Non Neutralizing Antibodies: Prevalence and Characterization
Recruitment status was Recruiting
Antibodies (Abs) directed against factorVIII (FVIII) remain the main iatrogenic complication in haemophilia A (HA) patients. Anti-FVIII Abs inhibiting pro-coagulant properties of the molecule are named inhibitors whereas Abs directed towards non-functional epitopes are named non-neutralizing antibodies (NNA). These NNA are poorly studied and their prevalence is ill-defined.
In a recent retrospective study the investigators evaluated, in a cohort of 210 patients without inhibitor, the NNA prevalence and the NNA epitope specificity against the heavy chain (HC)or the light chain(LC). For the first time, the investigators used two x-MAP based assays: the first to determine the specificity of anti-FVIII Abs against the HC or the LC, the second to display Abs directed towards the B domain. NNA were found in 38 out of 210 patients (18).
Among this NNA positive population, 74% and 13% of patients had anti-FVIII Abs against both chains. The proportion of NNA directed towards the B domain was 18%.
Considering an approximate inhibitor prevalence of 30% and a NNA prevalence of 19% in severe HA patients, approximately 50% of severe HA patients develop an immune response against infused FVIII. Due to their unclear relevance, the NNA detection does not yet belong to the routine clinical practice.
However, in 2006, Dimichele advancedf a hypothesis concerning the influence of NNA on the variations in the kinectics of FVIII observed in certain patients.
The mechanism explaining the role of these NNA in the FVIII in the FVIII kinectics has not still been demonstrated.
The investigators propose to perform a multicentre prospective study with the aim to confirm, in severe, moderate and mild HA treated patietns, the NNA prevalence observed in our retrospective study, to study the evolution over time of the epitopemapping of these NNA and to explore the correlation between these NNA and clinical/biological parameters.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Prevalence and Epitope Specificity of Non-neutralizing Antibodies in Haemophilia A Patients Without Inhibitors, Immunogenicity of B Domain: A Prospective Study|
- NNA prevalence [ Time Frame: 18 months ] [ Designated as safety issue: No ]
The primary outcome is the study of the development of ANN anti-FVIII at the severe, moderate or mild HA patients to establish prevalency of ACs targeted against the heavy chain, the light chain and the domains of the FVIII (6 months after the inclusion.
The investigators will evaluate the NNA prevalence by the x-MAP technology.
- Relationship between clinical and biological parameters and NNA presence [ Time Frame: 18 months ] [ Designated as safety issue: No ]
The secondary outcomes assess the evolution in time of these Acs of isotypes IgG and the relationship between clinical and biological parameters (FVIII%, recovery,..) and NNA presence.
The investigators will evaluate the secondary outcomes by the x-MAP technology.
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||August 2013|
|Estimated Primary Completion Date:||February 2013 (Final data collection date for primary outcome measure)|
severe, moderate and mild HA patients
one Arm: biological collection of 300 severe, moderate and mild HA patients
Biological: blood test
One blood test entering in the usual follow-up of the patient
Please refer to this study by its ClinicalTrials.gov identifier: NCT01541527
|Contact: Schved Jean-François, PU-PH||33 (0)4 67 33 70 firstname.lastname@example.org|
|CHU de Montpellier- Centre administratif André Benech||Recruiting|
|Montpellier, France, 3400|
|Contact: Schved Jean-François, PU-PH 33(0)4 67 33 70 31 email@example.com|
|Contact: Bonnafoux Benoit, clinical research engineer 33 (0)4 67 33 90 98 firstname.lastname@example.org|
|Principal Investigator: Schved Jean-Francois, PU-PH|