Study of a Plasma-Derived Von Willebrand Factor/Factor VIII Concentrate (vWF/FVIII), Biostate®, in Subjects With Haemophilia A


Tracking Information

Start Date  ICMJEFebruary 2009
Estimated Primary Completion DateJuly 2010   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE 
 (submitted: April 9, 2009)
  • Haemostatic efficacy [ Time Frame: Monthly, until final study visit ] [ Designated as safety issue: No ]
  • Number of treatments/units required to resolve any bleeding event [ Time Frame: From Day 1 until final study visit ] [ Designated as safety issue: No ]
  • FVIII concentrate usage (number of infusions, IU/kg per event, per month, and per year) [ Time Frame: From Day 1 until final study visit ] [ Designated as safety issue: No ]
  • Assessment of blood loss during any surgical procedure [ Time Frame: From Day 1 until final study visit ] [ Designated as safety issue: No ]
  • Pharmacokinetics of FVIII activity [ Time Frame: Up to 48 hours following infusions (Part 1 and Part 3 only) ] [ Designated as safety issue: No ]
Original Primary Outcome Measures  ICMJESame as current
Change HistoryComplete list of historical versions of study NCT00879541 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE 
 (submitted: April 9, 2009)
  • The nature, frequency and incidence of adverse events [ Time Frame: From Day 1 until final study visit ] [ Designated as safety issue: Yes ]
  • Development of FVIII inhibitors [ Time Frame: From Day 1 until final study visit ] [ Designated as safety issue: Yes ]
Original Secondary Outcome Measures  ICMJESame as current

Descriptive Information

Brief Title  ICMJEStudy of a Plasma-Derived Von Willebrand Factor/Factor VIII Concentrate (vWF/FVIII), Biostate®, in Subjects With Haemophilia A
Official Title  ICMJEA Phase II, Multicentre, Double-Blinded, Randomised, Cross-Over Study to Evaluate Efficacy, Safety and Pharmacokinetics of Biostate® in Subjects With Haemophilia A.
Brief Summary

The aim of this study are to

  • assess the efficacy of Biostate® [Study Product (SP)] in subjects with Haemophilia A
  • compare the pharmacokinetics of Biostate® [SP] with the previously marketed product Biostate® (here referred to as Biostate® [Reference Product (RP)]).

This study is divided into 3 parts:

Part 1: Cross-over pharmacokinetic (PK) component. PK subjects will be randomised to determine the order in which they receive the two study products. This part of the study is double-blinded.

Part 2: Efficacy component. All subjects will receive Biostate® [SP] as required to manage their haemophilia condition for an estimated period of 6 months (or minimum of 50 exposure days) to assess efficacy and safety of the product. This part of the study is open-label.

Part 3: Repeat pharmacokinetic assessment. Subjects who participated in Part 1 (PK component) will undergo a repeat PK assessment on Day 180 following administration of Biostate® [SP].

Detailed Description 
Study PhasePhase II
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Double Blind (Subject, Investigator), Crossover Assignment, Safety/Efficacy Study
Condition  ICMJEHemophilia A
Intervention  ICMJE
  • Biological: Biostate® [SP]
    Single bolus intravenous dose of 50 IU/kg
    Other Name: Human Coagulation Factor VIII / von Willebrand Factor
  • Biological: Biostate® [SP]
    The dose is dependent on the reason for use and may consist of repeated bolus doses as required to manage haemophilia condition.
    Other Name: Human Coagulation Factor VIII / von Willebrand Factor
  • Biological: Biostate® [RP]
    Single bolus intravenous dose of 50 IU/kg.
    Other Names:
    • Biostate®
    • Human Coagulation Factor VIII / von Willebrand Factor
Study Arms / Comparison Groups
  • PK Biostate® [SP]

    Part 1: PK subjects are randomized to receive Biostate® [SP] either on Day 1 or Day 8.

    Part 3: All PK subjects receive Biostate® [SP] on Day 180.

    Intervention: Biological: Biostate® [SP]
  • PK Biostate® [RP]
    Part 1: PK subjects are randomized to receive Biostate® [RP] either on Day 1 or Day 8.
    Intervention: Biological: Biostate® [RP]
  • Efficacy: Experimental
    Part 2: This arm includes all subjects during the efficacy component of the study.
    Intervention: Biological: Biostate® [SP]

Recruitment Information

Estimated Enrollment  ICMJE62
Estimated Completion DateJuly 2010
Estimated Primary Completion DateJuly 2010   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosed with Haemophilia A with ≤ 1% Factor VIII (FVIII) levels in the absence of factor replacement
  • 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) within 10 years prior to Day 1 documented in the medical notes
  • At least 150 days of prior exposure to a FVIII replacement product
  • Written informed consent given

Exclusion Criteria (for participation in the pharmacokinetic (PK) component):

  • Active bleeding
  • Body weight > 100 kg

Exclusion Criteria (for all subjects):

  • Receipt of an infusion of any FVIII product, cryoprecipitate, whole blood, plasma, or desmopressin acetate (DDAVP) in the 4 days prior to Day 1
  • Known history of FVIII inhibitors, or FVIII inhibitor level > 0.6 Bethesda Units (BU) at screening
  • Receipt of aspirin or other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) within 7 days of administration of study product.
  • CD4 lymphocytes < 200/µL. Subjects wo are HIV-1 positive may be considered for the study if viral load ≤ 200 particles/µL at screening and all other eligibility criteria are met.
  • Impaired liver function ie. bilirubin >1.5 x upper limit of normal (ULN) and/or AST/ALT > 2.5 x ULN at screening.
  • Acute or chronic medical condition, other than haemophilia A, which may, in the opinion of the Investigator, affect the conduct of the study
  • von Willebrand Disease (VWD) with Von Willebrand Factor:Ristocetin Cofactor (vWF:RCo) level < 50 IU/dL at screening
  • Evidence or a history (within the previous 12 months) of abuse of any drug substance, licit or illicit
  • Known or suspected hypersensitivity or previous evidence of severe side effects to Biostate®, FVIII concentrates or human albumin
  • Participation in a clinical study or use of an investigational compound (e.g. a new chemical entity not approved for clinical use) in the 3 months preceding the first day of study drug administration, or plans to enter such a study during the study period
  • Not willing and/or not able to comply with study requirements
GenderMale
Ages12 Years and older
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: Central Contact: Clinical Trial Registration Coordinatorclinicaltrials@cslbehring.com
Location Countries  ICMJEBulgaria,   Poland,   Russian Federation

Administrative Information

NCT ID  ICMJENCT00879541
Responsible PartyGlobal Head Clinical Research & Development, CSL Behring
Study ID Numbers  ICMJE1476, CSLCT-BIO-07-47
Study Sponsor  ICMJECSL Behring
Collaborators  ICMJEParexel
Investigators  ICMJE 
Information Provided ByCSL Behring