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Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT01541527
Other study ID # UF 8844
Secondary ID
Status Withdrawn
Phase N/A
First received February 17, 2012
Last updated December 30, 2014
Start date February 2012
Est. completion date August 2013

Study information

Verified date February 2012
Source University Hospital, Montpellier
Contact n/a
Is FDA regulated No
Health authority France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Study type Observational

Clinical Trial Summary

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.


Recruitment information / eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective


Related Conditions & MeSH terms


Intervention

Biological:
blood test
One blood test entering in the usual follow-up of the patient

Locations

Country Name City State
France CHU de Montpellier- Centre administratif André Benech Montpellier

Sponsors (7)

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

Country where clinical trial is conducted

France, 

References & Publications (3)

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

Outcome

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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