HZBio1在中国健康受试者中的安全性、耐受性、药代动力学、药效学和免疫原性：一项随机1a期研究
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of HZBio1 in Chinese Healthy Subjects: A Randomized Phase 1a Study
聚乙二醇修饰的重组尿酸酶是治疗高尿酸血症和痛风的指南推荐方案之一，HZBio1是其中一种新候选药。这项首次人体、单次递增剂量1a期试验在中国健康受试者中评估其安全性、耐受性、药代动力学、药效学和免疫原性。30名受试者分入5个HZBio1剂量组，10人接受安慰剂，单次肌内注射0.96至12毫克。35天随访中所有不良事件均为1级或2级，HZBio1组与安慰剂组的不良事件发生率分别为76.7%对60.0%。血尿酸在单次给药后下降，144至192小时达最低点，9至12毫克组降幅最明显。受试者产生了低滴度抗聚乙二醇抗体，几乎未检出抗药抗体，也没有中和抗体。作者认为3至12毫克剂量耐受良好，降尿酸效果有前景。
为什么推荐给您：新候选聚乙二醇化尿酸酶的首次人体试验，显示耐受良好并有降尿酸活性，属早期阳性进展。
不需要生物学背景，多打比方
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摘要Abstract
INTRODUCTION: Polyethylene glycol-modified (PEGylated) recombinant uricase is a promising guideline-recommended treatment for hyperuricemia and gout. This first-in-human, single ascending dose, phase 1a trial evaluated the tolerability, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of HZBio1 in Chinese healthy subjects.
METHODS: The present study enrolled healthy subjects (aged 18-45 years) between March 8, 2021 and January 14, 2022. Thirty subjects were randomly assigned into 5 HZBio1 cohorts (6 per dose cohort) following the dose escalation scheme, and 10 received placebo. Each subject received a single dose of HZBio1 (in the range 0.96-12 mg) or placebo, by intramuscular injection.
RESULTS: All treatment-emergent adverse events (TEAEs) were grade 1 or 2 in severity during a 35-day follow-up period. The TEAEs and drug-related TEAEs incidences were 76.7% versus 60.0% and 73.3% versus 60.0% in the HZBio1 and placebo cohorts, respectively. HZBio1 exposure increased in a greater than dose-proportional manner following single-dose administration across the 3- to 12-mg range. Plasma uric acid levels decreased following a single dose of HZBio1 and reached the nadir at 144-192 h. The reduction in uric acid concentration was most pronounced in the 9- to 12 mg HZBio1 cohorts. HZBio1 administration elicited low-titer anti-PEG (IgG, IgM) antibodies, whereas antidrug antibodies were rarely detected, and no subjects developed neutralizing antibodies.
CONCLUSION: HZBio1 at doses of 3-12 mg was well tolerated in healthy subjects, had an acceptable pharmacokinetics profile, and promising urate-lowering effect.
TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04765995.