To assess the Pharmacokinetic and Pharmacodynamic properties of three dosages of Coagulation Factor VIIa (Recombinant) in congenital hemophilia A or B patientsTo assess the safety of three dosages of Coagulation factor VIIa (Recombinant) in…
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
- Blood and lymphatic system disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
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.
Background summary
Factor VIIa is a good therapeutic option to treat patients suffering from
haemophilia who have developed antibodies against factor VIII or IX.
GTC aims with this new human recombinant factor VIIA to develop a good therapy
to treat patients with haemophilia.
Study objective
To assess the Pharmacokinetic and Pharmacodynamic properties of three dosages
of Coagulation Factor VIIa (Recombinant) in congenital hemophilia A or B
patients
To assess the safety of three dosages of Coagulation factor VIIa (Recombinant)
in congenital hemophilia A or B patients
Study design
A total of 15 adult male patients with hemophilia A or B (with or without
inhibitors) will receive two administrations of rhFVIIa.
The first Cohort will consist of 10 patients who all receive a low dose. After
evaluation of the safety data and some of the coagulation data up to the 24-36
hours visit by the Data Monitoring Committee, Cohort 2 will be initiated.
Patients in Cohort 2 will be treated with a mid dose. Cohort 2 will consist of
5 patients that were treated in Cohort 1, and 5 newly enrolled patients. After
evaluation of the safety data and some of the coagulation data up to the 24-36
hours visit by the Data Monitoring Committee, Cohort 3 will be initiated.
Patients in Cohort 2 will be treated with a high dose. Cohort 3 will consist of
the 5 patients that were treated in Cohort 1 but not in Cohort 2, and the 5
patients that were newly enrolled in Cohort 2. This design will result in
having 10 patients treated for each dose and all patients having two
administrations at two different dose levels.
Intervention
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).
Study burden and risks
The study day is intensive as a consequence of the relatively frequent blood
sampling. The insertion of a canule can be painful and result in a bruise.
There is a potential risk for disturbance of coagulation, but the risks for the
volunteers are small, because they have a bleeding tendency.
Crossing Boulevard 175
Framingham MA 01702
US
Crossing Boulevard 175
Framingham MA 01702
US
Listed location countries
Age
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-002285-13-NL |
| CCMO | NL41575.058.12 |