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Completed

NCT Number: NCT04072237

Study of Coagulation Faction VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia

This multi-center, open label Phase 1 study will evaluate the pharmacokinetics, pharmacodynamics, and safety of a single IV dose of MarzAA followed by ascending single SC doses of MarzAA in adult subjects with moderate or severe Hemophilia A or B, with or without an inhibitor.

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Key information

Conditions

Hemophilia A Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Coagulation Protein Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Genetic Diseases, X-Linked Hematologic Diseases Hemic and Lymphatic Diseases Hemophilia A With Inhibitor Hemophilia A Without Inhibitor Hemophilia B Hemophilia B With Inhibitor Hemophilia B Without Inhibitor Hemorrhagic Disorders

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Medical Center "Hippocrates - N", Plovdiv, Bulgaria

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About this study

This multi-center, open label Phase 1 study will evaluate the pharmacokinetics, pharmacodynamics, and safety of a single IV dose of MarzAA followed by ascending single SC doses of MarzAA in adult subjects with moderate or severe Hemophilia A or B, with or without an inhibitor. The study will enroll at least 8 adult male subjects with moderate or severe Hemophilia A or B with or without an inhibitor, in each dosing stage. Each subject will receive escalating doses of MarzAA for each stage of the study (except for Stage 5, where subjects receive the same dose as in Stage 4 split between two anatomical sites).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Moderate or severe congenital Hemophilia A or B, with or without an inhibitor
  • Male, age 18 or older
  • Affirmation of informed consent with signature confirmation before any trial related activities

Exclusion criteria

  • Inability to discontinue and washout prophylaxis treatment 72 hours prior to dosing.
  • Previous participation in a trial involving SC Administration of rFVIIa or any trial using a modified amino-acid sequence FVIIa
  • Known positive antibody to FVII or FVIIa detected by central laboratory at screening
  • Have a coagulation disorder other than hemophilia A or B, with or without an inhibitor
  • Significant contraindication to participate

Treatment and study plan

MarzAA (marzeptacog alfa [activated])

Biological

Single intravenous dose and ascending doses of subcutaneous injection of MarzAA (Coagulation Faction VIIa Variant)

Primary outcomes

  1. Comparative MarzAA Activity by Dose Level/Stage - AUC0-∞ and AUC0-last

    Time frame: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

    Comparative pharmacokinetics (PK) by dose level/stage based on examination of AUC frequencies of these for each of the dose groups

  2. Comparative MarzAA Activity by Dose Level/Stage - AUCT1-T2 Normalized by Dose = AUC0-last/Dose

    Time frame: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

    Comparative pharmacokinetics by dose level/stage based on examination of AUC frequency of these for each of the dose groups

Secondary outcomes

  1. Comparative MarzAA Activity of Intravenous and Subcutaneous - Cmax

    Time frame: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

    Change in Cmax at each stage for each dose group

  2. Comparative MarzAA Activity of Intravenous and Subcutaneous - Tmax

    Time frame: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

    Change in Tmax at each stage for each dose group

  3. Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2eqα

    Time frame: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

    Change in T1/2eqα at each stage for each dose group

  4. Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2λ-z

    Time frame: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

    Change in T1/2λ-z at each stage for each dose group

  5. Comparative MarzAA Activity of Intravenous and Subcutaneous - CL

    Time frame: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

    Change in CL at each stage for each dose group

  6. Comparative MarzAA Activity of Intravenous and Subcutaneous - Vd1

    Time frame: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

    Change in Vd1 at each stage for each dose group

  7. Comparative MarzAA Activity of Intravenous and Subcutaneous - BAabs

    Time frame: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

    Change in BAabs at each stage for each dose group

  8. Comparative MarzAA Activity of Intravenous and Subcutaneous - Mean Residence Time

    Time frame: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

    Change in Mean Residence Time at each stage for each dose group

  9. Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC From T1 to T2 Norm by Dose

    Time frame: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

    PK analysis by route of administration, dose level/stage of the study based on examination of AUC for each of the dose groups.

    Split dose (2*30 µg/kg) vs. (60 µg/kg)

  10. Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC Infinity Obs and AUC to Last Nonzero Conc

    Time frame: Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing, depending on participation in all 9 stages and time elapsed between each study stage.

    PK analysis by route of administration, dose level/stage of the study based on examination of AUC for each of the dose groups.

    Split dose (2*30 µg/kg) vs. (60 µg/kg)

  11. Change in Coagulation Parameters - Prothrombin Time (PT)

    Time frame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-7 (SC).

    Maximum change in PT from pre-dose

  12. Change in Coagulation Parameters - Activated Partial Thromboplastin Time (aPTT)

    Time frame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

    Maximum change in aPTT from pre-dose

  13. Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Peak

    Time frame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

    Maximum change in TGT parameter from pre-dose

  14. Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Lag and TGT-Time to Peak

    Time frame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

    Maximum change in TGT parameters from pre-dose

  15. Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Endogenous Thrombin Potential

    Time frame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

    Maximum change in TGT parameter from pre-dose

  16. Change in Thrombogenicity Parameter - Fibrinogen

    Time frame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

    Maximum change in thrombogenicity parameter from pre-dose

  17. Change in Thrombogenicity Parameter - Prothrombin Fragments 1 + 2

    Time frame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

    Maximum change in thrombogenicity parameter from pre-dose

  18. Change in Thrombogenicity Parameter - Thrombin/Antithrombin

    Time frame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

    Maximum change in thrombogenicity parameter from pre-dose

  19. Change in Thrombogenicity Parameter - D-Dimer

    Time frame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).

    Maximum change in thrombogenicity parameter from pre-dose

  20. Occurrence of an Antibody Response to MarzAA

    Time frame: From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to End of Study. Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing.

    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

  21. Occurrence of Clinical Thrombotic Event

    Time frame: From the date of first dose of MarzAA until date of first occurrence of clinical event, assessed up to End of Study. Dosing period for each stage was approximately 3 days, with a maximum of approximately 8 weeks of dosing.

    Occurrence of clinical thrombotic event not attributable to another cause

Sponsors and collaborators

Lead sponsor

Catalyst Biosciences

Industry

Registry information

Official study title

Phase 1 Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Ascending Doses of Subcutaneous Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Aug 28, 2019
Registry last updated
Sep 13, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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