Hemophilia A
Conditions
Keywords
Hemophilia A, Children
Brief summary
The objective of this study is to assess the efficacy and safety of a Von Willebrand Factor/Factor VIII (VWF/FVIII), Biostate, and to investigate the pharmacokinetics of Biostate in children with haemophilia A.
Interventions
BIOLOGICALBiostate
1 dose of 50 IU FVIII/kg body weight of Biostate administered intravenously on Day 1 in the PK component, followed by the Efficacy component for continuation of Biostate therapy, as required for a minimum of 50 exposure days.
Sponsors
Parexel
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
No minimum to 12 Years
Healthy volunteers
No
Inclusion criteria
* Male subjects between 0 and \<12 years of age. * Diagnosed with severe haemophilia A (FVIII:C \<1%), and pre-treated for a minimum of 20 to 50 exposure days. * Have evidence of vaccination against hepatitis A and B (or presence of antibodies against hepatitis A and B due to either a previous infection or prior immunisation), as documented in the medical notes at enrolment. * The subject and/or legal guardian understand(s) the nature of the study and has/have given written informed consent to participate in the study and is/are willing to comply with the protocol.
Exclusion criteria
* For all subjects at Day 1: Are actively bleeding. * Have received an infusion of any FVIII product, cryoprecipitate, whole blood, plasma or desmopressin acetate in the 4 days prior to their dosing within the PK component. * Have a known history of, or who are suspected of having FVIII inhibitors. * Have received aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) within 7 days of administration of the IMP. * Have an impaired liver function ie, bilirubin \>1.5 x upper limit of normal (ULN) and/or aspartate/alanine aminotransferase (AST/ALT) \>2.5 x ULN (referring to limits of the laboratory that performs the determination) at Screening. * Are human immunodeficiency virus \[HIV\]-1/-2 antibody positive with a viral load of \>200/µL. * Suffer from an acute or chronic medical condition, other than haemophilia A, which may, in the opinion of the Investigator, affect the conduct of the study. * Suffering from von Willebrand disease (VWD) with von Willebrand factor: ristocetin cofactor (VWF:RCo) level \<50 IU/dL at Screening. * Have a known or suspected hypersensitivity or previous evidence of severe side effects to a plasma-derived FVIII product or to human albumin. * Have participated in a clinical study or used an investigational compound in another study (eg, a new chemical entity not registered for clinical use) in the 3 months preceding the first day of IMP administration, or are planning to enter such a study during the study period. * Unwillingness and/or inability to comply with the study requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose (IU/kg) per year | 1 year |
| Total clearance of the drug from the body (CL=dose/AUC) of FVIII | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 |
| Number of infusions per bleeding event | 1 day |
| Number of infusions per month | 1 month |
| Number of infusions per year | 1 year |
| Dose (IU/kg) per bleeding event | 1 day |
| Dose (IU/kg) per month | 1 month |
| Subjective assessment of Haemostatic efficacy | Over minimum of 50 exposure days |
| Incremental recovery of FVIII | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 |
| Half-life of FVIII | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 |
| Area under the concentration curve (AUC) of FVIII | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 |
| Mean residence time (MRT) of FVIII | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 |
| Volume of distribution at steady state (Vss) of FVIII | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 |
| Maximum Plasma Concentration (Cmax) of FVIII | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 |
| Minimum Plasma Concentration (Cmin) of FVIII | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 |
| Time the maximum concentration occurs (tmax) of FVIII | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 |
Secondary
| Measure | Time frame |
|---|---|
| Severity of AEs per subject | 6 months |
| Severity of AEs per infusion | 6 months |
| Relatedness of AEs per subject | 6 months |
| Relatedness of AEs per infusion | 6 months |
| Development of FVIII inhibitors | Samples taken at screening visit, on day 2, on months 1 and 3, and at final visit |
| Frequency of adverse events (AEs) | 6 months |
Countries
Belarus, Georgia, Guatemala, Lebanon, Mexico, Ukraine
Outcome results
None listed