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

Study Overview
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Brief Summary
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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].

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

Conditions
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Hemophilia A

Intervention / Treatment
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* Biological: Biostate® [SP]
* Biological: Biostate® [SP]
* Biological: Biostate® [RP]


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: PK Biostate® [SP]<br>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. | Biological: Biostate® [SP]<br>* Single bolus intravenous dose of 50 IU/kg<br>* Other names: Human Coagulation Factor VIII / von Willebrand Factor;|
| Other: PK Biostate® [RP]<br>Part 1: PK subjects are randomized to receive Biostate® [RP] either on Day 1 or Day 8. | Biological: Biostate® [RP]<br>* Single bolus intravenous dose of 50 IU/kg.<br>* Other names: Human Coagulation Factor VIII / von Willebrand Factor;|
| Experimental: Efficacy<br>Part 2: This arm includes all subjects during the efficacy component of the study. | Biological: Biostate® [SP]<br>* The dose is dependent on the reason for use and may consist of repeated bolus doses as required to manage haemophilia condition.<br>* Other names: Human Coagulation Factor VIII / von Willebrand Factor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemostatic efficacy |  | Monthly, until final study visit | 
| Number of treatments/units required to resolve any bleeding event |  | From Day 1 until final study visit | 
| FVIII concentrate usage (number of infusions, IU/kg per event, per month, and per year) |  | From Day 1 until final study visit | 
| Assessment of blood loss during any surgical procedure |  | From Day 1 until final study visit | 
| Pharmacokinetics of FVIII activity |  | Up to 48 hours following infusions (Part 1 and Part 3 only) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The nature, frequency and incidence of adverse events |  | From Day 1 until final study visit | 
| Development of FVIII inhibitors |  | From Day 1 until final study visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia A