候选生物类似药 CT-P43 与乌司奴单抗在中重度斑块状银屑病中的疗效和安全性：一项随机、活性对照、双盲、III 期研究的 28 周结果。
Efficacy and Safety of Candidate Biosimilar CT-P43 Versus Originator Ustekinumab in Moderate to Severe Plaque Psoriasis: 28-Week Results of a Randomised, Active-Controlled, Double-Blind, Phase III Study.
机构信息
Alliance Clinical Trials and Probity Medical Research Inc., 135 Union Street East, Waterloo, ON, N2J 1C4, Canada.
University of Toronto, Toronto, ON, Canada.
出版信息
BioDrugs. 2024 Jan;38(1):121-131. doi: 10.1007/s40259-023-00630-5. Epub 2023 Nov 22.
BACKGROUND
CT-P43 is a candidate ustekinumab biosimilar in clinical development.
OBJECTIVES
This paper aims to demonstrate equivalent efficacy of CT-P43 to originator ustekinumab in adults with moderate to severe plaque psoriasis.
METHODS
This double-blind, phase III trial randomised patients (1:1) to receive subcutaneous CT-P43 or originator ustekinumab (45/90 mg for patients with baseline body weight ≤ 100 kg/> 100 kg) at week 0 and week 4 in Treatment Period I. Prior to week 16 dosing in Treatment Period II, patients receiving originator ustekinumab were re-randomised (1:1) to continue originator ustekinumab or switch to CT-P43; patients initially randomised to CT-P43 continued receiving CT-P43 (at weeks 16, 28 and 40). The primary endpoint of the trial was mean per cent improvement from baseline in Psoriasis Area Severity Index (PASI) score at week 12. Equivalence was concluded if confidence intervals (CIs) for the estimate of treatment difference were within pre-defined equivalence margins: ± 10% [90% CI; modified intent-to-treat set; Food and Drug Administration (FDA) approach] or ± 15% [95% CI; full analysis set for patients only receiving 45 mg doses in Treatment Period I; European Medicines Agency (EMA) approach]. Additional efficacy, pharmacokinetic, safety and immunogenicity endpoints were evaluated through week 52. Results to week 28 are reported here.
RESULTS
In Treatment Period I, 509 patients were randomised (CT-P43: N = 256; originator ustekinumab: N = 253). The mean per cent improvement in PASI score at week12 was 77.93% and 75.89% for CT-P43 and originator ustekinumab, respectively (FDA approach); per the EMA approach, corresponding values were 78.26% and 77.33%. Estimated treatment differences were 2.05 (90% CI -0.23, 4.32) and 0.94 (95% CI -2.29, 4.16); equivalence was achieved for both sets of assumptions. Further efficacy parameters and pharmacokinetic, safety and immunogenicity outcomes were comparable between treatment groups, including after switching from originator ustekinumab to CT-P43.
CONCLUSIONS
CT-P43 demonstrated equivalent efficacy to originator ustekinumab in patients with moderate to severe plaque psoriasis, with comparable pharmacokinetic, safety and immunogenicity profiles.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04673786; date of registration: 17 December, 2020.
背景
CT-P43 是一种在临床开发中的乌司奴单抗生物类似药。
目的
本研究旨在证明 CT-P43 在中重度斑块型银屑病成人患者中的疗效与原研乌司奴单抗相当。
方法
这是一项双盲、III 期临床试验，将患者（1:1）随机分配至皮下注射 CT-P43 或原研乌司奴单抗（基线体重≤100kg 的患者为 45/90mg，>100kg 的患者为 90mg），分别于第 0 周和第 4 周给药，为治疗期 I。在治疗期 II 的第 16 周给药前，接受原研乌司奴单抗治疗的患者被重新随机分组（1:1），继续接受原研乌司奴单抗或转换为 CT-P43；最初随机分配至 CT-P43 组的患者继续接受 CT-P43（第 16、28 和 40 周）。该试验的主要终点为第 12 周时，从基线到银屑病面积严重程度指数（PASI）评分的平均百分比改善。如果治疗差异估计值的置信区间（CI）在预先设定的等效性边界内，则认为等效：±10%（90%CI；改良意向治疗集；美国食品药品监督管理局（FDA）方法）或±15%（95%CI；仅接受治疗期 I 中 45mg 剂量的患者的全分析集；欧洲药品管理局（EMA）方法）。通过第 52 周评估额外的疗效、药代动力学、安全性和免疫原性终点。此处报告至第 28 周的结果。
结果
在治疗期 I 中，509 例患者被随机分组（CT-P43：N=256；原研乌司奴单抗：N=253）。第 12 周时，CT-P43 和原研乌司奴单抗组的 PASI 评分平均改善率分别为 77.93%和 75.89%（FDA 方法）；根据 EMA 方法，相应的值分别为 78.26%和 77.33%。估计的治疗差异分别为 2.05（90%CI -0.23，4.32）和 0.94（95%CI -2.29，4.16）；两种假设均达到等效性。两组的其他疗效参数和药代动力学、安全性和免疫原性结果相当，包括从原研乌司奴单抗转换为 CT-P43 后。
结论
CT-P43 在中重度斑块型银屑病患者中的疗效与原研乌司奴单抗相当，具有相似的药代动力学、安全性和免疫原性特征。
临床试验注册
ClinicalTrials.gov 标识符：NCT04673786；注册日期：2020 年 12 月 17 日。
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