Haemophilia
Conditions
Interventions
rhFVIIa will be administered at a low, mid and high dose intravenously as a 2-3
minute bolus dose. Each patient will receive two administrations (at a
different dose level).
Sponsors
GTC Biotherapeutics, Inc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. be male with a diagnosis of moderate or severe congenital hemophilia A and/or B (with or without inhibitors);2. be 18 years or older, up to and including 75 years of age;3. be capable of understanding and willing to comply with the conditions of the protocol;4. have read, understood and provided written informed consent
Exclusion criteria
Exclusion criteria: 1. have any coagulation disorder other than hemophilia A or B;2. have a body weight >105 kg (231 lb);3. be immuno-suppressed (i.e., the patient should not receive systemic immunosuppressive medication 200/µl);4. have a known allergy or hypersensitivity to rabbits ;5. have platelet count 3 times the upper limit of normal) and/or renal impairment (creatinine >2 times the upper limit of normal);11. have a history of arterial and/or venous thromboembolic events (such as myocardial infarction, ischemic strokes, transient ischemic attacks, deep venous thrombosis or pulmonary embolism) within 2 years prior to first dose of study drug, have an arterial stent in place or have clinically significant atherosclerotic disease (e.g., angina pectoris, peripheral vascular disease);12. use any anticoagulant for arterial/venous obstructions and/or atrial fibrillation within 7 daysprior to first study drug administration;13. have an active malignancy (those with non-melanoma skin cancer are allowed);14. have any life-threatening disease or other disease or condition which, according to the investigator*s judgment, could imply a potential hazard to the patient, interfere with the trial participation or trial outcome
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic variables: Terminal half life (t1/2); area-under-the-concentration-versus-time curve from time 0 to the time of the last measurable concentration (AUC0-t); area-under-the-concentration-versus-time curve from time 0 to infinity (AUC0-inf); Mean Residence Time (MRT); Clearance (Cl); Volume of Distribution at steady state (Vss); Maximum Concentration achieved (Cmax); and time at which maximum concentration is achieved (tmax). Pharmacodynamic variables: Thrombin generation assay output (performed at low and high TF, and with added platelets), including lag time, time to peak, peak, and endogenous thrombin potential (ETP); activated partial thromboplastin time (aPTT); prothrombin time (PT). Besides its use in the PK analyses, FVIIa activity is also regarded a PD parameter. | — |
Secondary
| Measure | Time frame |
|---|---|
| Physical examinations, ECGs, vital signs, clinical laboratory tests (serum chemistry, hematology, urinalysis), immunology tests (including storage sample for potential future use), and monitoring of adverse events. Assessment of (anti-)coagulation parameters (above listed PD markers like prothrombin fragments F1+2 (F1+2), D-dimer, and TAT) will be used to assess the safety of the drugs as well. | — |
Countries
Netherlands
Outcome results
None listed