Phase 1/2 Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Marzeptacog Alfa (activated) in the Treatment of Episodic Bleeding in Subjects with Inherited Bleeding Disorders

Background There are many inherited conditions that present with episodic bleeding effectively treated with Factor VIIa (FVIIa). These include Factor VII deficiency (FVIID), an autosomal recessive disorder caused by ineffective or reduced levels of FVII, Glanzmann thrombasthenia (GT), a rare platelet disorder associated with a deficiency or dysfunction of glycoprotein IIb/IIIa, Hemophilia A with inhibitors (HawI), an X-linked, recessive, bleeding disorder caused by a deficiency of FVIII with development of inhibitors against FVIII, rendering them refractory to replacement treatment. Although emicizumab prophylaxis is available for HAwI (HAwI-E), breakthrough bleeding still occurs. Treatment of episodic bleeding requires technical expertise to gain the requisite intravenous (IV) access and is often associated with pain. This causes delays in administration which results in prolonged bleeding and accumulation of blood in the joint or other bleeding sites. Currently approved FVIIa containing products take 6-24 hours to achieve hemostasis and maintain efficacy. Marzeptacog alfa (activated) (MarzAA), a novel variant activated recombinant FVII (rFVIIa), is being developed for subcutaneous (SQ) administration to address this important unmet need. Data from the Phase 1 study, MAA-102, demonstrated that SQ MarzAA is quickly absorbed and has the potential to achieve and maintain plasma levels in the desired range with an acceptable safety profile. This open-label, multi-center, Phase 1/2 study is designed to evaluate the pharmacokinetics, pharmacodynamics, safety and efficacy of MarzAA for on-demand treatment of spontaneous or traumatic bleeds in adolescents and adults with FVIID (cohort 1), GT (cohort 2) and HAwI-E (cohort 3). It is estimated that 24 subjects will be enrolled across all 3 cohorts at approximately 25 sites in 5 countries. Study Design and Methods Key inclusion criteria:Eligible male or female subjects, ≥ 12 years of age must have confirmed diagnosis of: FVIID (cohort 1), GT (cohort 2) or HAwI treated with the same dose of emicizumab for at least 4 weeks, HAwI-E (cohort 3); history of bleeding with annualized bleeding rate (ABR) of ≥ 8 for cohorts 1 and 2 and ABR of ≥ 1 for cohort 3; investigator-confirmed subject’s ability to identify bleeds and administer MarzAA SQ at home. Key exclusion criteria:Subjects should not have previous exposure to SQ administration of rFVIIa or exposure to any other variant rFVIIa; known positive antibody or hypersensiti