Non Neutralizing Antibodies: Prevalence and Characterization

NCT ID: NCT01541527

Last Updated: 2014-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

WITHDRAWN

Study Classification

OBSERVATIONAL

Study Start Date

2012-02-29

Study Completion Date

2013-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hemophilia A

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

non neutralizing antibody Epitopic profile Clinical relevance

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

severe, moderate and mild HA patients

one Arm: biological collection of 300 severe, moderate and mild HA patients

blood test

Intervention Type BIOLOGICAL

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

blood test

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

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

6 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Hôpital de la Timone

OTHER

Sponsor Role collaborator

University Hospital, Clermont-Ferrand

OTHER

Sponsor Role collaborator

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role collaborator

University Hospital, Toulouse

OTHER

Sponsor Role collaborator

Centre Hospitalier Universitaire de Nice

OTHER

Sponsor Role collaborator

Centre Hospitalier Universitaire de Nīmes

OTHER

Sponsor Role collaborator

University Hospital, Montpellier

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

CHU de Montpellier- Centre administratif André Benech

Montpellier, , France

Site Status

Countries

Review the countries where the study has at least one active or historical site.

France

References

Explore related publications, articles, or registry entries linked to this study.

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/s12016-009-8119-0.

Reference Type RESULT
PMID: 19172415 (View on PubMed)

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.

Reference Type RESULT
PMID: 18521513 (View on PubMed)

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. 2007 Jul;98(1):138-47.

Reference Type RESULT
PMID: 17598006 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

UF 8844

Identifier Type: -

Identifier Source: org_study_id