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FRONTIER1: a partially randomized phase 2 study assessing the safety, PK, and PD of Mim8, a factor VIIIa mimetic
Journal article   Open access   Peer reviewed

FRONTIER1: a partially randomized phase 2 study assessing the safety, PK, and PD of Mim8, a factor VIIIa mimetic

Steven R Lentz, Pratima Chowdary, Lidia Gil, Francisco J Lopez-Jaime, Johnny Mahlangu, Irina Matytsina, Anne Louise Nielsen and Jerzy Windyga
Journal of thrombosis and haemostasis, Vol.22(4), pp.990-1000
04/2024
DOI: 10.1016/j.jtha.2023.12.016
PMID: 38142846
url
https://doi.org/10.1016/j.jtha.2023.12.016View
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Abstract

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. 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. 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. 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). These data support the continued clinical development of Mim8, and FRONTIER1 has proceeded onto an extension phase.
 Pharmacokinetics Safety clinical trial hemophilia A factor VIII

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