Objective  To explore the situation and characteristics of clinical trials of 121 rare diseases in the Chinese First List of Rare Diseases over the past 10 years and to provide reference for promoting the researchand development of orphan drugs in China.

  Methods  The 121 rare diseases covered in the Chinese First List of Rare Diseases and Guidelines for Diagnosis and Treatment of Rare Diseases published in 2019 were retrieved as keywords on the National Medical Products Administration Registration and Information Disclosure Platform for Drug Clinical Studies (chinadrugtrials.org.cn) from November 1st, 2012 (Platform registration open time) to November 28th, 2021. The status and characteristics of rare disease clinical trials were analyzed from the perspectives of the number of registrations, geographical distribution, research fields, research design, and sample size.

  Results  A total of 235 clinical trials were collected, including 41 items of phase Ⅰ, 22 items of phase Ⅱ, 74 items of phase Ⅲ, 15 items of phase Ⅳ, 77 items of bioequivalence clinical trials, and 6 clinical trials. During the past 10 years, the number of rare diseases clinical trials in China showed an increasing trend, with an annual average growth rate of about 54%. A total of 16 kinds of rare diseases in the Chinese First List of Rare Diseases were involved in the early phase (phase Ⅰ and phase Ⅱ) clinical trials, mainly focusing on hemophilia, idiopathic pulmonary fibrosis, multiple sclerosis, and neuromyelitis optica. The researchers of rare disease clinical trials were mainly in big cities such as Beijing, Tianjin, and Shanghai. Phase Ⅰ clinical trials of rare diseases listed in the Chinese First List of Rare Diseases in China were mainly single-center(61%, 25/41) parallel controlled studies (46%, 19/41), Phase Ⅱ clinical trials were mainly multi-center parallel controlled studies (65%, 13/22), and phase Ⅲ clinical trials were mainly multi-center (99%, 73/74) single-arm trials (64%, 47/74). The sample size in clinical trials increased with the study stage. Phase Ⅰ clinical trials were mainly restricted to 11~50 cases (83%, 34/41), 59% (13/22) of phase Ⅱ clinical trials were more than 50 cases, and 53%(39/74) of phase Ⅲ clinical trials involved 51~500 cases.

  Conclusions  The research and development of orphan drugs in China is still at an early stage, covering few rare diseases in the Chinese First List of Rare Diseases, but it has shown a rapidly growing trend in recent years. At present, the development of rare disease drugs is still based on traditional clinical trial design. It is therefore necessary to explore more new clinical research strategies according to the disease and drug mechanism to promote the development of rare disease drugs.