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Updated: Sep 26, 2026
High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)
Published on: May 10, 2016
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of HZBio1 in Chinese Healthy Subjects: A
Hongzhong Liu1, Xin Zheng1, Chuanqing Yang1
1Clinical Pharmacology Research Center, Beijing Key Laboratory of Key Technologies for Early Clinical Trial Evaluation of Innovative Drugs for Major Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
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.
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