Clinical trial NCT00879541: Study of a pd vWF/FVIII, Biostate®, in Subjects With Haemophilia A
Official title: A Phase II, Multicentre, Double-blinded, Randomised, Cross-over Study to Evaluate Efficacy, Safety and Pharmacokinetics of Biostate® in Subjects With Haemophilia A.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemophilia A
Keywords: Hemophilia A
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2009-04-10
Enrollment: 81
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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® \[SP\].


Eligibility criteria: 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

Primary outcomes:
measure: Haemostatic efficacy
timeFrame: Monthly, until final study visit
measure: Number of treatments/units required to resolve any bleeding event
timeFrame: From Day 1 until final study visit
measure: FVIII concentrate usage (number of infusions, IU/kg per event, per month, and per year)
timeFrame: From Day 1 until final study visit
measure: Assessment of blood loss during any surgical procedure
timeFrame: From Day 1 until final study visit
measure: Pharmacokinetics of FVIII activity
timeFrame: Up to 48 hours following infusions (Part 1 and Part 3 only)
Secondary outcomes:
measure: The nature, frequency and incidence of adverse events
timeFrame: From Day 1 until final study visit
measure: Development of FVIII inhibitors
timeFrame: From Day 1 until final study visit
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
facility: Study Site
city: Sofia
country: Bulgaria
facility: Study Site
city: Varna
country: Bulgaria
facility: Study Site
city: Skopje
country: Macedonia, The Former Yugoslav Republic of
facility: Study Site
city: Bialystok
country: Poland
facility: Study Site
city: Gdansk
country: Poland
facility: Study Site
city: Krakow
country: Poland
facility: Study Site
city: Lublin
country: Poland
facility: Study Site
city: Poznan
country: Poland
facility: Study Site
city: Warszawa
country: Poland
facility: Study Site
city: Wroclaw
country: Poland
facility: Study Site
city: Barnaul
country: Russian Federation
facility: Study Site
city: Kirov
country: Russian Federation
facility: Study Site
city: Moscow
country: Russian Federation
facility: Study Site
Study officials:
References: