Study of Biostate for Treatment of Children With Hemophilia A Complicated by Antibody Development

Study Overview
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Brief Summary
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This is a clinical study to investigate how well Biostate works in treatment of male patients below the age of 12 years who have a clotting factor deficiency that is aggravated by the development of antibodies. The antibodies are directed against the clotting factor that is given for replacement therapy and usually make therapy unsuccessful. The treatment used in this study is called immune tolerance therapy.

Official Title
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A Multicentre, Interventional, Non-randomized, Open-label, Single-group Phase III Study to Evaluate Plasma-Derived Antihaemophilic Factor/Von Willebrand Factor Concentrate (Biostate®) for Immune Tolerance Induction in Male Paediatric Subjects With Haemophilia A (≤ 2%) Who Have Developed High-titre Antibodies to Factor VIII (Factor VIII Inhibitors)

Conditions
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Hemophilia A

Intervention / Treatment
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* Biological: Biostate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects diagnosed with haemophilia A (≤ 2% FVIII level in the absence of factor replacement, according to their medical history). Age 28 days to <12 years. Subject is eligible for immune tolerance induction (ITI) therapy Exclusion Criteria: The subject has received ITI previously. Subjects with a historical peak inhibitor titre of ≥ 200 BU/mL. Concomitant treatment with drugs with immunosuppressive side effects (eg, systemic corticosteroids), azathioprine, cyclophosphamide, high dose immunoglobulin or the use of a protein A column or plasmapheresis and interferons. High risk of cardiovascular, cerebrovascular, or other thromboembolic events (excluding catheter thrombosis) as judged by the investigator. Subjects who are human immunodeficiency virus (HIV)-1 or HIV-2 positive (as reported in the medical records or determined at screening).

Ages Eligible for Study
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Minimum Age: 28 Days
Maximum Age: 11 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biostate<br> | Biological: Biostate<br>* 200 IU/kg administered daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to immune tolerance induction (ITI) treatment | Number of subjects who achieve complete, partial, and no response (ITI failure) to treatment. | 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FVIII inhibitor titre |  | Up to 65 months | 
| Time to complete response (success) |  | Up to 65 months | 
| Time to inhibitor titer <0.6 BU/mL for the first time |  | Up to 65 months | 
| Thromboembolic complications | Number of patients with clinical symptoms or increased markers of coagulation activation | Up to 65 months | 
| Frequency of bleeding events |  | Up to 65 months | 
| Number of bleeding events per patient |  | Up to 65 months | 
| Severity of bleeding events per patient |  | Up to 65 months | 
| Catheter-related complications | Number of line infections | Up to 65 months |