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

Hemophilia A Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04072237
• Other study ID #: MAA-102
• Status: Completed
• Phase: Phase 1
• Start date: September 24, 2019
• Est. completion date: June 17, 2020

Study information

• Verified date: September 2021
• Source: Catalyst Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: June 17, 2020
• Est. primary completion date: April 30, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia A With Inhibitor
• Hemophilia A Without Inhibitor
• Hemophilia B
• Hemophilia B With Inhibitor
• Hemophilia B Without Inhibitor

Intervention

Biological:
• MarzAA (marzeptacog alfa [activated])
Single intravenous dose and ascending doses of subcutaneous injection of MarzAA (Coagulation Faction VIIa Variant)

Locations

Country	Name	City	State
Bulgaria	Medical Center "Hippocrates - N"	Plovdiv
Bulgaria	Specialized Hospital for Active Treatment of Hematological Diseases	Sofia
Russian Federation	Kirov Research Institute of Hematology and Blood Transfusion	Kirov
Russian Federation	National Medical Hematology Research Center	Moscow
Russian Federation	Municipal Policlinic # 37, City Center for Hemophilia Treatment	Saint Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
Catalyst Biosciences

Countries where clinical trial is conducted

Bulgaria,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparative MarzAA Activity by Dose Level/Stage - AUC0-8 and AUC0-last	Comparative pharmacokinetics (PK) by dose level/stage based on examination of AUC frequencies of these for each of the dose groups	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.
Primary	Comparative MarzAA Activity by Dose Level/Stage - AUCT1-T2 Normalized by Dose = AUC0-last/Dose	Comparative pharmacokinetics by dose level/stage based on examination of AUC frequency of these for each of the dose groups	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.
Secondary	Comparative MarzAA Activity of Intravenous and Subcutaneous - Cmax	Change in Cmax at each stage for each dose group	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.
Secondary	Comparative MarzAA Activity of Intravenous and Subcutaneous - Tmax	Change in Tmax at each stage for each dose group	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.
Secondary	Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2eqa	Change in T1/2eqa at each stage for each dose group	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.
Secondary	Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2?-z	Change in T1/2?-z at each stage for each dose group	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.
Secondary	Comparative MarzAA Activity of Intravenous and Subcutaneous - CL	Change in CL at each stage for each dose group	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.
Secondary	Comparative MarzAA Activity of Intravenous and Subcutaneous - Vd1	Change in Vd1 at each stage for each dose group	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.
Secondary	Comparative MarzAA Activity of Intravenous and Subcutaneous - BAabs	Change in BAabs at each stage for each dose group	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.
Secondary	Comparative MarzAA Activity of Intravenous and Subcutaneous - Mean Residence Time	Change in Mean Residence Time at each stage for each dose group	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.
Secondary	Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC From T1 to T2 Norm by Dose	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)	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.
Secondary	Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC Infinity Obs and AUC to Last Nonzero Conc	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)	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.
Secondary	Change in Coagulation Parameters - Prothrombin Time (PT)	Maximum change in PT from pre-dose	From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-7 (SC).
Secondary	Change in Coagulation Parameters - Activated Partial Thromboplastin Time (aPTT)	Maximum change in aPTT from pre-dose	From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Secondary	Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Peak	Maximum change in TGT parameter from pre-dose	From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Secondary	Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Lag and TGT-Time to Peak	Maximum change in TGT parameters from pre-dose	From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Secondary	Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Endogenous Thrombin Potential	Maximum change in TGT parameter from pre-dose	From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Secondary	Change in Thrombogenicity Parameter - Fibrinogen	Maximum change in thrombogenicity parameter from pre-dose	From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Secondary	Change in Thrombogenicity Parameter - Prothrombin Fragments 1 + 2	Maximum change in thrombogenicity parameter from pre-dose	From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Secondary	Change in Thrombogenicity Parameter - Thrombin/Antithrombin	Maximum change in thrombogenicity parameter from pre-dose	From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Secondary	Change in Thrombogenicity Parameter - D-Dimer	Maximum change in thrombogenicity parameter from pre-dose	From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
Secondary	Occurrence of an Antibody Response to MarzAA	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	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.
Secondary	Occurrence of Clinical Thrombotic Event	Occurrence of clinical thrombotic event not attributable to another cause	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.