Study of Coagulation Factor VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia A and B
- Conditions
- Hemophilia B With InhibitorHemophilia A With Inhibitor
- Interventions
- Biological: Coagulation Factor VIIa variant
- Registration Number
- NCT03407651
- Lead Sponsor
- Catalyst Biosciences
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 11
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2 Coagulation Factor VIIa variant Coagulation Factor VIIa variant, 30, 60, 90, 120 µg/kg by subcutaneous route Part 1a Coagulation Factor VIIa variant Coagulation Factor VIIa variant, 18 µg/kg by intravenous route Part 1b Coagulation Factor VIIa variant Coagulation Factor VIIa variant, 30 µg/kg by subcutaneous route
- Primary Outcome Measures
Name Time Method Bleeding Episode Prevention Success Day 1 of final MarzAA dose level - Day 50 Annualized bleed rate (ABR; spontaneous and total) during Part 2 when on final MarzAA dose level versus recorded historical ABR. The analysis of the primary endpoint (annualized bleeding rate ABR for spontaneous and traumatic bleeds) of the final dose of MarzAA each subject was treated was based on the 1-sample test compared to a predefined rate assumed for the on-demand therapy. The latter was assumed to be 12 (or 1 bleed per month), which was the minimum ABR for each subject according to inclusion criterion 2 (defined as the H0), with no maximum value. A higher score indicated a worse outcome. ABR is on a scale of 0 to 365, with a lower score reflective of a lower number of bleeding events in a year.
- Secondary Outcome Measures
Name Time Method Number of Events of Antibody Formation From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50 Occurrence of antibody formation resulting in a decreased endogenous level of coagulation Factor VII (FVII) or Factor VII activated (FVIIa)
Number of Events of an Antibody Response From time of first dose of MarzAA until date of first occurrence of clinical event, assessed up to treatment Day 50. 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.
Occurrence of Breakthrough Bleeding From Day 5 of dose level until occurrence of event Occurrence of breakthrough bleeds requiring escalation to higher dose level
Occurrence of Clinical Thrombotic Event From date of first dose until date of first occurrence of clinical event, assessed up to treatment Day 50 Occurrence of clinical thrombotic event not attributable to another cause
Coagulation Assessment - Prothrombin Time 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) Change in coagulation parameter (prothrombin time \[PT\]) from pre-dose. Min-max values are reflective of the highest and lowest values for all measured timepoints.
Coagulation Assessment - Activated Partial Thromboplastin Time From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), to Day 50/end of study (Part 2) Change in coagulation parameter (activated partial thromboplastin time \[aPTT\]) from pre-dose. Min-max values are reflective of the highest and lowest values for all measured timepoints.
Coagulation Assessment - Fibrinogen From date of pre-dose to 24 hours (Part 1a), 48 hours (Part 1b), or Day 50 (Part 2). Change in coagulation parameter (fibrinogen) from pre-dose. Min-max values are reflective of the highest and lowest values for all measured timepoints.
Thrombogenicity Assessment From time of pre-dose of MarzAA at Day 1 until date of first occurrence of thrombotic event, assessed up to treatment Day 50. Number of participants with clinically significant levels of thrombogenicity markers (D-dimer, Prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin complex \[TAT\]), based on standard laboratory tests and clinical examination with a specific search for any signs of thrombosis
Trial Locations
- Locations (9)
LTD M.Zodelava Hematology Centre
🇬🇪Tbilisi, Georgia
LTD Medinvest - Institute of Hematology and Transfusiology
🇬🇪Tbilisi, Georgia
Haemophilia Comprehensive Care Centre
🇿🇦Johannesburg, South Africa
Regional Clinical Hospital
🇷🇺Kemerovo, Russian Federation
FGU Kirov Scientific Research
🇷🇺Kirov, Russian Federation
Center for Hemophilia Treatment
🇷🇺Saint Petersburg, Russian Federation
JSC "K.Eristavi National Center of Experimental and Clinical Surgery"
🇬🇪Tbilisi, Georgia
Gabinet Lekarski, Bartosz Korczowski
🇵🇱Rzeszów, Poland
Hematology Center after Prof. R. Yeolyan
🇦🇲Yerevan, Armenia