Study of Biostate® in Children With Hemophilia A

Study Overview
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Brief Summary
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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.

Official Title
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A Phase III, Open-Label, Multicentre Study to Evaluate Efficacy, Pharmacokinetics, and Safety of Biostate® in Paediatric Subjects With Haemophilia A

Conditions
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Hemophilia A

Intervention / Treatment
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* Biological: Biostate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 12 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biostate<br> | Biological: Biostate<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Dose (IU/kg) per year |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events (AEs) |  | 6 months | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia A, Children