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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Hemophilia A
• Intervention / Treatment: Biological: Biostate

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • Study Site
• Germany
  • Frankfurt, Germany
    • Study Site
  • Hamburg, Germany
    • Study Site
• Greece
  • Athens, Greece
    • Study Site
  • Thessaloniki, Greece
    • Study Site
• Italy
  • Milano, Italy
    • Study Site
• Russian Federation
  • Barnaul, Russian Federation
    • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biostate	Biological: Biostate; 200 IU/kg administered daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Principal Investigator: Carmen Escuriola-Ettingshausen, Haemophilia Centre Rhein Main, Frankfurt - Mörfelden

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: September 30, 2011
• First Submitted That Met QC Criteria: September 30, 2011
• First Posted (Estimate): October 3, 2011

Study Record Updates

• Last Update Posted (Actual): October 3, 2017
• Last Update Submitted That Met QC Criteria: October 2, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: CSLCT-BIO-10-67; 2010-020113-85 (EudraCT Number)