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: Active, not recruiting
• 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 once daily for 36 weeks (up to 84 weeks).; VIR-2218 200 mg once every 4 weeks for 24 weeks. At Week 12 the following will be added: Selgantolimod (SLGN) 3 mg once a week on the same day for 24 weeks.; Nivolumab 0.3 mg/kg once every 4 weeks for up to 24 weeks (Up to protocol amendment 2). Participants who are on TAF treatment will continue TAF treatment over the duration of study follow-up. After the implementation of protocol amendment 2, nivolumab treatment was no longer administered.	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 once every 4 weeks for 24 weeks. At Week 12, the following will be added: SLGN 3 mg once a week on the same day for 24 weeks; Nivolumab 0.3 mg/kg once every 4 weeks for up to 24 weeks (Up to protocol amendment 2). Viremic participants who meet criteria to initiate NUC treatment will receive TAF 25 mg once daily for up to 36 weeks during the study. After the implementation of protocol amendment 2, nivolumab treatment was no longer administered.	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 once a week on the same day for 24 weeks.; Nivolumab 0.3 mg/kg once every 4 weeks for up to 24 weeks. Viremic participants who meet criteria to initiate NUC treatment will receive TAF 25 mg once daily for up to 36 weeks during the study. Cohort 2 Group B, all treatments were administered up to protocol amendment 2 and after the implementation of protocol amendment 2, the treatments were discontinued based on Sponsor decision due to low likelihood of efficacy.	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
Proportion of Participants Who Achieve Functional Cure	Functional cure is defined as hepatitis B surface antigen (HBsAg) loss and hepatitis B virus (HBV) DNA < lower limit of quantitation (LLOQ)	Up to Week 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With Hepatitis B Surface Antigen (HBsAg) Loss With and Without Anti-HBsAg Seroconversion		Up to 84 Weeks
Proportion 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		Up to 84 Weeks
Proportion of Participants Who Remain Off Nucleos(t)ide(s) (NUC) Treatment During Follow-Up		Week 36 up to Week 84
Proportion of Participants Experiencing Hepatitis B Virus (HBV) Virologic Breakthrough	Virologic breakthrough is 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.	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

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 (Estimated): July 1, 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): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; 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