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.

IF 4.9 2区医学 Q1 PHARMACOLOGY & PHARMACY

Expert opinion on investigational drugs Pub Date : 2025-05-16 DOI:10.1080/13543784.2025.2505469

Monika Tomaszewska-Kiecana, Felicitas Bullo, Lukasz Jaskiewicz, Serena Stamatakos, Hendrik Otto, Masna Rai, Abid Sattar, Steffen Leutz, Fausto Berti

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引用次数: 0

Abstract

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 C_max and AUC_0-t were within 80.00% and 125.00%. Additional PK parameters included AUC_0-inf, t_max, K_el, t_1/2, V_z/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% (C_max [98.26, 110.00]; AUC_0-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).

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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。

背景：本研究（NCT05876949）比较了候选生物类似药AVT03与参比产品（RP） denosumab （Xgeva）的药代动力学（PK）相似性、安全性和免疫原性。方法：健康男性受试者（N = 208，包括24名日本受试者）以1:1的比例随机分配，接受1次120 mg剂量的AVT03或RP。当主要PK参数Cmax和AUC0-t的几何平均比值的90%置信区间（CI）分别在80.00%和125.00%之间时，表明PK相似。其他PK参数包括AUC0-inf、tmax、Kel、t1/2、Vz/F和CL/F。安全性和免疫原性也进行了评估。结果：主要药代动力学参数几何均数比值的90% ci完全包含在80.00%和125.00%的预定范围内(Cmax [98.26, 110.00]；AUC0-t[102.30, 113.60])，支持PK相似性的论证。日本参与者与总体人口之间的一致性得到了证明。安全性和免疫原性在两个治疗组之间具有可比性。结论：AVT03与RP之间存在PK相似性。AVT03具有与RP相当的安全性和免疫原性。临床试验注册：临床试验在ClinicalTrials.gov注册（CT.gov标识符：NCT05876949）；2022 -003,659-32（草案）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert opinion on investigational drugs 医学-药学

CiteScore

10.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

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.