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Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of HZBio1 in Chinese Healthy Subjects: A Randomized Phase 1a Study

In brief

Single-dose HZBio1 lowered uric acid most at 9 to 12 mg

In 30 healthy Chinese adults, a single intramuscular dose of HZBio1 lowered plasma uric acid, with the strongest reduction at 9 to 12 mg and lowest levels reached after 6 to 8 days. Over 35 days, adverse events were all mild or moderate and occurred at similar rates to placebo; whether the urate-lowering effect benefits people with gout or remains safe with repeated dosing is unknown.

Journal
Advances in therapy (Q1)
Published
24 September 2026
Study design
Randomized controlled trial
Evidence level
Level 1, High (CEBM 1b)
Authors
Hongzhong Liu, Xin Zheng, Chuanqing Yang, Wei Tian, Ruijie Wan, Yu Wang, et al.
PMID
42782449
DOI
10.1007/s12325-026-03792-0

Why clinicians should know about it

  • Picked for Rheumatology (top studies of the week, 27 September 2026): High-quality evidence in a top journal

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.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.