Inhibitor study in patients with hemophilia never treated in the past

Conditions: Infants or children with severe hemophilia A previously untreated with factor concentrates.
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2013-002686-19-SE

Lead Sponsor: und University, Clinical Coagulation Research Unit, Skane University Hospital

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Male

Target Recruitment: 50

Inclusion Criteria

1) An informed consent, approved by the appropriate institutional Review Board (IRB)/Independent Ethics Committee (IEC) has been administered, signed and dated by the parents or legal representative of the parents
2) Subject diagnosed with severe hemophilia A defined by baseline FVIII:C <0.01 IU/mL. FVIII activity has to be confirmed by a central lab. If the confirmatory level is not <0.01IU/mL the child must exit the study.
3) Subject weighs 3.5 kg or more at the time of his baseline study evaluation
Are the trial subjects under 18? yes
Number of subjects for this age range: 50
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Subjects with prior exposure to clotting factor concentration or blood products.
2) Subjects with a clinically significant chronic disease other than hemophilia A
3) Subjects that are currently participating in another investigational clinical trial

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to evaluate the changes in the immune system upon exposure to FVIII with severe hemophilia A;Secondary Objective: The secondary objective is to identify predictors of FVIII inhibitor development or tolerance to FVIII infusions;Primary end point(s): In relation to the primary endpoints, an inhibitor is defined by a Nijmegen test >0.6 BU in two consecutive tests conducted in the central lab. During the first 50 days of exposure to a single FVIII product, the following items will be evaluated:<br>- FVIII inhibitor<br>- FVIII antibody titer, subclasses and FVIII-binding affinity<br>- FVIII-specific T-cell responses<br>- Total number of FOXP-3-positive T reg<br>- RNA expression for the whole transcriptome<br>- F8 gene mutation and other known genomic predictors for inhibitor development;Timepoint(s) of evaluation of this end point: The inhibitor to FVIII will be evaluated during the following visits: day 1, 5, 10, 20, 30, 40 and 50.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secondary endpoints will be evaluated during the first 50 exposure days. The items recorded in this period are: FVIII usage, bleeding episodes, occurrence of infection and/or immunization;Timepoint(s) of evaluation of this end point: At study completion (after 50 exposure days or three years, what ever comes first)