Pharmacokinetic Bridging Between an Autoinjector and a Prefilled Syringe Following Subcutaneous Administration of Mirikizumab in Healthy Participants.

IF 4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-09-03 DOI:10.1007/s12325-025-03335-z

Xin Zhang, Yuki Otani, Christopher D Payne, Nathan J Morris, Laiyi Chua, Rodrigo Escobar, Sihe Wang, Galen Shi

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引用次数: 0

Abstract

Introduction: Mirikizumab, a humanized anti-interleukin-23p19 monoclonal antibody, is approved for the treatment of moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). Two phase 1, open-label, two-arm, randomized studies compared pharmacokinetics and safety of mirikizumab (200 mg, Study AMBW; 300 mg, Study AMBX) to establish bioequivalence. Mirikizumab was administered subcutaneously using an autoinjector or a prefilled syringe (PFS) as a single dose in healthy participants.

Methods: Participants (male and female) were randomized 1:1 to mirikizumab by a PFS (reference) and an autoinjector (test). Participants were sub-randomized (1:1:1) to one of three injection sites (abdomen, arm, thigh) and stratified into one of three weight groups. Primary endpoints were maximum observed drug concentration (C_max), and area under concentration versus time curves (time zero to infinity [AUC_0-∞]; time to last time point with measurable concentration [AUC_0-tlast]). Secondary objectives were safety and immunogenicity.

Results: In Study AMBW, 90% confidence intervals (CIs) for the ratios (autoinjector to PFS) of geometric least squares mean values for C_max, AUC_0-∞, and AUC_0-tlast were within prespecified bioequivalence limits (0.80-1.25). Similar results were observed in Study AMBX, after administration of mirikizumab 300 mg, with bioequivalence achieved for AUC_0-tlast and AUC_0-∞, while the upper bound of the 90% CI of the geometric least squares mean ratio for C_max was slightly above the bioequivalence upper threshold. Overall safety of mirikizumab was similar between devices in both studies. Immunogenicity was similar overall in Study AMBW, but slightly higher (autoinjector versus PFS) in Study AMBX.

Conclusion: Mirikizumab administered by autoinjector or PFS was considered bioequivalent at the 200-mg UC maintenance dose and the 300-mg CD maintenance dose. Safety and immunogenicity profiles were comparable between autoinjector and PFS. Availability of an autoinjector option may be preferred by some patients and may help improve patient adherence to treatment.

Clinical trial registration: ClinicalTrials.gov NCT04607733; NCT05069896.

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在健康受试者中皮下给药Mirikizumab后，自动注射器和预充注射器之间的药代动力学桥接。

Mirikizumab是一种人源化抗白细胞介素-23p19单克隆抗体，已被批准用于治疗中重度溃疡性结肠炎（UC）和克罗恩病（CD）。两项1期、开放标签、双臂、随机研究比较了mirikizumab （200mg，研究AMBW； 300mg，研究AMBX）的药代动力学和安全性，以建立生物等效性。Mirikizumab在健康参与者中使用自动注射器或预填充注射器（PFS）作为单剂量皮下给药。方法：参与者（男性和女性）通过PFS（参考）和自动注射器（测试）按1:1随机分配给mirikizumab。参与者被亚随机（1:1:1）分配到三个注射部位（腹部、手臂、大腿）中的一个，并被分层到三个体重组中的一个。主要终点为观察到的最大药物浓度（Cmax），以及浓度与时间曲线下的面积（从时间0到∞[AUC0-∞]；从时间到最后一个可测量浓度的时间点[AUC0-tlast]）。次要目标是安全性和免疫原性。结果：在AMBW研究中，Cmax、AUC0-∞和AUC0-tlast的几何最小二乘平均值（自进样器与PFS）的90%置信区间（CIs）在预先规定的生物等效性限值（0.80-1.25）内。在AMBX研究中也观察到类似的结果，在给予mirikizumab 300 mg后，AUC0-tlast和AUC0-∞实现了生物等效性，而Cmax的几何最小二乘平均比值的90% CI上界略高于生物等效性上限。在两项研究中，mirikizumab的总体安全性在设备之间相似。总体而言，研究AMBW的免疫原性相似，但研究AMBX的免疫原性略高（自动注射器与PFS）。结论：在200 mg UC维持剂量和300 mg CD维持剂量下，Mirikizumab通过自动注射器或PFS给药被认为是生物等效的。安全性和免疫原性在自动注射器和PFS之间具有可比性。一些患者可能更愿意选择自动注射器，这可能有助于提高患者对治疗的依从性。临床试验注册：ClinicalTrials.gov NCT04607733；NCT05069896。

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

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.