Study of Biostate® in Children With Von Willebrand Disease

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

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.

Study Overview

• Status: Completed
• Conditions: Von Willebrand Disease
• Intervention / Treatment: Biological: Biostate

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Homel, Belarus, 246040
    • Study Site
  • Minsk, Belarus, 223040
    • Study Site
• Georgia
  • Tbilisi, Georgia, 0179
    • Study Site
• Germany
  • Bremen, Germany, 28177
    • Study Site
• Guatemala
  • CP
    • Guatemala, CP, Guatemala, 01010
      • Study Site
• Lebanon
  • Beirut, Lebanon
    • Study Site
• Ukraine
  • Lviv, Ukraine
    • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biostate	Biological: Biostate; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Half-life 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
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
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
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	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

Collaborators and Investigators

• Sponsor: CSL Behring
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: October 1, 2010
• First Submitted That Met QC Criteria: October 1, 2010
• First Posted (Estimate): October 4, 2010

Study Record Updates

• Last Update Posted (Actual): October 3, 2017
• Last Update Submitted That Met QC Criteria: October 2, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Von Willebrand Disease
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Blood Platelet Disorders; Von Willebrand Diseases
• Other Study ID Numbers: CSLCT-BIO-08-52; 1494 (CSL Behring); 2009-017753-34 (EudraCT Number)