Clinical trial NCT01229007: Study of Biostate® in Children With Hemophilia A
Official title: A Phase III, Open-Label, Multicentre Study to Evaluate Efficacy, Pharmacokinetics, and Safety of Biostate® in Paediatric Subjects With Haemophilia A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A
Keywords: Hemophilia A
Children
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2010-10-27
Enrollment: 35
Sex: MALE
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Subjective assessment of Haemostatic efficacy
timeFrame: Over minimum of 50 exposure days
measure: Incremental recovery of FVIII
timeFrame: Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1
measure: Half-life of FVIII
timeFrame: Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1
measure: Area under the concentration curve (AUC) of FVIII
timeFrame: Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1
measure: Mean residence time (MRT) of FVIII
timeFrame: Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1
measure: Volume of distribution at steady state (Vss) of FVIII
timeFrame: Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1
measure: Maximum Plasma Concentration (Cmax) of FVIII
timeFrame: Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1
measure: Minimum Plasma Concentration (Cmin) of FVIII
timeFrame: Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1
measure: Time the maximum concentration occurs (tmax) of FVIII
timeFrame: Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1
measure: Total clearance of the drug from the body (CL=dose/AUC) of FVIII
timeFrame: Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1
measure: Number of infusions per bleeding event
timeFrame: 1 day
measure: Number of infusions per month
timeFrame: 1 month
measure: Number of infusions per year
timeFrame: 1 year
measure: Dose (IU/kg) per bleeding event
timeFrame: 1 day
measure: Dose (IU/kg) per month
timeFrame: 1 month
measure: Dose (IU/kg) per year
timeFrame: 1 year
Secondary outcomes:
measure: Frequency of adverse events (AEs)
timeFrame: 6 months
measure: Severity of AEs per subject
timeFrame: 6 months
measure: Severity of AEs per infusion
timeFrame: 6 months
measure: Relatedness of AEs per subject
timeFrame: 6 months
measure: Relatedness of AEs per infusion
timeFrame: 6 months
measure: Development of FVIII inhibitors
timeFrame: Samples taken at screening visit, on day 2, on months 1 and 3, and at final visit
Other outcomes:
Locations:
city: Gomel
country: Belarus
facility: Study site
city: Minsk
country: Belarus
facility: Study site
city: Tbilisi
country: Georgia
facility: Study Site
city: Guatemala
country: Guatemala
facility: Study Site
city: Beirut
country: Lebanon
facility: Study Site
city: Monterrey
country: Mexico
facility: Study site
city: Dnipropetrovsk
country: Ukraine
facility: Study Site
city: Lviv
country: Ukraine
facility: Study Site
Study officials:
affiliation: CSL Behring
name: Program Director Clinical R&D
role: STUDY_DIRECTOR
References: