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

Catalyst Biosciences5 sites in 2 countries11 target enrollmentSeptember 24, 2019

ConditionsHemophilia A Hemophilia B Hemophilia A With Inhibitor Hemophilia B With Inhibitor Hemophilia A Without Inhibitor Hemophilia B Without Inhibitor

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Hemophilia A
Sponsor: Catalyst Biosciences
Enrollment: 11
Locations: 5
Primary Endpoint: Comparative MarzAA Activity by Dose Level/Stage - AUC0-∞ and AUC0-last
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

Detailed 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).

Registry

clinicaltrials.gov

Start Date

September 24, 2019

End Date

June 17, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Sequential

Sex

Male

Investigators

Sponsor

Catalyst Biosciences

Responsible Party

Sponsor

Eligibility Criteria

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

Outcomes

Primary Outcomes

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

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

Secondary Outcomes

Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC From T1 to T2 Norm by Dose(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.)
Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC Infinity Obs and AUC to Last Nonzero Conc(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 MarzAA Activity of Intravenous and Subcutaneous - T1/2eqα(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 MarzAA Activity of Intravenous and Subcutaneous - Cmax(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 MarzAA Activity of Intravenous and Subcutaneous - Tmax(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 MarzAA Activity of Intravenous and Subcutaneous - BAabs(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 MarzAA Activity of Intravenous and Subcutaneous - Mean Residence Time(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 Coagulation Parameters - Activated Partial Thromboplastin Time (aPTT)(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Lag and TGT-Time to Peak(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2λ-z(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 MarzAA Activity of Intravenous and Subcutaneous - Vd1(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 MarzAA Activity of Intravenous and Subcutaneous - CL(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 Thrombogenicity Parameter - Fibrinogen(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
Change in Thrombogenicity Parameter - Prothrombin Fragments 1 + 2(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
Change in Thrombogenicity Parameter - Thrombin/Antithrombin(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
Occurrence of an Antibody Response to MarzAA(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.)
Change in Coagulation Parameters - Prothrombin Time (PT)(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-7 (SC).)
Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Peak(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Endogenous Thrombin Potential(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
Change in Thrombogenicity Parameter - D-Dimer(From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).)
Occurrence of Clinical Thrombotic Event(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.)