Randomized, Double-Blind, Placebo-Controlled, Phase I, Dose- Escalation Study to Evaluate the Tolerance, Pharmacokinetics, Pharmacodynamics and Immunogenicity of PEGylated Urate Oxidase for Injection in Healthy Adults and Hyperuricemia Volunteers: Study Protocol

Introduction: Hyperuricemia is a disease with abnormal purine metabolism, which leads to the increase of urate concentration. It is an independent risk factor for the occurrence and development of metabolic syndrome, type 2 diabetes, hypertension, cardiovascular disease, chronic kidney disease, and gout. The enzyme urate oxidase can metabolize urate to allantoin, resulting in decreased urate concentrations. Pegylated the urate oxidase can extend half-life and decrease immunogenicity of the protein. This trial aims to evaluate the safety, tolerability, pharmacokinetics(PK), pharmacodynamics(PD) and immunogenicity of a new intravenous PEGylated urate oxidase produced by Xiuzheng Bio-Medicine Research Institute Co., Ltd. Methods and Analysis: A randomized, double-blind, placebo-controlled, phase I, dose escalation study will be conducted in China. In total, 56 subjects will be enrolled in the study, with 24 healthy subjects in the low dose-escalation stage and 32 patients with hyperuricemia in the high dose-escalation stage. There is a bridging between the two stages. Subjects are randomized to PEGylated urate oxidase or the placebo in a 3:1 ratio in each group and followed up for 71 days observation. The primary outcomes include PK, PD, tolerability; the secondary outcomes include safety and immunogenicity. Ethics and Dissemination: The trial is performed abiding by the Declaration of Helsinki, Good clinical practice (GCP) and the guidelines of China National Medical Products Administration (NMPA). Relevant documents, including protocol, informed consent and drug inspection report, are all approved independently by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University. The first subject was enrolled on January 17, 2022. Trial Registration: Clinicaltrials, NCT05226013 (Registered April 2, 2022, Retrospectively registered). ChinaDrugTrials, CTR20211801(Registered July 27, 2021). Keywords: PEGylated urate oxidase, healthy volunteers, patients with hyperuricemia, study protocol