Pharmacokinetics, Safety, and Immunogenicity of DMB-3115, a Ustekinumab Biosimilar for Immune-Mediated Diseases, in Healthy Japanese Male Participants: A Randomized, Double-Blind, Single-Dose Study.

IF 4.7 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2026-08-14 DOI:10.1007/s12325-026-03755-5

Hironori Konishi, Yuji Kumagai, Takeyuki Shindo, Michio Yagi, Takashi Eto, Rie Yazawa, Makoto Yono, Naoki Cho, Hideki Fushimi, Jun Morita

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引用次数: 0

Abstract

Introduction: DMB-3115 is a biosimilar to ustekinumab (Stelara®). We conducted a randomized controlled study to determine the similarity of bioavailability between DMB-3115 and Stelara (distributed in Japan) in healthy Japanese participants.

Methods: Healthy Japanese male participants aged 18 to 55 years were randomly assigned in a 1:1 ratio to receive a single subcutaneous injection (45 mg) of DMB-3115 or Stelara. Participants were followed for 112 days. The primary pharmacokinetic (PK) endpoints were area under the concentration-time curve from time zero to the final sampling time point t (AUC_t) and maximum serum concentration (C_max).

Results: This study was conducted between April 11, 2022 and November 22, 2022. A total of 150 participants (75 in each group) received the study drug and were included in the safety analysis, whereas 147 participants (74 in the DMB-3115 group and 73 in the Stelara group) with properly measured PK data were included in the PK analysis. The 90% confidence interval (CI) for the geometric least squares mean (LSM) ratio (DMB-3115/Stelara) of AUC_t (n = 74/73) ranged from 0.826 to 1.011, which was contained within the prespecified bioequivalence range of 0.80 to 1.25. By contrast, the 90% CI for the geometric LSM ratio of C_max (n = 74/73) ranged from 0.762 to 0.984. The proportion of participants experiencing any adverse event (AE) was 37.3% (28 participants) in the DMB-3115 group and 48.0% (36 participants) in the Stelara group. The most common AE in the DMB-3115 group (n = 75) was blood creatine phosphokinase increased. All AEs were mild or moderate in severity. The proportions of participants with post-dose anti-drug antibodies and neutralizing antibodies were lower in the DMB-3115 group (n = 75).

Conclusion: Bioavailability of DMB-3115 was considered similar to that of Stelara in the Japanese population. DMB-3115 was well tolerated without any new safety concern.

Trial registration: Clinical Trial Registration Japan Registry of Clinical Trials (jRCT2071210135; registered March 22, 2022).

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DMB-3115（一种用于免疫介导疾病的Ustekinumab生物类似药）在健康日本男性受试者中的药代动力学、安全性和免疫原性：一项随机、双盲、单剂量研究

DMB-3115是ustekinumab （Stelara®）的生物类似药。我们进行了一项随机对照研究，以确定DMB-3115和Stelara（分布在日本）在健康日本参与者中的生物利用度相似性。方法：年龄在18至55岁之间的健康日本男性参与者按1:1的比例随机分配接受单次皮下注射（45 mg） DMB-3115或Stelara。参与者被跟踪了112天。主要药代动力学终点为从时间0到最终采样时间点t的浓度-时间曲线下面积（AUCt）和最大血清浓度（Cmax）。结果：本次研究时间为2022年4月11日至2022年11月22日。共有150名参与者（每组75名）接受了研究药物，并被纳入安全性分析，而147名参与者（DMB-3115组74名，Stelara组73名）有适当的PK数据被纳入PK分析。AUCt （n = 74/73）的几何最小二乘平均（LSM）比（DMB-3115/Stelara）的90%置信区间（CI）为0.826 ~ 1.011，其生物等效性范围为0.80 ~ 1.25。相比之下，Cmax的几何LSM比率（n = 74/73）的90% CI范围为0.762 ~ 0.984。DMB-3115组出现任何不良事件（AE）的比例为37.3%（28人），Stelara组为48.0%（36人）。DMB-3115组（n = 75）最常见的AE是血肌酸磷酸激酶升高。所有ae的严重程度均为轻度或中度。DMB-3115组中出现给药后抗药物抗体和中和抗体的比例较低（n = 75）。结论：DMB-3115在日本人群中的生物利用度与Stelara相似。DMB-3115耐受性良好，没有任何新的安全性问题。试验注册：临床试验注册日本临床试验注册中心（jRCT2071210135，于2022年3月22日注册）。

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.