Hepatitis B, ChronicPhase 2NCT04749368

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 study testing BRII-835 (VIR-2218), BRII-179 (VBI-2601) with IFN-α and BRII-179 (VBI-2601) in people with Hepatitis B, Chronic, run by Brii Biosciences Limited at 28 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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 Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Hepatitis B, Chronic
What is being tested?: BRII-835 (VIR-2218), BRII-179 (VBI-2601) with IFN-α and BRII-179 (VBI-2601)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 91 participants
Where: 28 sitesin 6 countries
Study dates: 12 Apr 2021to 4 Jul 2023
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

28 sites in 6 countries.

Country

City, postcode or hospital

28 sites in 6 countries

China9 sites

Investigative Site 88602
Changhua, Taiwan, 500
Investigative Site 85201
Hong Kong
Investigative Site 85202
Hong Kong
Investigative Site 85203
Hong Kong
Investigative Site 88601
Kaohsiung, Taiwan, 83301
Investigative Site 88604
Kaohsiung, Taiwan
Investigative Site 85204
NEW Territories, Hong Kong
Investigative Site 88603
Taichung, Taiwan, 40447
Investigative Site 88605
Taipei CITY, 10048

Other trials in China

Thailand7 sites

Investigative Site 66001
Bangkok, 10330
Investigative Site 66003
Chiang Mai, 50200
Investigative Site 66002
Khon Kaen, 40002
Investigative Site 66005
Nonthaburi, 11000
Investigative Site 66006
Nonthaburi, 11000
Investigative Site 66004
Pathum Thani, 12120
Investigative Site 66007
Songkhla, 90110

Other trials in Thailand

South Korea5 sites

Investigative Site 82004
Busan, 49241
Investigative Site 82003
Seongnam-si, Gyeonggi-do, 13496
Investigative Site 82001
Seoul, 3080
Investigative Site 82005
Seoul, 3722
Investigative Site 82002
Seoul, 5505

Other trials in South Korea

Australia3 sites

Investigative Site 61004
Herston, Queensland, 4029
Investigative Site 61002
Kingswood, New South Wales, 2747
Investigative Site 61001
Westmead, New South Wales, 2145

Other trials in Australia

New Zealand2 sites

Investigative Site 64001
Auckland, 2025
Investigative Site 64002
Dunedin Central, Dunedin, 9016

Other trials in New Zealand

Singapore2 sites

Investigative Site 65001
Singapore, 169608
Investigative Site 65002
Singapore, 529889

Other trials in Singapore

About this study

Official title: 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

Conditions: Hepatitis B, Chronic
Being tested: BRII-835 (VIR-2218), BRII-179 (VBI-2601) with IFN-α, BRII-179 (VBI-2601)
Keywords: Hepatitis B Virus, Chronic Hepatitis B, HBV, Hepatitis
Medical subject headings: Hepatitis B, Chronic, Hepatitis B, Hepatitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BRII-835 (VIR-2218)Drug
BRII-835 (VIR-2218) will be given by subcutaneous injection
BRII-179 (VBI-2601) with IFN-αBiological
BRII-179 (VBI-2601) with IFN-α will be co-administered by intramuscular injection
BRII-179 (VBI-2601)Biological
BRII-179 (VBI-2601) will be administered by intramuscular injection

Study groups in NCT04749368
Study group	Role	What they receive
Cohort A	Experimental	Participants will receive BRII-835 (VIR-2218) for 32 weeks Receives: Drug: BRII-835 (VIR-2218)
Cohort B	Experimental	Participants will receive BRII-835 (VIR-2218) and BRII-179 (VBI-2601) with IFN-α up to Week 40 Receives: Drug: BRII-835 (VIR-2218); Biological: BRII-179 (VBI-2601) with IFN-α
Cohort C	Experimental	Participant will receive BRII-835 (VIR-2218) and BRII-179 (VBI-2601) up to Week 40 Receives: Drug: BRII-835 (VIR-2218); Biological: BRII-179 (VBI-2601)

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: Up to Week 96
Number of Participants With Adverse Events (AE)
Treatment-emergent adverse events (TEAEs) were summarized for each cohort
Measured: Up to Week 96
Number of Participants With Serious Adverse Events (SAE)
Serious adverse events (SAEs) were summarized for each cohort
Measured: 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
Measured: Up to Week 96

Secondary outcomes (7)

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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Up to Week 72

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Apr 20214 Jul 2023

First posted11 Feb 2021
Study start12 Apr 2021
Primary completion4 Jul 2023
Study completion4 Jul 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 91 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04749368
Sponsor's protocol ID: BRII-179-835-001
Status last verified: Jun 2026
First submitted: 7 Feb 2021
Last updated: 23 Jul 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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.
PubMed 40043858

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B

All Hepatitis B, Chronic trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT04749368
Acronym / sponsor ID: BRII-179-835-001
Conditions: Hepatitis B, Chronic
Keywords: Hepatitis B Virus, Chronic Hepatitis B, HBV, Hepatitis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 91 participants (actual)
Lead sponsor: Brii Biosciences LimitedIndustry (pharma, biotech, devices)
Collaborators: Vir Biotechnology, Inc., VBI Vaccines Inc.
Study start: 12 Apr 2021 (actual)
Primary completion: 4 Jul 2023 (actual)
Study completion: 4 Jul 2023 (actual)
First posted: 11 Feb 2021 (actual)
Results: Posted 23 Jul 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Cohort A	Experimental	Drug: BRII-835 (VIR-2218)Participants will receive BRII-835 (VIR-2218) for 32 weeks
Cohort B	Experimental	Drug: BRII-835 (VIR-2218), Biological: BRII-179 (VBI-2601) with IFN-αParticipants will receive BRII-835 (VIR-2218) and BRII-179 (VBI-2601) with IFN-α up to Week 40
Cohort C	Experimental	Drug: BRII-835 (VIR-2218), Biological: BRII-179 (VBI-2601)Participant will receive BRII-835 (VIR-2218) and BRII-179 (VBI-2601) up to Week 40

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BRII-835 (VIR-2218)BRII-835 (VIR-2218) will be given by subcutaneous injection	Drug	Cohort A, Cohort B, Cohort C
BRII-179 (VBI-2601) with IFN-αBRII-179 (VBI-2601) with IFN-α will be co-administered by intramuscular injection	Biological	Cohort B
BRII-179 (VBI-2601)BRII-179 (VBI-2601) will be administered by intramuscular injection	Biological	Cohort C

Primary outcome

Percentage of Participants With Sustained HBsAg Loss During the 48-week Follow-up Period After NRTI Withdrawal
Time frame: Up to Week 96
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
Number of Participants With Adverse Events (AE)
Time frame: Up to Week 96
Treatment-emergent adverse events (TEAEs) were summarized for each cohort
Number of Participants With Serious Adverse Events (SAE)
Time frame: Up to Week 96
Serious adverse events (SAEs) were summarized for each cohort
Number of Participants With Abnormalities in Clinical Laboratory Tests
Time frame: Up to Week 96
Treatment-emergent laboratory abnormalities of at least grade 3 are summarized for each cohort

7 secondary outcomes

Percentage of Participants Meeting the NRTI Withdrawal Criteria at Week 44
Time frame: Week 44
Percentage of Participants With HBsAg Loss With or Without Antibodies to Hepatitis B Surface Antigen (Anti-HBs) at Week 72
Time frame: Week 72
Percentage of Participants With HBsAg Loss at Any Timepoint
Time frame: Up to Week 72
Percentage of Participants With HBsAg Seroconversion at Any Timepoint
Time frame: Up to Week 72
Change From Baseline in Serum HBsAg at Week 72
Time frame: Week 72
Percentage of Participants With HBeAg Loss and/or Anti-HBe Seroconversion at Week 44 in Those Who Were HBeAg Positive at Screening
Time frame: Week 44
Change From Baseline in Serum Appearance and/or Titer of Anti-HBs at Any Timepoint
Time frame: Up to Week 72

Results and safety

Results posted to the registry on 23 Jul 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort A	11	10
Cohort B	39	37
Cohort C	41	40

Primary outcome: Percentage of Participants With Sustained HBsAg Loss During the 48-week Follow-up Period After NRTI Withdrawal

Time frame: Up to Week 96. Count of participants. Unit: Participants

Measure	Cohort A n = 10	Cohort B n = 39	Cohort C n = 41
Value	0	0	0

Population analysed: Full analysis set included all participants who were randomized and had received at least 1 dose of study treatment with evaluable measurements of antiviral activity and immunological markers

Primary outcome: Number of Participants With Adverse Events (AE)

Time frame: Up to Week 96. Count of participants. Unit: Participants

Measure	Cohort A n = 10	Cohort B n = 39	Cohort C n = 41
Value	10	37	37

Population analysed: Safety analysis set included all participants who were randomly assigned and received at least 1 dose of study treatment

Primary outcome: Number of Participants With Serious Adverse Events (SAE)

Time frame: Up to Week 96. Count of participants. Unit: Participants

Measure	Cohort A n = 10	Cohort B n = 39	Cohort C n = 41
Value	0	3	6

Population analysed: Safety analysis set included all participants who were randomly assigned and received at least 1 dose of study treatment

Primary outcome: Number of Participants With Abnormalities in Clinical Laboratory Tests

Time frame: Up to Week 96. Count of participants. Unit: Participants

Measure	Cohort A n = 10	Cohort B n = 39	Cohort C n = 41
>= grade 3 hematology abnormalities	1	1	1
>= grade 3 lymphocytes decreased	1	1	1
>= grade 3 coagulation abnormalities	0	0	0
>= grade 3 chemistry abnormalities	0	2	2
>= grade 3 creatine kinase increased	0	2	2

Population analysed: Safety analysis set included all participants who were randomly assigned and received at least 1 dose of study treatment

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 96 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort A	0 of 10 (0%)	10 of 10 (100%)	0 of 10
Cohort B	3 of 39 (7.7%)	37 of 39 (94.9%)	0 of 39
Cohort C	6 of 41 (14.6%)	37 of 41 (90.2%)	0 of 41

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40043858Ji 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.
Individual participant dataSharing planned: No

Related trials for Hepatitis B, Chronic

Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
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Hepatitis B
Enrolling by invitationPhase 1
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Chronic Hepatitis B

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Xiaofei Chen study director

Brii Biosciences Limited

28 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BRII-835 (VIR-2218), BRII-179 (VBI-2601) with IFN-α and BRII-179 (VBI-2601) in people with Hepatitis B, Chronic, run by Brii Biosciences Limited at 28 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in China, Thailand, South Korea, Australia, New Zealand and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Sustained HBsAg Loss During the 48-week Follow-up Period After NRTI Withdrawal (time frame: Up to Week 96). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04749368, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2026.