医学
加药
队列
不利影响
药效学
临床终点
内科学
临床试验
药代动力学
随机对照试验
作者
Steven R. Lentz,Pratima Chowdary,Lidia Gil,Francisco José López-Jaime,Johnny Mahlangu,Irina Matytsina,Anne Louise Nielsen,Jerzy Windyga
标识
DOI:10.1016/j.jtha.2023.12.016
摘要
Background Mim8 (denecimig) is a factor VIII (FVIII) mimetic bispecific antibody in development for the treatment of hemophilia. Data from the phase 1 part of FRONTIER1 (EudraCT:2019-000465-20; NCT04204408; NN7769-4513) suggested that Mim8 was well tolerated in healthy participants and exhibited pharmacokinetic (PK) properties consistent with dose proportionality. Objectives The partially randomized, phase 2, multiple ascending dose (MAD) part of FRONTIER1 aimed to evaluate the safety, PK, pharmacodynamics (PD), and exploratory efficacy of Mim8 in participants with hemophilia A, with or without FVIII inhibitors. Methods The MAD part of FRONTIER1 consisted of 42 participants, assigned to 5 cohorts, with participants in cohorts 3 and 4 randomized 1:1 to dosing weekly or every 4 weeks, respectively. Four of the 42 participants (9.5%) had FVIII inhibitors prior to study enrolment. The primary endpoint was treatment-emergent adverse events (TEAEs). PK and PD were evaluated by Mim8 plasma concentration and thrombin generation, respectively. Exploratory efficacy was assessed via the number of treated bleeds. Safety and PD parameters were also evaluated from an exploratory cohort treated with emicizumab. Results Mim8 was well tolerated, with 1 serious TEAE (anxiety-related chest pain) deemed unrelated to Mim8. There was no dose dependency of the number, causality, type, or severity of TEAEs. PK/PD properties supported weekly to monthly dosing approaches, and few participants experienced treated bleeds beyond the lowest dose cohort (1 in cohorts 2 and 3, and 3 in cohort 5). Conclusions These data support the continued clinical development of Mim8, and FRONTIER1 has proceeded onto an extension phase.
科研通智能强力驱动
Strongly Powered by AbleSci AI