Clinical trial NCT03407651: Study of Coagulation Factor VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia A and B
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemophilia A With Inhibitor
Hemophilia B With Inhibitor
Lead sponsor: Catalyst Biosciences
Sponsor class: INDUSTRY
First posted: 2018-01-23
Enrollment: 11
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Bleeding Episode Prevention Success
timeFrame: Day 1 of final MarzAA dose level - Day 50
Secondary outcomes:
measure: Occurrence of Breakthrough Bleeding
timeFrame: From Day 5 of dose level until occurrence of event
measure: Occurrence of Clinical Thrombotic Event
timeFrame: From date of first dose until date of first occurrence of clinical event, assessed up to treatment Day 50
measure: Coagulation Assessment - Prothrombin Time
timeFrame: From date of pre-dose to 24 hours (Part 1a), pre-dose to 48 hours (Part 1b), and pre-dose to Day 50 (Part 2)
measure: Coagulation Assessment - Activated Partial Thromboplastin Time
timeFrame: From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), to Day 50/end of study (Part 2)
measure: Coagulation Assessment - Fibrinogen
timeFrame: From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), or Day 50 (Part 2).
measure: Number of Events of Antibody Formation
timeFrame: From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50
measure: Number of Events of an Antibody Response
timeFrame: From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50.
measure: Thrombogenicity Assessment
timeFrame: From time of pre-dose of MarzAA at Day 1 until date of first occurrence of thrombotic event, assessed up to treatment Day 50.
Other outcomes:
Locations:
city: Yerevan
country: Armenia
facility: Hematology Center after Prof. R. Yeolyan
city: Tbilisi
country: Georgia
facility: JSC "K.Eristavi National Center of Experimental and Clinical Surgery"
city: Tbilisi
country: Georgia
facility: LTD M.Zodelava Hematology Centre
city: Tbilisi
country: Georgia
facility: LTD Medinvest - Institute of Hematology and Transfusiology
city: Rzeszów
country: Poland
facility: Gabinet Lekarski, Bartosz Korczowski
city: Kemerovo
country: Russian Federation
facility: Regional Clinical Hospital
city: Kirov
country: Russian Federation
facility: FGU Kirov Scientific Research
city: Saint Petersburg
country: Russian Federation
facility: Center for Hemophilia Treatment
city: Johannesburg
country: South Africa
facility: Haemophilia Comprehensive Care Centre
Study officials:
affiliation: Catalyst Biosciences
name: Howard Levy, MD, PhD, MMM
role: STUDY_DIRECTOR
References: