Study of Coagulation Factor VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia A and B

NCT03407651 | Completed Phase 2 Results FDA Drug

• 1 other identifier: MAA-201
• Study Type: interventional
• Target: 11
• Locations: 5 countries
• Sites: 9

Brief Summary

Phase 2, multi-center, open-label study designed to evaluate the PK, bioavailability, PD, efficacy and safety of a daily subcutaneous \[SC\] treatment regimen with MarzAA for bleeding prophylaxis in 12 adult subjects with hemophilia A or B with an inhibitor and history of frequent spontaneous bleeding episodes.

Conditions

Hemophilia A With Inhibitor; Hemophilia B With Inhibitor

Outcome Measures

Primary Outcomes (1)

• Bleeding Episode Prevention Success

  Annualized bleed rate (ABR; spontaneous and total) during Part 2 when on final MarzAA dose level versus recorded historical ABR. The analysis of the primary endpoint (annualized bleeding rate ABR for spontaneous and traumatic bleeds) of the final dose of MarzAA each subject was treated was based on the 1-sample test compared to a predefined rate assumed for the on-demand therapy. The latter was assumed to be 12 (or 1 bleed per month), which was the minimum ABR for each subject according to inclusion criterion 2 (defined as the H0), with no maximum value. A higher score indicated a worse outcome. ABR is on a scale of 0 to 365, with a lower score reflective of a lower number of bleeding events in a year.

  Day 1 of final MarzAA dose level - Day 50

Secondary Outcomes (8)

• Occurrence of Breakthrough Bleeding

  From Day 5 of dose level until occurrence of event

• Occurrence of Clinical Thrombotic Event

  From date of first dose until date of first occurrence of clinical event, assessed up to treatment Day 50

• Coagulation Assessment - Prothrombin Time

  From date of pre-dose to 24 hours (Part 1a), pre-dose to 48 hours (Part 1b), and pre-dose to Day 50 (Part 2)

• Coagulation Assessment - Activated Partial Thromboplastin Time

  From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), to Day 50/end of study (Part 2)

• Coagulation Assessment - Fibrinogen

  From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), or Day 50 (Part 2).

Study Arms (3)

Part 1a

EXPERIMENTAL

Coagulation Factor VIIa variant, 18 µg/kg by intravenous route

Biological: Coagulation Factor VIIa variant

Part 1b

EXPERIMENTAL

Coagulation Factor VIIa variant, 30 µg/kg by subcutaneous route

Biological: Coagulation Factor VIIa variant

Part 2

EXPERIMENTAL

Coagulation Factor VIIa variant, 30, 60, 90, 120 µg/kg by subcutaneous route

Biological: Coagulation Factor VIIa variant

Interventions

Coagulation Factor VIIa variant BIOLOGICAL

Single intravenous injection of MarzAA, followed by single subcutaneous injection of MarzAA, followed by daily subcutaneous injection of MarzAA for 50 days at final dose level required.

Part 1a; Part 1b; Part 2

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Severe congenital hemophilia A or B with an inhibitor.
• History of frequent spontaneous bleeding episodes.
• Male, age 18 or older.
• Affirmation of informed consent with signature confirmation before any trial-related activities.

You may not qualify if:

• Receiving prophylaxis treatment.
• Previous participation in a clinical trial evaluating a modified rFVIIa agent.
• Known positive antibody to FVII or FVIIa detected by central laboratory at screening.
• Have a coagulation disorder other than hemophilia A or B.
• Significant contraindication to participation.

Sponsors & Collaborators

• Catalyst Biosciences: lead

Study Sites (9)

Hematology Center after Prof. R. Yeolyan

Yerevan, Armenia

Location

JSC "K.Eristavi National Center of Experimental and Clinical Surgery"

Tbilisi, Georgia

Location

LTD M.Zodelava Hematology Centre

Tbilisi, Georgia

Location

LTD Medinvest - Institute of Hematology and Transfusiology

Tbilisi, Georgia

Location

Gabinet Lekarski, Bartosz Korczowski

Rzeszów, Poland

Location

Regional Clinical Hospital

Kemerovo, Russia

Location

FGU Kirov Scientific Research

Kirov, Russia

Location

Center for Hemophilia Treatment

Saint Petersburg, Russia

Location

Haemophilia Comprehensive Care Centre

Johannesburg, South Africa

Location

Limitations and Caveats

A planned outcome measure (coagulation assessment via MarzAA activity levels) of the protocol was not calculated as as a satisfactory assay could not be developed. Data is not reported for two allowed dose groups in Part 2, MarzAA 90 μg and 120 μg, as no subjects were treated at these dose levels

Results Point of Contact

• Title: Howard Levy, Chief Medical Officer
• Organization: Catalyst Biosciences

hlevy@catbio.com

+1.650.266.6871

Study Officials

• Howard Levy, MD, PhD, MMM

  Catalyst Biosciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2018
• First Posted: January 23, 2018
• Study Start: December 18, 2017
• Primary Completion: March 15, 2019
• Study Completion: April 13, 2019
• Last Updated: September 23, 2021
• Results First Posted: September 23, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1); AR (1); GE (3); PL (1); RU (3)