Clinical trial NCT04072237: Study of Coagulation Faction VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hemophilia A
Hemophilia B
Hemophilia A With Inhibitor
Hemophilia B With Inhibitor
Hemophilia A Without Inhibitor
Hemophilia B Without Inhibitor
Lead sponsor: Catalyst Biosciences
Sponsor class: INDUSTRY
First posted: 2019-08-28
Enrollment: 11
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: DIAGNOSTIC

Brief 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.

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).

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

Primary outcomes:
measure: Comparative MarzAA Activity by Dose Level/Stage - AUC0-∞ and AUC0-last
timeFrame: 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.
measure: Comparative MarzAA Activity by Dose Level/Stage - AUCT1-T2 Normalized by Dose = AUC0-last/Dose
timeFrame: 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 outcomes:
measure: Comparative MarzAA Activity of Intravenous and Subcutaneous - Cmax
timeFrame: 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.
measure: Comparative MarzAA Activity of Intravenous and Subcutaneous - Tmax
timeFrame: 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.
measure: Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2eqα
timeFrame: 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.
measure: Comparative MarzAA Activity of Intravenous and Subcutaneous - T1/2λ-z
timeFrame: 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.
measure: Comparative MarzAA Activity of Intravenous and Subcutaneous - CL
timeFrame: 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.
measure: Comparative MarzAA Activity of Intravenous and Subcutaneous - Vd1
timeFrame: 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.
measure: Comparative MarzAA Activity of Intravenous and Subcutaneous - BAabs
timeFrame: 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.
measure: Comparative MarzAA Activity of Intravenous and Subcutaneous - Mean Residence Time
timeFrame: 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.
measure: Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC From T1 to T2 Norm by Dose
timeFrame: 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.
measure: Effect of Split Injections on MarzAA Activity by Dose Level/Stage - AUC Infinity Obs and AUC to Last Nonzero Conc
timeFrame: 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.
measure: Change in Coagulation Parameters - Prothrombin Time (PT)
timeFrame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-7 (SC).
measure: Change in Coagulation Parameters - Activated Partial Thromboplastin Time (aPTT)
timeFrame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
measure: Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Peak
timeFrame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
measure: Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Lag and TGT-Time to Peak
timeFrame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
measure: Change in Coagulation Parameters - Thrombin Generation Time (TGT) - TGT-Endogenous Thrombin Potential
timeFrame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
measure: Change in Thrombogenicity Parameter - Fibrinogen
timeFrame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
measure: Change in Thrombogenicity Parameter - Prothrombin Fragments 1 + 2
timeFrame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
measure: Change in Thrombogenicity Parameter - Thrombin/Antithrombin
timeFrame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
measure: Change in Thrombogenicity Parameter - D-Dimer
timeFrame: From predose to Day 2 at stage 1 (IV). From predose to Day 3 at stages 2-9 (SC).
measure: Occurrence of an Antibody Response to MarzAA
timeFrame: 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.
measure: Occurrence of Clinical Thrombotic Event
timeFrame: 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.
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
facility: Medical Center "Hippocrates - N"
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Hematological Diseases
city: Kirov
country: Russian Federation
facility: Kirov Research Institute of Hematology and Blood Transfusion
city: Moscow
country: Russian Federation
facility: National Medical Hematology Research Center
city: Saint Petersburg
country: Russian Federation
facility: Municipal Policlinic # 37, City Center for Hemophilia Treatment
Study officials:
affiliation: Sponsor GmbH
name: Howard Levy, MD, PhD, MMM
role: STUDY_DIRECTOR
References: