China bears a substantial disease burden of chronic hepatitis B （CHB）. Under current clinical management regimens for CHB， achieving functional cure （also termed clinical cure） is the core goal for the treatment of patients meeting treatment indications. To achieve the goal of functional cure， drug regulatory authorities in China and globally have successively issued technical criteria to provide guidance for the overall design and scientific evaluation of clinical trials for innovative drugs. However， the rapid development in scientific research， clinical practice， and new drug research and development in this field has brought new challenges， especially those concerning the assessment of the clinical value of investigational drugs. This article reviews the current status of clinical research and development of new drugs for achieving the functional cure of CHB worldwide， analyzes the characteristics of available clinical trial data， and focuses on key aspects of pivotal clinical trials for CHB functional cure drugs， including target populations （baseline HBsAg level）， HBsAg seroclearance response， HBsAg seroreversion after drug withdrawal， and clinically meaningful target threshold of functional cure response rate， in order to provide a reference for further refinement of related technical criteria.

Most patients with early stage chronic hepatitis B virus infection are in the immune-tolerant phase. Therefore, previously been generally believed that there is no disease progression or liver injury-related events, and poor antiviral efficacy in patients with immune-tolerant phase. With that in mind, antiviral therapy is generally not recommended in current domestic and foreign guidelines. However, more and more studies have shown that patients in the immune-tolerant phase may develop liver cirrhosis and hepatocellular carcinoma without treatment, so clinical treatment is urgently needed. Currently, drugs based on nucleocapsid inhibitor, immune modulation, and other novel mechanisms for viral replication are being developed to reduce hepatitis B surface antigen, which offers the possibility to achieve viral suppression or even functional cure in these patients. This paper mainly reviews and discusses the latest research progress, population characteristics, treatment needs, and design strategies of clinical trials of new drug for immune-tolerant phase population.

Allografts ; Anemia, Aplastic ; Haploidy ; Hematopoietic Stem Cell Transplantation ; Humans