A Novel Combination Therapeutic Strategy for Functional Cure of Chronic Hepatitis B Virus Infection (B)
Status:
Not yet recruiting
Trial end date:
2023-12-31
Target enrollment:
Participant gender:
Summary
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).
Phase:
Phase 4
Details
Lead Sponsor:
The Second Affiliated Hospital of Chongqing Medical University
Collaborators:
Guizhou Provincial People's Hospital The Affiliated Hospital Of Southwest Medical University