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

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ClinicalTrials.gov Identifier: NCT03407651
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : December 10, 2018
Sponsor:
Information provided by (Responsible Party):
Catalyst Biosciences

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.

Condition or disease Intervention/treatment Phase
Hemophilia A With Inhibitor Hemophilia B With Inhibitor Biological: Coagulation Factor VIIa variant Phase 2

Detailed Description:

Multi-center, open-label Phase 2 study to evaluate the PK, bioavailability, PD, efficacy and safety of a daily SC treatment regimen with MarzAA for bleeding prophylaxis in adult subjects with hemophilia A or B with an inhibitor. The study will enroll and dose, both intravenously and subcutaneously, a total of 12 adult male subjects with severe congenital hemophilia A or B with an inhibitor, and history of frequent bleeding episodes during the 6 months prior to enrollment, as per the individual's bleeding and treatment records.

Once a subject is enrolled into the trial, the study will be conducted in three parts (occurring consecutively):

Part 1a (24 hours): Single IV administration of MarzAA; Part 1b (48 hours): Single SC administration of MarzAA; Part 2: Daily SC administration. Dose escalation in Part 2 will occur if breakthrough bleeding occurs. Subjects are treated for 50 days at the final dose level required.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Study to Evaluate the Pharmacokinetics, Efficacy and Safety of a Daily Subcutaneous Treatment Regimen With Marzeptacog Alfa (Activated) for Bleeding Prophylaxis in Adult Subjects With Hemophilia A and B Subjects With an Inhibitor
Actual Study Start Date : December 18, 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding Hemophilia

Arm Intervention/treatment
Experimental: Part 1a
Coagulation Factor VIIa variant, 18 µg/kg by intravenous route
Biological: Coagulation Factor VIIa variant
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.

Experimental: Part 1b
Coagulation Factor VIIa variant, 30 µg/kg by subcutaneous route
Biological: Coagulation Factor VIIa variant
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.

Experimental: Part 2
Coagulation Factor VIIa variant, 30, 60, 90, 120 µg/kg by subcutaneous route
Biological: Coagulation Factor VIIa variant
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.




Primary Outcome Measures :
  1. Bleeding episode treatment success [ Time Frame: Day 1 of final MarzAA dose level - Day 50 ]
    Annualized bleed (spontaneous and total) rate during Part 2 when on final MarzAA dose level versus recorded historical ABR


Secondary Outcome Measures :
  1. Occurrence of breakthrough bleeding [ Time Frame: From Day 5 of dose level until occurrence of event ]
    Occurrence of breakthrough bleeds requiring escalation to higher dose level.

  2. Occurrence of clinical thrombotic event [ Time Frame: From date of first dose until date of first occurrence of clinical event, assessed up to treatment Day 50 ]
    Occurrence of clinical thrombotic event not attributable to another cause.

  3. Coagulation assessment - prothrombin time [ Time Frame: From date of IV pre-dose to 5 and 30 minutes and Hour (hr) 1, 3, 6, 9, 12, and 24 post-dose. From date SC pre-dose and 3, 5, 7, 9, 12, 24, 30, and 48 hr post-dose. From date of daily SC pre-dose Day 1 of dose ]
    Change in coagulation parameter (prothrombin time [PT]) from pre-dose. The frequencies of these events will be summarized as proportions and counts.

  4. Coagulation assessment - activated partial thromboplastin time [ Time Frame: From date of IV pre-dose to 5 and 30 minutes and Hour (hr) 1, 3, 6, 9, 12, and 24 post-dose. From date SC pre-dose and 3, 5, 7, 9, 12, 24, 30, and 48 hr post-dose. From date of daily SC pre-dose Day 1 of dose ]
    Change in coagulation parameter (activated partial thromboplastin time [aPTT]) from pre-dose. The frequencies of these events will be summarized as proportions and counts.

  5. Coagulation assessment - fibrinogen [ Time Frame: From date of IV pre-dose to 5 and 30 minutes and Hour (hr) 1, 3, 6, 9, 12, and 24 post-dose. From date SC pre-dose and 3, 5, 7, 9, 12, 24, 30, and 48 hr post-dose. From date of daily SC pre-dose Day 1 of dose ]
    Change in coagulation parameter (fibrinogen) from pre-dose. The frequencies of these events will be summarized as proportions and counts.

  6. Coagulation assessment - MarzAA antigen and activity levels [ Time Frame: From date of IV pre-dose to 5 and 30 minutes and Hour (hr) 1, 3, 6, 9, 12, and 24 post-dose. From date SC pre-dose and 3, 5, 7, 9, 12, 24, 30, and 48 hr post-dose. From date of daily SC pre-dose Day 1 of dose ]
    Change in coagulation parameter (MarzAA antigen and activity levels) from pre-dose. The frequencies of these events will be summarized as proportions and counts.

  7. Coagulation assessment - thrombin generation time [ Time Frame: From date of IV pre-dose to 5 and 30 minutes and Hour (hr) 1, 3, 6, 9, 12, and 24 post-dose. From date SC pre-dose and 3, 5, 7, 9, 12, 24, 30, and 48 hr post-dose. From date of daily SC pre-dose Day 1 of dose ]
    Change in coagulation parameter (thrombin generation time [TGT]) from pre-dose. The frequencies of these events will be summarized as proportions and counts.

  8. Occurrence of antibody formation [ Time Frame: From date of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50. ]
    Occurrence of antibody formation resulting in a decreased endogenous level of coagulation Factor VII (FVII).

  9. Occurrence of an antibody response [ Time Frame: From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50. ]
    Occurrence of an antibody response to MarzAA and whether it is inhibitory and cross-reactive to wild-type recombinant coagulation FVII (wt-rFVII) or wt-FVIIa.

  10. Thrombogenicity assessment [ Time Frame: From time of pre-dose of MarzAA at Day 1 until date of first occurrence of thrombotic event, assessed up to treatment Day 50. ]
    Clinically significant levels of thrombogenicity markers (D-dimer, Prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin complex (TAT))



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03407651


Contacts
Contact: Howard Levy, MD, PhD, MMM +1.650.266.8671 hlevy@catbio.com

Locations
Armenia
Hematology Center after Prof. R. Yeolyan Recruiting
Yerevan, Armenia
Georgia
JSC "K.Eristavi National Center of Experimental and Clinical Surgery" Recruiting
Tbilisi, Georgia
LTD M.Zodelava Hematology Centre Recruiting
Tbilisi, Georgia
LTD Medinvest - Institute of Hematology and Transfusiology Recruiting
Tbilisi, Georgia
Poland
Gabinet Lekarski, Bartosz Korczowski Active, not recruiting
Rzeszów, Poland
Russian Federation
Regional Clinical Hospital Recruiting
Kemerovo, Russian Federation
FGU Kirov Scientific Research Not yet recruiting
Kirov, Russian Federation
Center for Hemophilia Treatment Not yet recruiting
Saint Petersburg, Russian Federation
South Africa
Haemophilia Comprehensive Care Centre Recruiting
Johannesburg, South Africa
Sponsors and Collaborators
Catalyst Biosciences
Investigators
Study Director: Howard Levy, MD, PhD, MMM Catalyst Biosciences

Responsible Party: Catalyst Biosciences
ClinicalTrials.gov Identifier: NCT03407651     History of Changes
Other Study ID Numbers: MAA-201
First Posted: January 23, 2018    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: This is an open label study so each investigator will have full access to all study subject data that is entered into the database

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Factor VIII
Coagulants