Actively Recruiting

Phase 2
Age: 18Years - 70Years
All Genders
NCT05771402

A Novel Combination Therapeutic Strategy Aiming to Functional Cure for Chronic Hepatitis B Virus Infection (Sustained HBsAg Loss) (B)

Led by The Second Affiliated Hospital of Chongqing Medical University · Updated on 2025-09-11

120

Participants Needed

1

Research Sites

168 weeks

Total Duration

On this page

Sponsors

T

The Second Affiliated Hospital of Chongqing Medical University

Lead Sponsor

T

The Affiliated Hospital Of Southwest Medical University

Collaborating Sponsor

AI-Summary

What this Trial Is About

Hepatitis B virus (HBV) infection is a major public health threat in China. At present, a functional cure, also known as clinical cure or sustained Hepatitis B surface antigen (HBsAg) loss, is recommended as the ideal endpoint of HBV treatment. However, HBsAg loss can be achieved in less than 10% of chronic hepatitis B (CHB) patients treated with current available antiviral drug interferon (IFNα) or nucleos(t)ide analogues (NAs) monotherapy. With the support of the national major special funding for infectious diseases from "11th Five-Year Plan" to "13th Five-Year Plan", we have implemented a pioneer clinical study of sequential combination of IFNα therapy on NAs to treat NAs-treated CHB patients (ie. New Switch Study). This is the world's first clinical trial aiming to functional cure, which increased the rate of HBsAg loss to 15% in the overall population in our study, and to 30-50% among those with lower baseline HBsAg levels. How to further improve the HBsAg loss rate is an urgent issue for us. The key point of achieving functional cure is to reverse the HBV-specific T cell exhaustion and establish the long-term immune control against HBV infection. (Programmed death-1) PD-1/programmed death-ligand 1 (PD-L1) axis blockade has been demonstrated to reinvigorate exhausted CD8+ T cells, and would be a potential strategy to treat chronic HBV infection. In this study, a large multicenter prospective study will be performed to explore the safety and efficacy of a novel combination strategy involving immune checkpoint inhibitor (anti-PD-1 antibody) and IFNα in CHB patients, observe the HBsAg loss rate in NA-treated CHB patients receiving this combination strategy, evaluate the potential of breaking immune tolerance by this strategy, and further assess its efficacy to further improve the clinical cure rate on the basis of New Switch Study. Based on New Switch Study, this study further attempts to reverse T cell exhaustion in CHB patients, explore a novel platform of combination therapy development for clinical cure, and ultimately increase the HBsAg loss rate to higher than 50% in overall patients. The implementation of the project is expected to reduce the burden of HBV infection in China and contribute to the goal of global elimination of hepatitis B and C by 2030 (WHO 2030).

CONDITIONS

Official Title

A Novel Combination Therapeutic Strategy Aiming to Functional Cure for Chronic Hepatitis B Virus Infection (Sustained HBsAg Loss) (B)

Who Can Participate

Age: 18Years - 70Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Signed informed consent and able to complete the study as required
  • Willingness to use effective contraception from inclusion to 30 days after last treatment if male or female of childbearing age
  • Age 18 to 70 years
  • Male weight at least 45 kg; female weight at least 40 kg; BMI between 18 and 32 kg/m�b2
  • Chronic Hepatitis B patients treated or untreated with nucleos(t)ide analogues (NAs)
Not Eligible

You will not qualify if you...

  • History or suspicion of allergy to study drug or its components
  • Use of CYP3A4 inhibitors, inducers, or substrates within 28 days before enrollment
  • Use of immunosuppressants, immunomodulators, or cytotoxic drugs within 6 months before enrollment, or live attenuated vaccine within 1 month before enrollment
  • Acute infection requiring intravenous antibiotics within 2 weeks before enrollment or ongoing infection needing treatment
  • Significant liver disease not caused by HBV
  • Decompensated cirrhosis or progressive liver fibrosis
  • Primary liver cancer or recent history of other cancers
  • History of pathological fracture or osteoporosis
  • Gastrointestinal disorders affecting drug absorption or persistent severe gastrointestinal symptoms
  • Serious diseases of circulatory, respiratory, urinary, blood, metabolic, immune, mental, neurological, renal, or other systems
  • Major trauma or surgery within 3 months before enrollment or planned surgery during study
  • Recent significant blood donation, blood loss, or transfusion
  • Low platelet, white blood cell, or neutrophil counts; high bilirubin; low albumin; reduced kidney function; abnormal coagulation
  • Positive for hepatitis C, HIV, or syphilis tests
  • History of continuous alcohol abuse in past 3 years
  • History of drug dependence or abuse in past year
  • Participation in other clinical trials with investigational drugs or devices within past 3 months
  • Pregnant or breastfeeding women
  • Other factors deemed unsuitable by researchers

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Trial Site Locations

Total: 1 location

1

The 2nd affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China, 400010

Actively Recruiting

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Research Team

D

Dachuan Cai, MD

CONTACT

M

Min Chen, PhD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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