.0 is 20 IU/mL. LLOQ for HBV DNA Cobas 6800 is 10 IU/mL. Percentages were rounded-off.	Up to 36 Weeks

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Vir Biotechnology, Inc.
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Wong GL, Lim SG, Agarwal K, Avihingsanon A, Lim Y, et al. Results From a Phase 2a, Open-Label Study to Evaluate the Safety and Efficacy of Novel Combination Therapies Containing VIR-2218, Selgantolimod, and Nivolumab for the Treatment of Chronic Hepatitis B. Poster #1380; Presented at The Liver Meeting, American Association for the Study of Liver Diseases; 2024 November 15-19; San Diego, CA.
• Pan D, Kolhatkar N, Sowah L, Arizpe A, Cloutier D, et al. Immunologic Biomarker Dynamics in Chronic Hepatitis B: Insights From a Phase 2a Open-Label Study on Combination Therapies With Small Interfering RNA, Selgantolimod, and Nivolumab. Poster #1134; Presented at The Liver Meeting, American Association for the Study of Liver Diseases; 2024 November 15-19; San Diego, CA.
• Gane EJ, Tanwandee T, Yi B, Chew T, Botros I, et al. Immune-Related Adverse Events With Low-Dose Nivolumab in Patients With Chronic Hepatitis B: Experience From 3 Clinical Studies. Poster #1332; Presented at The Liver Meeting, American Association for the Study of Liver Diseases; 2024 November 15-19; San Diego, CA.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2021
• Primary Completion (Actual): January 23, 2024
• Study Completion (Actual): July 19, 2024

Study Registration Dates

• First Submitted: May 14, 2021
• First Submitted That Met QC Criteria: May 14, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Actual): July 24, 2025
• Last Update Submitted That Met QC Criteria: July 7, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis A; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Hepatitis, Chronic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Nivolumab
• Other Study ID Numbers: GS-US-465-4439; 2021-000672-11 (EudraCT Number)

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