Von Willebrand Disease
Conditions
Keywords
Von Willebrand Disease
Brief summary
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.
Interventions
BIOLOGICALBiostate
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.
Sponsors
Parexel
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
Belarus, Georgia, Germany, Guatemala, Lebanon, Ukraine
Outcome results
None listed