{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:57:40Z","timestamp":1785326260885,"version":"3.55.0"},"reference-count":27,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Denosumab is a human IgG2 monoclonal antibody against receptor activator of nuclear factor kappa\u2010B ligand (RANKL) for the treatment of osteoporosis and bone loss. HLX14 is a proposed biosimilar of denosumab. This randomized, parallel\u2010group, two\u2010part, phase I study aimed to compare the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 with reference denosumab in Chinese healthy adult male participants. In Part 1, participants were randomized 1:1 and given HLX14 or reference denosumab sourced from the European Union (EU). In double\u2010blind Part 2, participants were randomized 1:1:1:1 to receive HLX14 or denosumab sourced from the United States, EU, or China. All study drugs were administered via subcutaneous injection at a single dose of 60\u2009mg. The primary endpoints were area under the serum drug concentration\u2013time curve from time 0 to the last concentration\u2010quantifiable time <jats:italic>t<\/jats:italic> (AUC<jats:sub>0\u2013t<\/jats:sub>), maximum serum drug concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>), and area under the serum drug concentration\u2013time curve from time 0 to infinity (AUC<jats:sub>0\u2013inf<\/jats:sub>). Twenty\u2010four participants were randomized in Part 1 and 228 in Part 2. The 90% confidence intervals of geometric mean ratio of AUC<jats:sub>0\u2013<jats:italic>t<\/jats:italic><\/jats:sub>, <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, and AUC<jats:sub>0\u2013inf<\/jats:sub> between HLX14 and denosumab from different sources fell within the pre\u2010specified similarity margins of 0.80\u20131.25 (AUC<jats:sub>0\u2013<jats:italic>t<\/jats:italic><\/jats:sub>, 0.91\u20131.13; <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, 0.91\u20131.13; AUC<jats:sub>0\u2013inf<\/jats:sub>, 0.91\u20131.12), demonstrating pharmacokinetic similarity. No notable difference was observed among treatment groups in pharmacodynamics, safety, or immunogenicity. HLX14 demonstrated highly similar pharmacokinetic characteristics with comparable pharmacodynamics, safety, and immunogenicity to denosumab, supporting its further investigation as a potential denosumab biosimilar.<\/jats:p>","DOI":"10.1111\/cts.70089","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T17:40:11Z","timestamp":1734630011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of <scp>HLX14<\/scp> versus reference denosumab in healthy males: A randomized phase I study"],"prefix":"10.1111","volume":"17","author":[{"given":"Nanyang","family":"Li","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Research Center, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Chu","sequence":"additional","affiliation":[{"name":"Phase I Clinical Research Center The Affiliated Wuxi People's Hospital of Nanjing Medical University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Phase I Clinical Research Center Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Wu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Research Center, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Wei","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Research Center, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Henlius Biotech, Inc.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhui","family":"Hu","sequence":"additional","affiliation":[{"name":"Shanghai Henlius Biotech, Inc.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Yu","sequence":"additional","affiliation":[{"name":"Shanghai Henlius Biotech, Inc.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Henlius Biotech, Inc.  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6072-118X","authenticated-orcid":false,"given":"Wei'an","family":"Yuan","sequence":"additional","affiliation":[{"name":"Phase I Clinical Research Center Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Huang","sequence":"additional","affiliation":[{"name":"Phase I Clinical Research Center The Affiliated Wuxi People's Hospital of Nanjing Medical University  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Research Center, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"National Institute of Arthritis and Musculoskeletal and Skin Diseases.Osteoporosis. Reviewed December 2022.https:\/\/www.niams.nih.gov\/health\u2010topics\/osteoporosis. Accessed February 28 2024.https:\/\/www.niams.nih.gov\/health\u2010topics\/osteoporosis"},{"key":"e_1_2_13_3_1","unstructured":"MSD MANUAL Professional Version.Osteoporosis. Reviewed\/Revised September 2023.https:\/\/www.msdmanuals.com\/professional\/musculoskeletal\u2010and\u2010connective\u2010tissue\u2010disorders\/osteoporosis\/osteoporosis?query=osteoporosis. Accessed February 28 2024."},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-022-06454-3"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.12114\/j.issn.1007-9572.2023.0121"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-021-05900-y"},{"key":"e_1_2_13_7_1","unstructured":"National Osteoporosis Guideline Group UK.Clinical guideline for the prevention and treatment of osteoporosis. Updated September 2021.https:\/\/www.nogg.org.uk\/full\u2010guideline. Accessed February 28 2024."},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-02236"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02646-5"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1005681"},{"key":"e_1_2_13_11_1","unstructured":"Prolia(R) (Denosumab) Granted Marketing Authorization in the European Union.2010.https:\/\/www.amgen.com\/newsroom\/press\u2010releases\/2010\/05\/proliar\u2010denosumab\u2010granted\u2010marketing\u2010authorization\u2010in\u2010the\u2010european\u2010union. Accessed March 12 2024."},{"key":"e_1_2_13_12_1","unstructured":"FDA Approves Amgen's Prolia(TM) (Denosumab) for Treatment of Postmenopausal Women With Osteoporosis at High Risk for Fracture.2010.https:\/\/www.amgen.com\/newsroom\/press\u2010releases\/2010\/06\/fda\u2010approves\u2010amgens\u2010proliatm\u2010denosumab\u2010for\u2010treatment\u2010of\u2010postmenopausal\u2010women\u2010with\u2010osteoporosis\u2010at\u2010high\u2010risk\u2010for\u2010fracture. Accessed March 12 2024."},{"key":"e_1_2_13_13_1","unstructured":"Amgen Receives National Medical Products Administration Approval For Prolia\u00ae (Denosumab) in China.2020.https:\/\/www.amgen.cn\/en\/media\/amgen_denosumab_china.html. Accessed March 12 2024."},{"key":"e_1_2_13_14_1","unstructured":"Prolia Summary of Product Characteristics. Latest renewal on January 16 2020.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/prolia\u2010epar\u2010product\u2010information_en.pdf. Accessed March 12 2024."},{"key":"e_1_2_13_15_1","unstructured":"Prolia\u00ae Prescribing Information.Recent major changes in March 2024.https:\/\/www.pi.amgen.com\/united_states\/prolia\/prolia_pi.pdf. Accessed March 12 2024."},{"key":"e_1_2_13_16_1","unstructured":"Amgen Prolia\u00ae Receives Approval for New Indication for the Treatment of Osteoporosis in Men at High Risk for Fracture.2023.https:\/\/www.amgen.cn\/cn\/media\/amgen_Prolia.html. Accessed March 12 2024."},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2521"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2016.06.036"},{"key":"e_1_2_13_19_1","unstructured":"Sandoz receives FDA approval for first and only denosumab biosimilars.2024.https:\/\/www.sandoz.com\/sandoz\u2010receives\u2010fda\u2010approval\u2010first\u2010and\u2010only\u2010denosumab\u2010biosimilars\/. Accessed March 12 2024."},{"key":"e_1_2_13_20_1","unstructured":"China's First Denosumab Biosimilar Boyoubei\u00ae Approved for Launch by NMPA.2022.https:\/\/www.boan\u2010bio.com\/en\/info.php?id=164. Accessed March 13 2024."},{"key":"e_1_2_13_21_1","unstructured":"The World's Second Approved Biosimilars of Denosumab (MAILISHU).2023.https:\/\/www.mabwell.com\/en\/news_info\/id\u201098.html. Accessed March 13 2024."},{"key":"e_1_2_13_22_1","unstructured":"Qilu Pharmaceutical's Denosumab Injection (LUKEXIN) Approved for Marketing.2023.https:\/\/www.qilu\u2010pharma.com\/news_details\/157.html. Accessed March 13 2024."},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2022.06.007"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2023.2178298"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/jbmr\/zjae016"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-022-00954-y"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2017.21"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0197984"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70089","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T15:36:28Z","timestamp":1735054588000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":27,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/cts.70089"],"URL":"https:\/\/doi.org\/10.1111\/cts.70089","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"2024-09-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70089"}}