E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
|
E.1.1.1 | Medical condition in easily understood language |
Haemophilia and other bleeding disorders |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066439 |
E.1.2 | Term | Hemophilia |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of MarzAA for the on-demand treatment and control of bleeding episodes at 24 hours after the initial dose |
|
E.2.2 | Secondary objectives of the trial |
• 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 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
|
E.4 | Principal 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 <50,000 /μL based on screening laboratory assessments 9) Current or history of advanced atherosclerotic disease (i.e., known history of coronary artery disease, ischemic stroke, etc.), or deep venous thrombosis (DVT) or pulmonary embolism (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) CD4 T Cell count <200 cells/mm3 11) Compromised hepatic or renal function: a) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≥5 x the upper limit of normal (ULN) b) Total bilirubin level ≥2 mg/dL (>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) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of bleed treatments resulting in effective (Excellent or Good) hemostasis at 24 hours after the initial dose |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | 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
|
|
E.5.2.1 | 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
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Armenia |
Georgia |
India |
Malaysia |
Mexico |
Russian Federation |
South Africa |
Taiwan |
Turkey |
Ukraine |
United States |
Bulgaria |
Denmark |
France |
Hungary |
Italy |
Poland |
Spain |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
For subjects: A subject is considered to have completed the study if all assessments are completed including end of study visit. For the study: when ≥244 bleeds have been treated with MarzAA (cumulative from both sequences) and ≥244 bleeds have been treated with SOC (cumulative from both sequences) and ≥80% of subjects have ≥3 eligible treated bleeds.
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 23 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 23 |