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

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

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.

Study Overview

• Status: Terminated
• Conditions: Factor VII Deficiency; Hemophilia A With Inhibitor; Glanzmann Thrombasthenia
• Intervention / Treatment: Biological: Coagulation Factor VIIa variant

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• India
  • Bengaluru, India
    • Mazumdar Shaw Medical centre
  • Bengaluru, India
    • St. John's Medical College Hospital
  • Kochi, India
    • Amrita Institute of Medical Sciences and Research Centre
  • Mumbai, India
    • K. J. Somaiya Hospital and Research Centre
  • Pune, India
    • Sahyadri Super Speciality Hospital
• Italy
  • Florence, Italy
    • Careggi University Hospital
  • Milan, Italy
    • Center for Thrombosis and Haemorrhagic Diseases
  • Milan, Italy
    • Maggiore Polyclinic Hospital, IRCCS Ca' Granda
  • Roma, Italy
    • Children's Hospital BambiNo Gesù, IRCCS (PEDS)
  • Turin, Italy
    • City of Health and Science of Turin
• Russian Federation
  • Barnaul, Russian Federation
    • Territorial Clinical Hospital
  • Moscow, Russian Federation
    • National Medical Hematology Research Center under the Ministry of Healthcare of the Russian Federation
• Ukraine
  • Lviv, Ukraine
    • Institute of Blood Pathology and Transfusion Medicine, Department of Surgery and Clinical Transfusiology
• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Francisco, California, United States, 94143
      • University of California -San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hemophilia and Thrombosis Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
    • East Lansing, Michigan, United States, 49805
      • Michigan State University Center for Bleeding Disorders & Clotting Disorders
  • North Carolina
    • Greenville, North Carolina, United States, 27858
      • East Carolina University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 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; Single intravenous dose and ascending doses of subcutaneous injection of MarzAA, followed by a fixed dose of MarzAA for the treatment of bleeding episodes; Other Names: MarzAA
Experimental: Cohort 2; 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; Single intravenous dose and ascending doses of subcutaneous injection of MarzAA, followed by a fixed dose of MarzAA for the treatment of bleeding episodes; Other Names: MarzAA
Experimental: Cohort 3; 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; Single intravenous dose and ascending doses of subcutaneous injection of MarzAA, followed by a fixed dose of MarzAA for the treatment of bleeding episodes; Other Names: MarzAA

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Catalyst Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2021
• Primary Completion (Actual): November 15, 2021
• Study Completion (Actual): December 3, 2021

Study Registration Dates

• First Submitted: September 8, 2020
• First Submitted That Met QC Criteria: September 8, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2021
• Last Update Submitted That Met QC Criteria: December 6, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Platelet Disorders; Hemostatic Disorders; Hemophilia A; Blood Coagulation Disorders; Factor VII Deficiency; Thrombasthenia
• Other Study ID Numbers: MAA-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No