Repeated Switching Between CT-P17 and EU Reference Adalimumab in Patients with Moderate-to-Severe Chronic Plaque Psoriasis: A Randomized, Double-Blind, Active-Controlled, Phase 3, Interchangeability Study

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-02-11 DOI:10.1007/s12325-024-03100-8

Mark G. Lebwohl, John Y. Koo, Janusz Jaworski, Jakub Trefler, Stefan Daniluk, Anna Dudek, Wojciech Baran, Witold Owczarek, Joanna Kolinek, Paweł Brzewski, Mariusz Sikora, Marek Krogulec, SungHyun Kim, YunJu Bae, DaBee Jeon, EunJin Choi, JungBin Cha, HyunJin Lee, SuJin Choi, David M. Pariser

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引用次数: 0

Abstract

Introduction

This study aimed to demonstrate the interchangeability of biosimilar CT-P17 and European Union reference adalimumab (EU-adalimumab) in a repeated-switch scenario.

Methods

In this ongoing, randomized, double-blind, active-controlled, phase 3 study, adults with moderate-to-severe plaque psoriasis received 80 mg EU-adalimumab on day 1, then 40 mg 1 week later and every other week until week 11. At week 13, patients were randomized (1:1, via an interactive web response system) to continue EU-adalimumab (“continuous” group) or undergo repeated switches between CT-P17 and EU-adalimumab (“switching” group). Dosing was via subcutaneous administration. The primary endpoints were area under the concentration–time curve and maximum serum concentration between weeks 25 and 27 (AUC_tau,W25–27 and C_max,W25–27, respectively). Secondary endpoints comprised additional pharmacokinetic (PK) parameters, efficacy, safety, and immunogenicity. Week 27 findings are presented.

Results

The first patient provided signed informed consent on November 7, 2022. Week 27 visits were completed by August 14, 2023. Of 367 patients enrolled, 346 were randomized (switching group, n = 172; continuous group, n = 174). The ratios of least squares means between groups and associated 90% confidence intervals (CIs) for AUC_tau,W25–27 and C_max,W25–27 were 99.45% (94.11–105.08%) and 100.45% (95.03–106.17%), respectively. For both endpoints, 90% CIs fell within the predefined equivalence margin of 80–125% and criteria were greater than calculated t values, satisfying bioequivalence. Additional PK endpoints and efficacy, safety, and immunogenicity findings were similar between groups. Safety profiles were in line with those previously reported.

Conclusions

Week 27 primary PK results demonstrated bioequivalence, and the overall study results supported the interchangeability of CT-P17 and EU-adalimumab.

Trial Registration

ClinicalTrials.gov, NCT05495568.

查看原文本刊更多论文

在中重度慢性斑块性银屑病患者中反复切换CT-P17和欧盟参考阿达木单抗：一项随机，双盲，主动对照，3期，互换性研究

本研究旨在证明生物仿制药CT-P17和欧盟参考药物阿达木单抗（EU-adalimumab）在重复切换情况下的互换性。方法：在这项正在进行的随机、双盲、主动对照的3期研究中，患有中度至重度斑块性银屑病的成年人在第1天接受80 mg EU-adalimumab治疗，1周后接受40 mg治疗，每隔一周接受一次，直到第11周。在第13周，患者被随机分配（1:1，通过交互式网络响应系统）继续使用eu -阿达木单抗（“连续”组）或在CT-P17和eu -阿达木单抗（“切换”组）之间反复切换。通过皮下给药给药。主要终点为第25周至第27周的浓度-时间曲线下面积和最大血清浓度（AUCtau，W25-27和Cmax，W25-27）。次要终点包括额外的药代动力学（PK）参数、有效性、安全性和免疫原性。报告第27周的研究结果。结果：第一位患者于2022年11月7日签署知情同意书。第27周的访问于2023年8月14日完成。在入组的367例患者中，346例被随机分组(切换组，n = 172；连续组，n = 174)。AUCtau、W25-27和Cmax、W25-27的组间最小二乘均值比值及相关90%置信区间（ci）分别为99.45%（94.11 ~ 105.08%）和100.45%（95.03 ~ 106.17%）。在这两个终点，90%的ci落在预定的80-125%的等效范围内，并且标准大于计算的t值，满足生物等效性。其他PK终点、疗效、安全性和免疫原性发现在两组之间相似。安全概况与之前报道的一致。结论：第27周初步PK结果显示生物等效性，总体研究结果支持CT-P17和eu -阿达木单抗的互换性。试验注册：ClinicalTrials.gov, NCT05495568。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.