{"title":"一项随机、双盲、单剂量、平行组、两组研究，评估候选生物类似药AVT03 （70 mg/mL）在健康成年男性中的药代动力学相似性、安全性、耐受性和免疫原性。","authors":"Monika Tomaszewska-Kiecana, Felicitas Bullo, Lukasz Jaskiewicz, Serena Stamatakos, Hendrik Otto, Masna Rai, Abid Sattar, Steffen Leutz, Fausto Berti","doi":"10.1080/13543784.2025.2505469","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>This study (NCT05876949) compared the pharmacokinetic (PK) similarity, safety, and immunogenicity of AVT03, a candidate biosimilar, with reference product (RP) denosumab (Xgeva).</p><p><strong>Methods: </strong>Healthy male participants (<i>N</i> = 208, including 24 Japanese participants) were randomized 1:1 to receive one 120 mg dose of AVT03, or RP. PK similarity was demonstrated if the 90% confidence intervals (CI) for the ratio of geometric means for the primary PK parameters C<sub>max</sub> and AUC<sub>0-t</sub> were within 80.00% and 125.00%. Additional PK parameters included AUC<sub>0-inf</sub>, t<sub>max</sub>, K<sub>el</sub>, t<sub>1/2</sub>, V<sub>z</sub>/F, and CL/F. Safety and immunogenicity were also assessed.</p><p><strong>Results: </strong>The 90% CIs for the ratio of geometric means for the primary PK parameters were entirely contained within the prespecified margins of 80.00% and 125.00% (C<sub>max</sub> [98.26, 110.00]; AUC<sub>0-t</sub> [102.30, 113.60]), supporting demonstration of PK similarity. Consistency between Japanese participants and the overall population was shown. Safety and immunogenicity profiles were comparable between the two treatment arms.</p><p><strong>Conclusion: </strong>Results supported demonstration of PK similarity between AVT03 and RP. AVT03 had a safety and immunogenicity profile comparable to RP.</p><p><strong>Clinical trial registration: </strong>The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05876949); and 2022 -003,659-32 (EudraCT).</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-8"},"PeriodicalIF":4.9000,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (70 mg/mL) in healthy male adults.\",\"authors\":\"Monika Tomaszewska-Kiecana, Felicitas Bullo, Lukasz Jaskiewicz, Serena Stamatakos, Hendrik Otto, Masna Rai, Abid Sattar, Steffen Leutz, Fausto Berti\",\"doi\":\"10.1080/13543784.2025.2505469\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>This study (NCT05876949) compared the pharmacokinetic (PK) similarity, safety, and immunogenicity of AVT03, a candidate biosimilar, with reference product (RP) denosumab (Xgeva).</p><p><strong>Methods: </strong>Healthy male participants (<i>N</i> = 208, including 24 Japanese participants) were randomized 1:1 to receive one 120 mg dose of AVT03, or RP. PK similarity was demonstrated if the 90% confidence intervals (CI) for the ratio of geometric means for the primary PK parameters C<sub>max</sub> and AUC<sub>0-t</sub> were within 80.00% and 125.00%. Additional PK parameters included AUC<sub>0-inf</sub>, t<sub>max</sub>, K<sub>el</sub>, t<sub>1/2</sub>, V<sub>z</sub>/F, and CL/F. Safety and immunogenicity were also assessed.</p><p><strong>Results: </strong>The 90% CIs for the ratio of geometric means for the primary PK parameters were entirely contained within the prespecified margins of 80.00% and 125.00% (C<sub>max</sub> [98.26, 110.00]; AUC<sub>0-t</sub> [102.30, 113.60]), supporting demonstration of PK similarity. Consistency between Japanese participants and the overall population was shown. Safety and immunogenicity profiles were comparable between the two treatment arms.</p><p><strong>Conclusion: </strong>Results supported demonstration of PK similarity between AVT03 and RP. AVT03 had a safety and immunogenicity profile comparable to RP.</p><p><strong>Clinical trial registration: </strong>The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05876949); and 2022 -003,659-32 (EudraCT).</p>\",\"PeriodicalId\":12313,\"journal\":{\"name\":\"Expert opinion on investigational drugs\",\"volume\":\" \",\"pages\":\"1-8\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2025-05-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert opinion on investigational drugs\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/13543784.2025.2505469\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert opinion on investigational drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13543784.2025.2505469","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
A randomized, double-blind, single dose, parallel group, 2-arm study assessing the pharmacokinetic similarity, safety, tolerability, and immunogenicity profiles of biosimilar candidate AVT03 (70 mg/mL) in healthy male adults.
Background: This study (NCT05876949) compared the pharmacokinetic (PK) similarity, safety, and immunogenicity of AVT03, a candidate biosimilar, with reference product (RP) denosumab (Xgeva).
Methods: Healthy male participants (N = 208, including 24 Japanese participants) were randomized 1:1 to receive one 120 mg dose of AVT03, or RP. PK similarity was demonstrated if the 90% confidence intervals (CI) for the ratio of geometric means for the primary PK parameters Cmax and AUC0-t were within 80.00% and 125.00%. Additional PK parameters included AUC0-inf, tmax, Kel, t1/2, Vz/F, and CL/F. Safety and immunogenicity were also assessed.
Results: The 90% CIs for the ratio of geometric means for the primary PK parameters were entirely contained within the prespecified margins of 80.00% and 125.00% (Cmax [98.26, 110.00]; AUC0-t [102.30, 113.60]), supporting demonstration of PK similarity. Consistency between Japanese participants and the overall population was shown. Safety and immunogenicity profiles were comparable between the two treatment arms.
Conclusion: Results supported demonstration of PK similarity between AVT03 and RP. AVT03 had a safety and immunogenicity profile comparable to RP.
Clinical trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05876949); and 2022 -003,659-32 (EudraCT).
期刊介绍：
Expert Opinion on Investigational Drugs (ISSN 1354-3784 [print], 1744-7658 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles and original papers on drugs in preclinical and early stage clinical development, providing expert opinion on the scope for future development.
The Editors welcome:
Reviews covering preclinical through to Phase II data on drugs or drug classes for specific indications, and their potential impact on future treatment strategies
Drug Evaluations reviewing the clinical and pharmacological data on a particular drug
Original Research papers reporting the results of clinical investigations on agents that are in Phase I and II clinical trials
The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
