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

Phase 1

Terminated

• Conditions: Hemophilia A With Inhibitor; Factor VII Deficiency; Glanzmann Thrombasthenia
• Interventions: Biological: Coagulation Factor VIIa variant

• Registration Number: NCT04548791
• Lead Sponsor: Catalyst Biosciences

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-08
• Study First Submitted QC: 2020-09-08
• Study First Posted: 2020-09-16
• Study Start: 2021-05-17
• Primary Completion: 2021-11-15
• Status Verified: 2021-12
• Study Completion: 2021-12-03
• Last Update Submitted: 2021-12-06
• Last Update Posted: 2021-12-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 19

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 2	Coagulation Factor VIIa variant	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.
Cohort 3	Coagulation Factor VIIa variant	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.
Cohort 1	Coagulation Factor VIIa variant	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.

Primary Outcome Measures

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

Trial Locations

Locations (20)

Careggi University Hospital; 🇮🇹 Florence, Italy

University of California -San Francisco; 🇺🇸 San Francisco, California, United States

Rush University; 🇺🇸 Chicago, Illinois, United States

Center for Thrombosis and Haemorrhagic Diseases; 🇮🇹 Milan, Italy

Michigan State University Center for Bleeding Disorders & Clotting Disorders; 🇺🇸 East Lansing, Michigan, United States

UC Davis Medical Center; 🇺🇸 Sacramento, California, United States

University of Colorado Hemophilia and Thrombosis Center; 🇺🇸 Aurora, Colorado, United States

Children's Hospital of Michigan; 🇺🇸 Detroit, Michigan, United States

Maggiore Polyclinic Hospital, IRCCS Ca' Granda; 🇮🇹 Milan, Italy

Children's Hospital BambiNo Gesù, IRCCS (PEDS); 🇮🇹 Roma, Italy

City of Health and Science of Turin; 🇮🇹 Turin, Italy

K. J. Somaiya Hospital and Research Centre; 🇮🇳 Mumbai, India

Institute of Blood Pathology and Transfusion Medicine, Department of Surgery and Clinical Transfusiology; 🇺🇦 Lviv, Ukraine

Sahyadri Super Speciality Hospital; 🇮🇳 Pune, India

East Carolina University; 🇺🇸 Greenville, North Carolina, United States

Mazumdar Shaw Medical Centre; 🇮🇳 Bengaluru, India

St. John's Medical College Hospital; 🇮🇳 Bengaluru, India

Territorial Clinical Hospital; 🇷🇺 Barnaul, Russian Federation

National Medical Hematology Research Center under the Ministry of Healthcare of the Russian Federation; 🇷🇺 Moscow, Russian Federation

Amrita Institute of Medical Sciences and Research Centre; 🇮🇳 Kochi, India