NCT04891770

Brief Summary

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).

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
103

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Aug 2021

Typical duration for phase_2

Geographic Reach
8 countries

26 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 14, 2021

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 18, 2021

Completed
3 months until next milestone

Study Start

First participant enrolled

August 14, 2021

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 23, 2024

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 19, 2024

Completed
1 year until next milestone

Results Posted

Study results publicly available

July 24, 2025

Completed
Last Updated

July 24, 2025

Status Verified

July 1, 2025

Enrollment Period

2.4 years

First QC Date

May 14, 2021

Results QC Date

July 7, 2025

Last Update Submit

July 7, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • Percentage of Participants With HBsAg Loss With and Without Anti-HBsAg Seroconversion

    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

    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

    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

    Up to 36 Weeks

Study Arms (3)

Cohort 1: TAF + VIR-2218 + SLGN + Nivolumab

EXPERIMENTAL

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 AlafenamideDrug: VIR-2218Drug: NivolumabDrug: Selgantolimod

Cohort 2 Group A: VIR-2218 + SLGN + Nivolumab

EXPERIMENTAL

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 AlafenamideDrug: VIR-2218Drug: NivolumabDrug: Selgantolimod

Cohort 2 Group B: SLGN + Nivolumab

EXPERIMENTAL

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 AlafenamideDrug: NivolumabDrug: Selgantolimod

Interventions

Administered as film-coated oral tablets

Also known as: TAF, Vemlidy®, GS-7340
Cohort 1: TAF + VIR-2218 + SLGN + NivolumabCohort 2 Group A: VIR-2218 + SLGN + NivolumabCohort 2 Group B: SLGN + Nivolumab

Administered as a sub-cutaneous (SC) injection

Cohort 1: TAF + VIR-2218 + SLGN + NivolumabCohort 2 Group A: VIR-2218 + SLGN + Nivolumab

Administered intravenously

Also known as: Opdivo®
Cohort 1: TAF + VIR-2218 + SLGN + NivolumabCohort 2 Group A: VIR-2218 + SLGN + NivolumabCohort 2 Group B: SLGN + Nivolumab

Administered as film-coated oral tablets

Also known as: SLGN, GS-9688
Cohort 1: TAF + VIR-2218 + SLGN + NivolumabCohort 2 Group A: VIR-2218 + SLGN + NivolumabCohort 2 Group B: SLGN + Nivolumab

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (26)

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Aalborg University Hospital

Aalborg, DK9000, Denmark

Location

Aarhus University Hospital

Aarhus N, 8200, Denmark

Location

Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

Odense University Hospital

Odense, DK5000, Denmark

Location

Princess Margaret Hospital (Hong Kong)

Hong Kong, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Alice Ho Miu Ling Nethersole Hospital

Tai Po, Hong Kong

Location

Auckland City Hospital

Grafton, 1010, New Zealand

Location

National University Hospital

Singapore, 119228, Singapore

Location

Changi General Hospital

Singapore, 529889, Singapore

Location

Singapore General Hospital

Singapore, Singapore

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul Saint Mary Hospital

Seoul, 06591, South Korea

Location

Chung-Ang University Hospital

Seoul, 06973, South Korea

Location

Yonsei University Severance Hospital

Seoul, 120-752, South Korea

Location

Korea University Guro Hospital

Seoul, 152-703, South Korea

Location

Thai Red Cross AIDS Research Centre (HIV-NAT)

Bangkok, 10330, Thailand

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Chiang Mai University, Maharaj Nakorn Chiang Mai Hospital

Muang, 50200, Thailand

Location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Related Publications (3)

  • 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.

    BACKGROUND
  • 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.

    BACKGROUND
  • 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.

    BACKGROUND

Related Links

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

tenofovir alafenamideNivolumabselgantolimod

Condition Hierarchy (Ancestors)

Hepatitis BBlood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Gilead Clinical Study Information Center
Organization
Gilead Sciences

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
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 14, 2021

First Posted

May 18, 2021

Study Start

August 14, 2021

Primary Completion

January 23, 2024

Study Completion

July 19, 2024

Last Updated

July 24, 2025

Results First Posted

July 24, 2025

Record last verified: 2025-07

Data Sharing

IPD Sharing
Will not share

Locations