Study of Coagulation Factor VIIa Marzeptacog Alfa (Activated) in Subjects With Inherited Bleeding Disorders

Study Overview
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Brief Summary
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The purpose of the trial is to evaluate the PK, bioavailability, PD, efficacy and safety of MarzAA for on demand treatment and control of bleeding episodes in adult subjects with inherited bleeding disorders.

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

Conditions
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Factor VII Deficiency, Glanzmann Thrombasthenia, Hemophilia A With Inhibitor

Intervention / Treatment
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* Biological: Coagulation Factor VIIa variant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of cohort: FVII deficiency, Glanzmann Thrombasthenia, or hemophilia A with inhibitors Male or female, age 12 or older History of frequent bleeding episodes Affirmation of informed consent with signature confirmation and assent for children between ages 12 to 17 before any study related activities Agreement to use highly effective birth control throughout the study if the subject has childbearing potential Exclusion Criteria: Genotype of FVIID subjects with identified mutations by central lab at screening Previous participation in a clinical trial evaluating a modified rFVIIa agent Received an investigational drug within 30 days or 5 half-lives or absence of clinical effect, whichever is longer Known hypersensitivity to trial or related product Known positive antibody to FVII or FVIIa detected by central lab at screening Be immunosuppressed Significant contraindication to participate

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>For Phase 1, a Coagulation Factor VIIa variant by intravenous route, 18 μg/kg, followed by ascending doses by subcutaneous route, 10 μg/kg, 20 μg/kg, 30 μg/kg, 40 μg/kg, and 60 μg/kg, for PK and PD assessment. For Phase 2, Coagulation Factor VIIa, 20 μg/kg by subcutaneous route, administered on demand during bleeding episodes for a maximum of 3 doses as needed for hemostasis. | Biological: Coagulation Factor VIIa variant<br>* Single intravenous dose and ascending doses of subcutaneous injection of MarzAA, followed by a fixed dose of MarzAA for the treatment of bleeding episodes<br>* Other names: MarzAA;|
| Experimental: Cohort 2<br>For Phase 1, a Coagulation Factor VIIa variant by intravenous route, 18 μg/kg, followed by ascending doses by subcutaneous route, 30 μg/kg, 45 μg/kg, 60 μg/kg, 120 μg/kg, and 180 μg/kg, for PK and PD assessment. For Phase 2, Coagulation Factor VIIa, 60 μg/kg by subcutaneous route, administered on demand during bleeding episodes for a maximum of 3 doses as needed for hemostasis. | Biological: Coagulation Factor VIIa variant<br>* Single intravenous dose and ascending doses of subcutaneous injection of MarzAA, followed by a fixed dose of MarzAA for the treatment of bleeding episodes<br>* Other names: MarzAA;|
| Experimental: Cohort 3<br>For Phase 1, a Coagulation Factor VIIa variant by intravenous route, 18 μg/kg, followed by ascending doses by subcutaneous route, 30 μg/kg, 45 μg/kg, 60 μg/kg, 120 μg/kg, and 180 μg/kg, for PK and PD assessment. For Phase 2, Coagulation Factor VIIa, 60 μg/kg by subcutaneous route, administered on demand during bleeding episodes for a maximum of 3 doses as needed for hemostasis. | Biological: Coagulation Factor VIIa variant<br>* Single intravenous dose and ascending doses of subcutaneous injection of MarzAA, followed by a fixed dose of MarzAA for the treatment of bleeding episodes<br>* Other names: MarzAA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparative MarzAA activity by dose level/stage and confirm the Phase 2 dose | Comparative pharmacokinetics by dose level/stage based on examination of AUX for each of the dose groups in each cohort. | Dosing period for each stage in a cohort will be approximately 5 to 11 days | 
| Bleeding episode treatment success | Proportion of bleeding events treated with MarzAA achieving hemostatic efficacy based on a four-point scale according to the Investigator's assessment | 24 hours after the first administration of study drug |