Study of a pd VWF/FVIII Concentrate, Biostate®, in Subjects With Von Willebrand Disease

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to assess the pharmacokinetics (PK), efficacy, and safety of Biostate® in subjects with Von Willebrand Disease (VWD). Pharmacokinetic Component: PK parameters will be determined from a subgroup of subjects. Subjects who complete the PK component will subsequently continue in the efficacy component of the study, either continuing on a previously established prophylaxis regimen or continuing to receive on-demand treatment with the occurrence of non-surgical bleeding (NSB) events. Efficacy Component: Three treatment arms are defined for the efficacy component of the study. (1) Subjects who are currently being treated on a set prophylaxis regimen with a VWF product at the time of study entry will be enrolled in the Prophylaxis arm. (2) Subjects not being treated on a set prophylaxis regimen at the time of study entry who require a VWF product for the treatment of NSB events will be enrolled in the On-demand arm and commence using Biostate in the treatment of NSB events. (3) Subjects enrolled in the On-demand arm have the possibility to enter the Cross-over to Prophylaxis arm to receive an additional 12 months of prophylactic treatment.

Official Title
-----------------
An Open-label, Multi-centre Study to Assess the Pharmacokinetics, Efficacy and Safety of Biostate® in Subjects With Von Willebrand Disease.

Conditions
-----------------
Von Willebrand Disease

Intervention / Treatment
-----------------
* Biological: Biostate®
* Biological: Biostate®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed with VWD Desmopressin acetate (DDAVP) treatment is ineffective or contraindicated or not available Evidence of vaccination against hepatitis A and B (or presence of antibodies against hepatitis A and B) within 10 years prior to their first dose of Biostate® Written informed consent given Exclusion Criteria (for participation in the PK component): Actively bleeding immediately prior to initial PK period Have received DDAVP or a VWF product in the 5 days prior to their first dose of study product Have Type 2B, 2N or 2M VWD Exclusion Criteria (for all subjects): Requiring a VWF product for a planned surgical procedure at enrolment Have received aspirin or other non-steroidal anti-inflammatory drugs within 7 days prior to their first dose of study product Known history of, or are suspected to have, VWF or FVIII inhibitors Suffering an acute or chronic medical condition, other than VWD, which may affect the conduct of the study Known or suspected hypersensitivity or previous evidence of severe side effects to Biostate®, VWF/FVIII concentrates, or human albumin Impaired liver function at screening Evidence or a history (within the previous 12 months) of abuse of any drug substance, licit or illicit Participation in a clinical study or use of an investigational compound in the 3 months preceding the first day of study drug administration, or plans to enter such a study during the study period. Females who are pregnant, breast-feeding or who have a positive pregnancy test at screening

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PK<br>Includes subjects participating in the pharmacokinetic component of the study. | Biological: Biostate®<br>* 80 IU vWF/kg administered as a bolus intravenous infusion on Day 1 and approximately Day 180<br>* Other names: Human Coagulation Factor VIII / von Willebrand Factor;|
| Experimental: Prophylaxis<br>Includes subjects receiving 12 months of prophylactic therapy. | Biological: Biostate®<br>* Frequency and dose will be determined by the Investigator based on the subjects clinical condition, previous VWF concentrate requirements, response to therapy, weight and reason for usage.<br>* Other names: Human Coagulation Factor VIII / von Willebrand Factor;|
| Experimental: On-demand<br>Includes subjects receiving 12 months of on-demand treatment. | Biological: Biostate®<br>* Frequency and dose will be determined by the Investigator based on the subjects clinical condition, previous VWF concentrate requirements, response to therapy, weight and reason for usage.<br>* Other names: Human Coagulation Factor VIII / von Willebrand Factor;|
| Experimental: Cross-over to prophylaxis<br>Includes subjects completing 12 months of on-demand treatment (the On-demand arm) who cross-over to prophylactic therapy for an additional 12-month period. | Biological: Biostate®<br>* Frequency and dose will be determined by the Investigator based on the subjects clinical condition, previous VWF concentrate requirements, response to therapy, weight and reason for usage.<br>* Other names: Human Coagulation Factor VIII / von Willebrand Factor;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemostatic efficacy at time of non-surgical bleeding (NSB) event |  | From Day 1 until final study visit | 
| Haemostatic efficacy overall |  | Monthly (prophylactic therapy) or once every 3 months (for on-demand use) | 
| Number of treatments with blood product transfusions required to resolve any bleeding event |  | From Day 1 until final study visit | 
| vWF/FVIII concentrate usage (number of infusions, IU/kg per dose, 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 | 
| Number of spontaneous or traumatic NSB events |  | From Day 1 until final study visit | 
| Pharmacokinetic parameters for vWF and FVIII (PK arm only) |  | Up to 72 hours following infusions on Day 1 and approximately Day 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of FVIII inhibitors |  | From Day 1 until final study visit | 
| Development of vWF inhibitors |  | From Day 1 until final study visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Von Willebrand Disease