Study of Biostate® in Children With Hemophilia A

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

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia A
• Intervention / Treatment: Biological: Biostate

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Gomel, Belarus, 246040
    • Study Site
  • Minsk, Belarus, 223040
    • Study Site
• Georgia
  • Tbilisi, Georgia, 0179
    • Study Site
• Guatemala
  • Guatemala, Guatemala, 01010
    • Study Site
• Lebanon
  • Beirut, Lebanon
    • Study Site
• Mexico
  • Monterrey, Mexico, 64000
    • Study Site
• Ukraine
  • Dnipropetrovsk, Ukraine
    • Study Site
  • 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: Male

Description

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.

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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: CSL Behring
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: October 1, 2010
• First Submitted That Met QC Criteria: October 26, 2010
• First Posted (Estimate): October 27, 2010

Study Record Updates

• Last Update Posted (Actual): August 24, 2017
• Last Update Submitted That Met QC Criteria: August 23, 2017
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Children; Hemophilia A
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: CSLCT-BIO-08-53; 1495 (Recep Tayyip Erdogan University, Department of Scientific Research Project); 2009-015112-18 (EudraCT Number)