A Phase Ib, Dose Escalation Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Patients

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 9

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

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 <30 days prior to enrollment, CD4 counts at screening should be >200/µl);4. have a known allergy or hypersensitivity to rabbits ;5. have platelet count <100,000/mL;6. have had within one month prior to first administration of the study drug in this study a major surgical procedure (e.g. orthopedic, abdominal);7. have an active, ongoing bleeding for which the patient is being treated, or treatment for a bleeding was stopped within 24 hours of the time of study drug administration;8. have received a Factor VII or FVIIa containing product (either plasma derived or recombinant) within 72 hours prior to any study drug administration;9. have received an investigational drug within 30 days of the first study drug administration, or is expected to receive such drug during participation in this study;10. have a clinically relevant hepatic (hepatic enzymes >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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Pharmacokinetic variables:<br /><br>Terminal half life (t1/2); area-under-the-concentration-versus-time curve from<br /><br>time 0 to the time of the last measurable concentration (AUC0-t);<br /><br>area-under-the-concentration-versus-time curve from time 0 to infinity<br /><br>(AUC0-inf); Mean Residence Time (MRT); Clearance (Cl); Volume of Distribution<br /><br>at steady state (Vss); Maximum Concentration achieved (Cmax); and time at which<br /><br>maximum concentration is achieved (tmax).<br /><br>Pharmacodynamic variables:<br /><br>Thrombin generation assay output (performed at low and high TF, and with added<br /><br>platelets), including lag time, time to peak, peak, and endogenous thrombin<br /><br>potential (ETP); activated partial thromboplastin time (aPTT); prothrombin time<br /><br>(PT). Besides its use in the PK analyses, FVIIa activity is also regarded a PD<br /><br>parameter.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Physical examinations, ECGs, vital signs, clinical laboratory tests (serum<br /><br>chemistry, hematology, urinalysis), immunology tests (including storage sample<br /><br>for potential future use), and monitoring of adverse events.<br /><br>Assessment of (anti-)coagulation parameters (above listed PD markers like<br /><br>prothrombin fragments F1+2 (F1+2), D-dimer, and TAT) will be used to assess the<br /><br>safety of the drugs as well.</p><br>