{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:31:51Z","timestamp":1790303511762,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This Phase I trial aimed to evaluate the tolerability, pharmacokinetics, pharmacodynamics (PK\/PD), and immunogenicity of PEGylated uricase (PEG\u2010UOX) in healthy adults and patients with hyperuricaemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 48 subjects\u201424 healthy adults and 24 patients with hyperuricaemia\u2014were enrolled in a randomized, double\u2010blind, placebo\u2010controlled, dose\u2010escalation study. Participants received a single intravenous dose of PEG\u2010UOX ranging from 0.5 to 8\u2009mg. A sentinel dosing design was employed to allow for initial safety evaluation before dose escalation. Blood and urine samples were collected over a 21\u2010day follow\u2010up period to assess uric acid and allantoin levels. Safety was continuously monitored throughout the study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PEG\u2010UOX administration led to marked reductions in serum uric acid levels in both healthy and hyperuricaemic subjects, with the greatest efficacy observed in hyperuricaemic patients receiving the 8\u2009mg dose. Urinary excretion of uric acid decreased, while allantoin levels increased, confirming the uricolytic activity of PEG\u2010UOX. Immunogenicity analysis revealed a higher incidence of anti\u2010PEG antibodies in healthy subjects than in patients with hyperuricaemia, suggesting differential immune responses. No serious adverse events (SAEs) were reported; most treatment\u2010emergent adverse events were mild in severity, including transient, asymptomatic ST\u2010T changes and Ventricular Premature Contractions(VPCs) classified as mild (Grade 1) by independent cardiologists.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PEG\u2010UOX demonstrated favourable pharmacokinetics, urate\u2010lowering effects, and tolerability over a 21\u2010day observation period in both healthy adults and patients with hyperuricaemia. Its uricolytic mechanism offers a promising therapeutic alternative for managing hyperuricaemia, particularly in cases refractory to conventional urate\u2010lowering therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      Clinical trials, NCT05226013 (Registered 2 April 2022, retrospectively registered). ChinaDrugTrials (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.chinadrugtrials.org.cn\/\">www.chinadrugtrials.org.cn<\/jats:ext-link>\n                      ), CTR20211801 (registered 27 July 2021).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.16532","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T06:09:09Z","timestamp":1750831749000},"page":"4892-4902","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and safety of\n                    <scp>PEGylated<\/scp>\n                    uricase in healthy adults and patients with hyperuricaemia: A phase I, randomized, double\u2010blind, dose\u2010escalation, placebo\u2010controlled trial"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8161-536X","authenticated-orcid":false,"given":"Feifei","family":"Sun","sequence":"first","affiliation":[{"name":"The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xiuzheng Bio\u2010Medicine Research Institute Co. Ltd  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghai","family":"Yan","sequence":"additional","affiliation":[{"name":"Xiuzheng Bio\u2010Medicine Research Institute Co. Ltd  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Yu","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"He","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murong","family":"Liu","sequence":"additional","affiliation":[{"name":"Xiuzheng Bio\u2010Medicine Research Institute Co. Ltd  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binnan","family":"Huang","sequence":"additional","affiliation":[{"name":"Xiuzheng Bio\u2010Medicine Research Institute Co. 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