Study to Investigate the Safety and Efficacy of BRII-835 and BRII-179 Combination Therapy Treating Chronic Hepatitis B Virus (HBV) Infection

A Phase 2 Multicenter, Randomized, Open-label Study to Investigate the Safety and Efficacy of BRII-835 (VIR-2218) and BRII-179 (VBI-2601) Combination Therapy for the Treatment of Chronic Hepatitis B Virus (HBV) Infection

This is an open label, randomized, parallel-group study to evaluate the safety and efficacy of combination treatment BRII-835 (VIR-2218) and BRII-179 (VBI-2601) in adult participants with chronic HBV infection

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: BRII-835 (VIR-2218); Biological: BRII-179 (VBI-2601) with IFN-α; Biological: BRII-179 (VBI-2601)

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Investigative Site 61002
    • Westmead, New South Wales, Australia, 2145
      • Investigative Site 61001
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Investigative Site 61004
• China
  • Changhua, Taiwan, China, 500
    • Investigative Site 88602
  • Hong Kong, China
    • Investigative Site 85201
  • Hong Kong, China
    • Investigative Site 85202
  • Hong Kong, China
    • Investigative Site 85203
  • Kaohsiung, Taiwan, China, 83301
    • Investigative Site 88601
  • Kaohsiung, Taiwan, China
    • Investigative Site 88604
  • NEW Territories, Hong Kong, China
    • Investigative Site 85204
  • Taichung, Taiwan, China, 40447
    • Investigative Site 88603
  • Taipei CITY, China, 10048
    • Investigative Site 88605
• New Zealand
  • Auckland, New Zealand, 2025
    • Investigative Site 64001
  • Dunedin
    • Dunedin Central, Dunedin, New Zealand, 9016
      • Investigative Site 64002
• Singapore
  • Singapore, Singapore, 169608
    • Investigative Site 65001
  • Singapore, Singapore, 529889
    • Investigative Site 65002
• South Korea
  • Busan, South Korea, 49241
    • Investigative Site 82004
  • Seongnam-si, Gyeonggi-do, South Korea, 13496
    • Investigative Site 82003
  • Seoul, South Korea, 3080
    • Investigative Site 82001
  • Seoul, South Korea, 3722
    • Investigative Site 82005
  • Seoul, South Korea, 5505
    • Investigative Site 82002
• Thailand
  • Bangkok, Thailand, 10330
    • Investigative Site 66001
  • Chiang Mai, Thailand, 50200
    • Investigative Site 66003
  • Khon Kaen, Thailand, 40002
    • Investigative Site 66002
  • Nonthaburi, Thailand, 11000
    • Investigative Site 66005
  • Nonthaburi, Thailand, 11000
    • Investigative Site 66006
  • Pathum Thani, Thailand, 12120
    • Investigative Site 66004
  • Songkhla, Thailand, 90110
    • Investigative Site 66007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female aged 18 - 60
• Body mass index ≥ 18 kg/m^2 and ≤ 32 kg/m^2
• Chronic HBV infection as defined by a positive serum HBsAg for ≥ 6 months

Exclusion Criteria:

• Any clinically significant chronic or acute medical condition that makes the volunteer unsuitable for participation
• Significant fibrosis or cirrhosis
• History or evidence of drug or alcohol abuse
• History of intolerance to SC or IM injection
• History of chronic liver disease from any cause other than chronic HBV infection
• History of hepatic decompensation

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 A; Participants will receive BRII-835 (VIR-2218) for 32 weeks	Drug: BRII-835 (VIR-2218); BRII-835 (VIR-2218) will be given by subcutaneous injection
Experimental: Cohort B; Participants will receive BRII-835 (VIR-2218) and BRII-179 (VBI-2601) with IFN-α up to Week 40	Drug: BRII-835 (VIR-2218); BRII-835 (VIR-2218) will be given by subcutaneous injection; Biological: BRII-179 (VBI-2601) with IFN-α; BRII-179 (VBI-2601) with IFN-α will be co-administered by intramuscular injection
Experimental: Cohort C; Participant will receive BRII-835 (VIR-2218) and BRII-179 (VBI-2601) up to Week 40	Drug: BRII-835 (VIR-2218); BRII-835 (VIR-2218) will be given by subcutaneous injection; Biological: BRII-179 (VBI-2601); BRII-179 (VBI-2601) will be administered by intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained HBsAg Loss During the 48-week Follow-up Period After NRTI Withdrawal	Sustained HBsAg loss was defined as undetectable HBsAg < 0.05 IU/mL for at least 24 weeks during the 48-week follow-up period after NRTI withdrawal	Up to Week 96
Number of Participants With Adverse Events (AE)	Treatment-emergent adverse events (TEAEs) were summarized for each cohort	Up to Week 96
Number of Participants With Serious Adverse Events (SAE)	Serious adverse events (SAEs) were summarized for each cohort	Up to Week 96
Number of Participants With Abnormalities in Clinical Laboratory Tests	Treatment-emergent laboratory abnormalities of at least grade 3 are summarized for each cohort	Up to Week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Meeting the NRTI Withdrawal Criteria at Week 44	Percentage of participants meeting the NRTI withdrawal criteria at Week 44 was summarized for each cohort	Week 44
Percentage of Participants With HBsAg Loss With or Without Antibodies to Hepatitis B Surface Antigen (Anti-HBs) at Week 72	Percentage of participants with HBsAg loss with or without antibodies to hepatitis B surface antigen (anti-HBs) at Week 72 was summarized for each cohort	Week 72
Percentage of Participants With HBsAg Loss at Any Timepoint	Percentage of participants with HBsAg loss at any timepoint was summarized for each cohort	Up to Week 72
Percentage of Participants With HBsAg Seroconversion at Any Timepoint	Percentage of participants with HBsAg seroconversion at any timepoint was summarized for each cohort	Up to Week 72
Change From Baseline in Serum HBsAg at Week 72	Change from baseline in serum HBsAg at Week 72 was summarized for each cohort	Week 72
Percentage of Participants With HBeAg Loss and/or Anti-HBe Seroconversion at Week 44 in Those Who Were HBeAg Positive at Screening	Percentage of participants with HBeAg loss and/or anti-HBe seroconversion at Week 44 in those who were HBeAg positive at screening was summarized for each cohort	Week 44
Change From Baseline in Serum Appearance and/or Titer of Anti-HBs at Any Timepoint	Change from baseline in serum appearance and/or titer of anti-HBs at any timepoint was summarized for each cohort	Up to Week 72

Collaborators and Investigators

• Sponsor: Brii Biosciences Limited
• Collaborators: VBI Vaccines Inc.; Vir Biotechnology, Inc.
• Investigators: Study Director: Xiaofei Chen, Brii Biosciences Limited

Publications and helpful links

General Publications

• Ji Y, Le Bert N, Lai-Hung Wong G, Douglas MW, Lee A, Zhu C, Wang B, Lv J, Li D, Tan Y, Ma H, Chen J, Chen X, Zhu Q, Yuen MF, Bertoletti A. The Impact of Hepatitis B Surface Antigen Reduction via Small Interfering RNA Treatment on Natural and Vaccine (BRII-179)-Induced Hepatitis B Virus-Specific Humoral and Cellular Immune Responses. Gastroenterology. 2025 Jul;169(1):136-149. doi: 10.1053/j.gastro.2025.02.016. Epub 2025 Mar 3.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2021
• Primary Completion (Actual): July 4, 2023
• Study Completion (Actual): July 4, 2023

Study Registration Dates

• First Submitted: February 7, 2021
• First Submitted That Met QC Criteria: February 7, 2021
• First Posted (Actual): February 11, 2021

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Hepatitis; HBV; Chronic Hepatitis B; Hepatitis B Virus
• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Pathological Conditions, Signs and Symptoms; Hepatitis; Hepatitis B; Hepatitis B, Chronic
• Other Study ID Numbers: BRII-179-835-001

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