Study of Biostate® in Children With Von Willebrand Disease

Study Overview
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Brief Summary
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This is an open-label study to investigate the pharmacokinetics (PK), efficacy, and safety of a von Willebrand Factor/Factor VIII (VWF/FVIII), Biostate, in children with Von Willebrand disease (VWD) in whom treatment with a VWF product is required for prophylactic therapy, haemostatic control during surgery, or control of a non-surgical, spontaneous, or traumatic bleeding event.

Official Title
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A Phase III Open-label, Multi-centre Study to Assess the Pharmacokinetics, Efficacy, and Safety of Biostate® in Paediatric Subjects With Von Willebrand Disease

Conditions
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Von Willebrand Disease

Intervention / Treatment
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* Biological: Biostate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects between 0 and <12 years of age Diagnosed with VWD Type 1, 2A, or 3 Desmopressin acetate (DDAVP) treatment is ineffective, contraindicated, or not available for subject von Willebrand factor: ristocetin cofactor (VWF:RCo) is <20% at screening or the subject has a history of VWF:RCo <10% 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 immunization Written informed consent given Exclusion Criteria: Active bleeding immediately prior to initial PK period Received treatment with DDAVP or a VWF concentrate product for their VWD in the 5 days prior to their first study treatment Have received aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) within 7 days of commencing the PK period. Known history or suspicion of having VWF or FVIII inhibitors Acute or chronic medical condition, other than VWD, which may affect the conduct of the study Known or suspected hypersensitivity or previous evidence of severe side effects to other FVIII/VWF concentrates Participation in a clinical study or use of an investigational compound in another study in the 3 months preceding study start 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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All

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>* PK component: Single bolus infusion of 80 IU VWF:RCo/kg administered intravenously on Day 1, and approximately Day 180 in Type 3 VWD subjects only. Efficacy component: Repeated bolus doses over 12 months as required to manage VWD condition.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemostatic efficacy |  | From Day 1 until final study visit | 
| Incremental Recovery of VWF |  | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 and 6 months after initial dose | 
| 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 VWF |  | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 and 6 months after initial dose | 
| 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 VWF |  | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 and 6 months after initial dose | 
| AUC 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 VWF |  | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 and 6 months after initial dose | 
| 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 VWF |  | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 and 6 months after initial dose | 
| 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 to maximum concentration (tmax) of VWF |  | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 and 6 months after initial dose | 
| Time to maximum concentration (tmax) 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 VWF |  | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 and 6 months after initial dose | 
| 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 | 
| Clearance (CL) of VWF |  | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 and 6 months after initial dose | 
| Clearance (CL) of FVIII |  | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 | 
| Volume of distribution of steady state (Vss) of VWF |  | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 and 6 months after initial dose | 
| Volume of distribution of steady state (Vss) of FVIII |  | Samples taken prior and then 0.5, 4, 8, 24, and 48 h after the infusion on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events (AEs) per infusion |  | 13 months | 
| Severity of AEs per infusion |  | 13 months | 
| Severity of AEs per subject |  | 13 months | 
| Relatedness of AEs per infusion |  | 13 months | 
| Relatedness of AEs per subject |  | 13 months | 
| Development of VWF inhibitors |  | Sample taken at baseline, then every 3 months up to 12 months | 
| Development of FVIII inhibitors |  | Sample taken at baseline, then every 3 months up to 12 months | 
| Frequency of adverse events (AEs) per subject |  | 13 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Von Willebrand Disease