Study of a pd vWF/FVIII, Biostate®, in Subjects With Haemophilia A

A Phase II, Multicentre, Double-blinded, Randomised, Cross-over Study to Evaluate Efficacy, Safety and Pharmacokinetics of Biostate® in Subjects With Haemophilia A.

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].

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