Hemophilia A
Conditions
Keywords
Hemophilia A, Factor VIII, Prophylaxis, Pediatric
Brief summary
Hemophilia A is an inherited blood disorder in which one protein, Factor VIII, needed to form blood clots is missing or not present in sufficient levels. Hemophilia A causes the clotting process to be slowed and the person experiences bleeds causing serious problems that could lead to disability. The current standard treatment for severe hemophilia A is infusion of FVIII to stop bleeding, or regular scheduled treatment to prevent bleeds from occuring. Due to the short half-life of FVIII, prophylaxis may require treatment as often as every other day. In this trial safety and efficacy of a long-acting recombinant Factor VIII molecule is being evaluated in 50 male subjects, \< 12 years of age, with severe Hemophilia A. These subjects will receive open label treatment with long-acting rFVIII for approximately 6 months (or longer until 50 exposure days) on a regular schedule at least once every 7-days. Doses and dose intervals may be adapted to the subject's clinical need. A second group of patients will receive open label treatment with the same drug for 12 weeks on a regular schedule of 2x/week. Patients will attend the treatment center for routine blood samples and will be required to keep an electronic diary. Subjects will be offered participation in an optional extension study to collect observations for at least an additional 50 exposure days.
Interventions
BIOLOGICALBAY94-9027
Study drug dosing was adjusted to the clinical needs of each subject in the range of 25-60 IU/kg/administration, intravenous infusion, at least 50 EDs and a minimum of at least 6 months
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
No minimum to 12 Years
Healthy volunteers
No
Inclusion criteria
* Males \< 12 years of age * Subjects with severe hemophilia A * Previously treated with FVIII for \> 50 exposure days
Exclusion criteria
* Subjects with current evidence of or history of inhibitors to FVIII * Any other inherited or acquired bleeding disorder * Platelet counts \< 100,000/mm\^3 * Creatinine \> 2x the upper limit of normal * Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) \> 5x the upper limit of normal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized number of all bleeds | At least 50 exposure days (ED) over 6 months, on average 245 days | — |
| Pharmacokinetics profile of BAY94-9027 based on blood concentration over the defined time period | Pre-dose to 72 hours post-dose | Pharmacokinetics profile includes maximum concentration (Cmax), half-life (t1/2), area under the concentration versus time curve (AUC), mean residence time (MRT), volume of distribution at steady state (Vss), and clearance (CL) |
| Response of acute bleeding events to treatment based on a 4-point scale (poor, moderate, good, or excellent) | At least 50 exposure days (ED) over 6 months, on average 245 days | — |
| Characterization of a potential immune response | 12 weeks | — |
| Inhibitor development in the extension study | At least 50 additional EDs to achieve at least 100 cumulative EDs, on average 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Inhibitor development in the main study | After 10 to 15 and 50 exposure days (ED) over 6 months, on average 245 days |
| Assessment of incremental recovery in main study | At least 50 exposure days (ED) over 6 months, on average 245 days |
| Number of participants with adverse events as a measure of safety and tolerability | From the start of study treatment up to 7 days after the last dose (Main study: on average 245+7 days; Part 2: 12 weeks+7 days; Extension study: on average 5 years+7 days) |
Countries
Argentina, Austria, Belgium, Bulgaria, Canada, Greece, Israel, Italy, Lithuania, Netherlands, New Zealand, Norway, Poland, Romania, Spain, United Kingdom, United States
Outcome results
None listed