This is a clinical study to investigate how well Biostate works in treatmentof male patients below the age of 12 years who have a clotting factordeficiency that is aggravated by the development of antibodies. Theantibodies are directed against the clotting factor that is given forreplacement therapy and usually make therapy unsuccessful. Thetreatment used in this study is called immune tolerance therapy

• Conditions: Male paediatric subjects with Haemophilia A who develped high titreantibodies to human coagulation Factor VIII; MedDRA version: 14.1Level: LLTClassification code 10018941Term: Haemophilia NOSSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2010-020113-85-DE
• Lead Sponsor: CSL Behring GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05-30
• Last Update Posted: 24 March 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 15

Inclusion Criteria

1. Male subjects diagnosed with haemophilia A (::;2% FVIII level in the
absence of factor replacement, according to their medical history).
2. Age 28 days to <12 years.
3. ITI treatment can be initiated if:
a. An inhibitor level of >5 and <200 BU/mL was confirmed in 2 repeated
tests by the central laboratory during the screening period and no
waiting period is required as judged by the investigator.
b. An inhibitor level of >5 and <200 BU/mL was confirmed in 2 repeated
tests by the central laboratory during the screening period and the
inhibitor titre decreased from the peak titre during a waiting period
(maximum 11 months) added at the discretion of the investigator.
c. A subject has pre-existing inhibitors, determined no more than 11
months prior to the Screening visit, which decreased from the peak titre,
and an inhibitor level of >5 and <200 BU/mL was confirmed in 2
repeated tests by the central laboratory during the screening period. A
waiting period could still be added if the total duration from inhibitor
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diagnosis until start of IT! treatment (ie, including the screening period)
does not exceed 12 months.
4. The subject and/or his legally acceptable representative understand
the nature of the study and have given written informed consent to
participate in the study.
5. Sufficient peripheral venous access or central venous line.
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion Criteria:
l.DThe subject has received IT! previously.
2.DSubjects with a historical peak inhibitor titre of ~200 BU/mL.
3.DConcomitant treatment with drugs with immunosuppressive side
effects (eg, systemic cortlcosteroids), azathioprine, cyclophosphamide,
high dose immunoglobulin or the use of a protein A column or
plasmapheresis and interferons.
4.DHigh risk of cardiovascular, cerebrovascular, or other
thromboembolic events (excluding catheter thrombosis) as judged by
the investigator.
5. DSubjects who are human immunodeficiency virus (HIV)-l or HIV-2
positive (as reported in the medical records or determined at screening).
6.DThe subject has evidence or a history (within the previous 12
months) of abuse of any drug substance, licit or illicit.
7.DThe subject has a known or suspected hypersensitivity or has
previous evidence of severe side effects to von Willebrand factor
(VWF)/FVIII or FVIII concentrates or human albumin.
S.DThe subject has participated in a clinical study or used an
investigational compound (eg, a new chemical entity not approved for
clinical use) in the past 3 months, unless the study was for haemophilia
A and the subject developed an inhibitor (then, a wash-out period of at
least 4 weeks must be applied), or is planning to enter such a study
during the study period.
9.DSubjects or legal guardians/ representatives with suspected inability
(eg, language problems) or unwillingness to comply with study
procedures.
10.DThe subject has an acute or chronic medical condition other than
haemophilia A, which may, in the opinion of the investigator, affect the
conduct of the study.
l1.DMental condition rendering the subject (or the subject's legally
acceptable representative) unable to understand the nature, scope and
possible consequences of the study).
12.DAny condition that is likely to interfere with evaluation of the
investigational medicinal product (IMP) or satisfactory conduct of the
study.
13.DEmployee at the study site, or spouse/partner or relative of the
investigator or subinvestigators.
Study Product, Dose, and Mode of Administration:
The IMP Biostate will be intravenously (I.v.) administered at a daily dose
of 200 international units (IU)/kg body weight (b.w.), preferably split
into 2 doses of 100 IU/kg b.w. per day.
For subjects with an undetectable inhibitor titre «0.6 BU/mL) at 2
consecutive assessments, tested at intervals of 2 weeks (±3 days), and
normal recovery (~66% of predicted) for 6-S weeks, the daily Biostate
dose will be reduced by 20 IU/kg b.w. (ie, by 10% of the initial daily ITI
dose), if possible, every 2-4 weeks down to a dose of 100 IU/kg b.w.,
provided the recovery remains normal during that time (assessed
weekly).
After further gradual reduction of the dose and extension of the administration interval (at the discretion of the investigator), Biostate
will be administered as prophylaxis at a daily dose of 50 IU/kg b.w, on 3
days per week (about every second day).
Any daily dose'~100IU/kg b.w. should preferably be evenly split into 2
doses per day. Daily doses of 100 IU/kg b.w. or lower will be
administered once daily.
Bleeding complications during the tolerization period should be treated
according to centre's standard of care. Study treatment should not be
interrupted for surgical procedures.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified