Hemophilia A Clinical Trial
Official title:
Prevalence and Epitope Specificity of Non-neutralizing Antibodies in Haemophilia A Patients Without Inhibitors, Immunogenicity of B Domain: A Prospective Study
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.
Status | Withdrawn |
Enrollment | 0 |
Est. completion date | August 2013 |
Est. primary completion date | February 2013 |
Accepts healthy volunteers | No |
Gender | Male |
Age group | 6 Years and older |
Eligibility |
Inclusion Criteria: - male with Age > 6 years - Severe, moderate or mild treated HA patients with negative inhibitor titer (<0.6UB) - An information form will be presented to the patient or his/her legal representative by the physician who includes the patient in the study protocol - Patient with national insurance Exclusion Criteria: - Patient without his agreement for this study - Patient deprived of freedom - Patient without national insurance |
Observational Model: Cohort, Time Perspective: Prospective
Country | Name | City | State |
---|---|---|---|
France | CHU de Montpellier- Centre administratif André Benech | Montpellier |
Lead Sponsor | Collaborator |
---|---|
University Hospital, Montpellier | Centre Hospitalier Universitaire de Nice, Centre Hospitalier Universitaire de Nimes, Centre Hospitalier Universitaire de Saint Etienne, Hôpital de la Timone, University Hospital, Clermont-Ferrand, University Hospital, Toulouse |
France,
Lavigne-Lissalde G, Lacroix-Desmazes S, Wootla B, Tarrade C, Schved JF, Kaveri SV, Granier C, Villard-Saussine S. Molecular characterization of human B domain-specific anti-factor VIII monoclonal antibodies generated in transgenic mice. Thromb Haemost. 20 — View Citation
Lavigne-Lissalde G, Rothschild C, Pouplard C, Lapalud P, Gruel Y, Schved JF, Granier C. Characteristics, mechanisms of action, and epitope mapping of anti-factor VIII antibodies. Clin Rev Allergy Immunol. 2009 Oct;37(2):67-79. doi: 10.1007/s12016-009-8119 — View Citation
Lavigne-Lissalde G, Tarrade C, Lapalud P, Chtourou S, Schved JF, Granier C, Villard-Saussine S. Simultaneous detection and epitope mapping of anti-factor VIII antibodies. Thromb Haemost. 2008 Jun;99(6):1090-6. doi: 10.1160/TH07-08-0497. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | NNA prevalence | 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. |
18 months | No |
Secondary | Relationship between clinical and biological parameters and NNA presence | 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. |
18 months | No |
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