Study to evaluate the efficacy and safety of MarzAA for the control of bleeding episodes in subjects with Haemophilia A or Haemophilia B, with Inhibitors
- Conditions
- 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: 20.0Level: LLTClassification code 10066439Term: HemophiliaSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2020-000996-19-IT
- Lead Sponsor
- Catalyst Biosciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
1)Confirmed diagnosis of congenital HA or HB, with inhibitors, with confirmation of 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 an ABR of =8
3)Male or Female, =12 years of age
4)Agreement to use highly effective birth control throughout the study if the subject has childbearing potential
5)If female, then 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 years 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 subject’s ability to administer MarzAA SC and infuse SOC at home
Are the trial subjects under 18? yes
Number of subjects for this age range:
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
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 intravenous (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 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 enrollment or anticipated need during the study
6)Planned elective surgery within 12 months following study entry
7)History of other clinically relevant coagulation disorder(s)
8)Platelet count <50,000 /µL based on screening laboratory assessments
9)Current or history of advanced atherosclerotic disease (ie, known history of coronary artery disease [CAD], ischemic stroke, etc.), or deep venous thrombosis (DVT) or pulmonary emobolism (PE) within 24 months of dosing or considered to be at a high risk of venous thromboembolic event (VTE) as judged by the Investigator
10)CD 4 T Cell count of <200 cells/ mm3
11)Compromised hepatic or renal function:
a)Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels =5 × the upper limit of normal (ULN)
b)Total bilirubin (TBIL) level =2 mg/dL (>35 µmol/L) unless there is a known history of Gilbert’s syndrome (GS)
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 Investigator
13)Weight =105 kg (231 lbs.)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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<br>• To assess the ability of MarzAA to achieve and maintain haemostasis in the treatment of bleeds at fixed timepoints after the initial dose<br>• To assess the number of doses and the cumulative dose needed to achieve adequate haemostasis for individual bleeds<br>• To assess the percentage of bleeds with treatment success at 24 hours that maintain haemostatic efficacy at 48 hours after the initial dose<br>• To assess the use and amount of rescue therapy required<br>• 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 Outcome Measures
Name Time Method Secondary end point(s): •Time to cessation of bleeding after the initial dose<br>•Percentage of treated bleeding episodes resulting in effective hemostasis at the timepoints (Hours 1, 3 6, 9, 12, and 48) after the initial dose <br>•Number of doses and cumulative dose needed to achieve hemostasis for individual bleeds <br>•Percentage of bleeds with treatment success at 24 hours that maintain hemostatic response at 48 hours after the initial dose<br>•Use and amount of rescue therapy needed <br>•Population pharmacokinetics of subcutaneous 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;<br>Percentage of bleeds with treatment success at 24 hours that maintain haemostatic efficacy at 48 hours after the initial dose