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

NCT04548791 | Terminated Phase 1 FDA Drug

• 1 other identifier: MAA-202
• Study Type: interventional
• Target: 19
• Locations: 5 countries
• Sites: 20

Brief Summary

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.

Conditions

Factor VII Deficiency; Glanzmann Thrombasthenia; Hemophilia A With Inhibitor

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (3)

Cohort 1

EXPERIMENTAL

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

Cohort 2

EXPERIMENTAL

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

Cohort 3

EXPERIMENTAL

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

Interventions

Coagulation Factor VIIa variant BIOLOGICAL

Single intravenous dose and ascending doses of subcutaneous injection of MarzAA, followed by a fixed dose of MarzAA for the treatment of bleeding episodes

Also known as: MarzAA

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Catalyst Biosciences: lead

Study Sites (20)

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California -San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado Hemophilia and Thrombosis Center

Aurora, Colorado, 80045, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Michigan State University Center for Bleeding Disorders & Clotting Disorders

East Lansing, Michigan, 49805, United States

Location

East Carolina University

Greenville, North Carolina, 27858, United States

Location

Mazumdar Shaw Medical Centre

Bengaluru, India

Location

St. John's Medical College Hospital

Bengaluru, India

Location

Amrita Institute of Medical Sciences and Research Centre

Kochi, India

Location

K. J. Somaiya Hospital and Research Centre

Mumbai, India

Location

Sahyadri Super Speciality Hospital

Pune, India

Location

Careggi University Hospital

Florence, Italy

Location

Center for Thrombosis and Haemorrhagic Diseases

Milan, Italy

Location

Maggiore Polyclinic Hospital, IRCCS Ca' Granda

Milan, Italy

Location

Children's Hospital BambiNo Gesù, IRCCS (PEDS)

Roma, Italy

Location

City of Health and Science of Turin

Turin, Italy

Location

Territorial Clinical Hospital

Barnaul, Russia

Location

National Medical Hematology Research Center under the Ministry of Healthcare of the Russian Federation

Moscow, Russia

Location

Institute of Blood Pathology and Transfusion Medicine, Department of Surgery and Clinical Transfusiology

Lviv, Ukraine

Location

MeSH Terms

Conditions

Factor VII Deficiency; Thrombasthenia

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Blood Platelet Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: September 16, 2020
• Study Start: May 17, 2021
• Primary Completion: November 15, 2021
• Study Completion: December 3, 2021
• Last Updated: December 21, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

IN (5); US (7); IT (5); RU (2); UA (1)