A Study to Evaluate the Efficacy and Safety of Combination Therapy of BRII-179, BRII-835 and PEG-IFNα in Participants With Chronic Hepatitis B Virus (HBV) Infection (ENHANCE)

A Phase 2 Multicenter, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Combination Therapy of BRII-179, BRII-835 and Pegylated Interferon Alpha (PEG-IFNα) in Participants With Chronic Hepatitis B Virus (HBV) Infection (ENHANCE)

This Phase 2, randomized, double-blind study will evaluate the clinical efficacy and safety of the combination therapy of BRII-179, BRII-835, plus PEG-IFNα compared to PEG-IFNα in adult participants with chronic HBV infection without cirrhosis receiving neucloes(t)ide reverse transcriptase inhibitors (NRTIs) as background therapy.

Study Overview

• Status: Recruiting
• Conditions: Chronic Hepatitis B Virus (HBV) Infection
• Intervention / Treatment: Biological: PEG-IFNα; Biological: BRII-179; Drug: BRII-835 (VIR-2218); Drug: Placebo of BRII-179; Drug: Placebo of BRII-835

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Research, Brii Biosciences; Phone Number: +86 10 6299 8808; Email: clinicaltrials@briibio.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Investigative Site 86001
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Investigative Site 86003
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Investigative Site 86004
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Investigative Site 86005
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Investigative Site 86016
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Investigative Site 86002
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Investigative Site 86013
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Investigative Site 86015
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Investigative Site 86006
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Investigative Site 86007
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • Investigative Site 86010
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • Investigative Site 86011
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • Investigative Site 86012
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Investigative Site 86009

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female aged 18-60 years.
• Body mass index ≥ 18 kg/m2 and ≤ 32 kg/m2.
• Chronic HBV infection for ≥ 6 months.
• On NRTI therapy with HBV DNA < LLOQ for ≥ 6 months.
• Serum ALT and AST ≤ ULN at screening visit.

Exclusion Criteria:

• Any clinically significant chronic medical conditions other than chronic HBV infection that makes the participant unsuitable for participation in the study.
• Significant liver fibrosis or cirrhosis.
• History of clinically significant chronic liver disease from any cause other than chronic HBV infection.
• History of hepatic decompensation.
• Diagnosed or suspected hepatocellular carcinoma.
• Current or past history of infection with HIV, HCV or HDV.
• Any laboratory test abnormality that may contradict treatment with PEG-IFNα.
• Known history of immunological function impairment.
• History of intolerance to intramuscular or subcutaneous injection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo of BRII-179 + Placebo of BRII-835 + PEG-IFNα; Participants will receive placebo of BRII-179, placebo of BRII-835 and PEG-IFNα.	Biological: PEG-IFNα; PEG-IFNα will be given via subcutaneous injection; Other Names: Pegylated interferon alfa; Drug: Placebo of BRII-179; Placebo of BRII-179 will be given via intramuscular injection; Drug: Placebo of BRII-835; Placebo of BRII-835 will be given via subcutaneous injection
Experimental: Regimen 1: BRII-179 + BRII-835 + PEG-IFNα; Participants will receive BRII-179, BRII-835 and PEG-IFNα as a combination therapy (Regimen 1).	Biological: PEG-IFNα; PEG-IFNα will be given via subcutaneous injection; Other Names: Pegylated interferon alfa; Biological: BRII-179; BRII-179 will be given via intramuscular injection; Drug: BRII-835 (VIR-2218); BRII-835 will be given via subcutaneous injection; Other Names: elebsiran
Experimental: Regimen 2: BRII-179 + BRII-835 + PEG-IFNα; Participants will receive BRII-179, BRII-835 and PEG-IFNα as a combination therapy (Regimen 2).	Biological: PEG-IFNα; PEG-IFNα will be given via subcutaneous injection; Other Names: Pegylated interferon alfa; Biological: BRII-179; BRII-179 will be given via intramuscular injection; Drug: BRII-835 (VIR-2218); BRII-835 will be given via subcutaneous injection; Other Names: elebsiran

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage of participants achieving HBsAg seroclearance.	Up to 48 weeks
Percentage of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).	Up to 96 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants achieving HBsAg seroconversion.	Up to 48 weeks
Percentage of participants achieving HBsAg seroclearance.	Up to 72 weeks
Percentage of participants achieving HBsAg seroconversion.	Up to 72 weeks
Percentage of participants achieving functional cure.	Up to 96 weeks

Collaborators and Investigators

• Sponsor: Brii Biosciences Limited
• Investigators: Study Director: Xiaofei Chen, Brii Biosciences Limited

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: October 12, 2024
• First Submitted That Met QC Criteria: October 17, 2024
• First Posted (Actual): October 21, 2024

Study Record Updates

• Last Update Posted (Actual): May 23, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis A; Hepatitis; Infections; Communicable Diseases; Hepatitis B; Hepatitis B, Chronic; Hepatitis, Chronic; Anti-Infective Agents; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antiviral Agents; Interferons; Interferon-alpha
• Other Study ID Numbers: BRII-179-835-003

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