Marzeptacog alfa (activated) (MarzAA), a novel activated recombinant Factor VII (rFVIIa) variant, is being developed by Catalyst Biosciences to address the unmet need in haemophilia and other bleeding disorders. MedDRA version: 20.0 Level: LLT Classification code 10066439 Term: Hemophilia System Organ Class: 100000004850
Conditions
Sponsors
Catalyst Biosciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Confirmed diagnosis of congenital Haemophilia A or B with inhibitors with one of the following: a) Titer of =5BU b) Titer of =0.6 BU but expected to have a high anamnestic response to FVIII or FIX, as demonstrated from the subject’s medical history, precluding the use of FVIII or FIX products to treat bleeding as documented by the Investigator c) Titer =0.6 BU but expected to be refractory to increased dosing of FVIII or FIX, as demonstrated from the subject’s medical history, precluding the use of FVIII or FIX products to treat bleeding as documented by the Investigator Note: Documentation of highest historic titer should be recorded. 2) History of bleeding with a historic ABR of =8 3) Male or Female, Age =12 years of age 4) Agreement to use highly effective birth control throughout the study if the subject has childbearing potential 5) If female the subject must meet the following criteria: a) Not currently be breastfeeding b) Not plan on becoming pregnant during the study c) Be surgically sterile, or at least 2-years postmenopausal, or have a negative serum pregnancy test at Screening (Visit 1) 6) Affirmation of informed consent with signature confirmation and assent for children between ages 12 to 17 before any study-related activities Note: study-related activities are any procedure that would not have been performed during normal clinical management of the subject 7) Stated willingness to comply with all study procedures and availability for the duration of the study 8) Investigator confirmed subject’s ability to rapidly assess a bleeding episode and respond appropriately 9) Investigator confirmed subjects’ ability to administer MarzAA SC and infuse standard of care at home Are the trial subjects under 18? yes Number of subjects for this age range: 28 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Previous participation in a study involving SC administration of rFVIIa (NovoSeven or MOD-5014) or any study using a modified amino-acid sequence FVIIa (other than MarzAA) such as: NN1731 or BAY86-6150. Prior participation in a study of IV LR769, rFVIIa-FP (CSL689), or MarzAA is permissible. 2) Previous participation in a clinical study with subsequent treatment within the previous 30 days or =5-half-lives or absence of clinical effect, whichever is longer 3) Known positive antibody to FVIIa or variants thereof wt-rFVIIa detected during screening and prior to Day 1 4) Known hypersensitivity to pd-FVIIa, pd-FVII, wt-rFVIIa or MarzAA or any of the excipients or related products 5) Treatment with anticoagulants or antiplatelet therapy within one week of enrolment or anticipated need during the study 6) Planned elective surgery within 12 months following study entry 7) History of other clinically relevant coagulation disorders 8) Platelet count 35 µmol/L) unless there is a known history of Gilbert’s syndrome c) Serum creatinine (Cr) level >1.25 × ULN 12) Inability or medical, psychosocial, or familial issues that might prevent full participation and cooperation with the procedures and requirements of the clinical study as determined by the potential subject and physician/Investigator 13) Weight =105 kg (231 lbs)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of MarzAA for the on-demand treatment and control of bleeding episodes at 24 hours after the initial dose;Secondary Objective: • To determine the time needed to achieve haemostasis after the initial dose • To assess the ability of MarzAA to achieve and maintain haemostasis in the treatment of bleeds at fixed timepoints after the initial dose • To assess the number of doses and the cumulative dose needed to achieve adequate haemostasis for individual bleeds • To assess the percentage of bleeds with treatment success at 24 hours that maintain haemostatic efficacy at 48 hours after the initial dose • To assess the use and amount of rescue therapy required • To assess the subcutaneous population PK of MarzAA;Primary end point(s): Percentage of bleed treatments resulting in effective (Excellent or Good) hemostasis at 24 hours after the initial dose;Timepoint(s) of evaluation of this end point: 24 hours after dosing | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The time to cessation of bleeding after the initial dose • Percentage of bleed treatment resulting in effective haemostasis at the timepoints (Hours 1, 3, 6, 9, 12, and 48) after the initial dose • Number of doses and cumulative dose needed to achieve haemostasis for individual bleeds • Percentage of bleeds with treatment success at 24 hours that maintain haemostatic efficacy at 48 hours after the initial dose • Use and amount of rescue therapy needed • Population pharmacokinetics of MarzAA ;Timepoint(s) of evaluation of this end point: Percentage of bleed treatment resulting in effective haemostasis at the timepoints (Hours 1, 3, 6, 9, 12, and 48) after the initial dose; Percentage of bleeds with treatment success at 24 hours that maintain haemostatic efficacy at 48 hours after the initial dose | — |
Countries
Armenia, Bulgaria, Denmark, France, Georgia, Hungary, India, Italy, Malaysia, Mexico, Poland, Russian Federation, South Africa, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactDr. Linda Neuman
Catalyst Biosciences, Inc.
Outcome results
None listed