Non Neutralizing Antibodies: Prevalence and Characterization

NCT01541527 | Withdrawn

• 1 other identifier: UF 8844
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hemophilia A

Keywords

non neutralizing antibody; Epitopic profile; Clinical relevance

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Relationship between clinical and biological parameters and NNA presence

  18 months

Study Arms (1)

severe, moderate and mild HA patients

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

Biological: blood test

Interventions

blood test BIOLOGICAL

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

severe, moderate and mild HA patients

Eligibility Criteria

• Age: 6 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

severe, moderate and mild HA patients (sex: Male and age \> 6 years)

You may qualify if:

• 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

You may not qualify if:

• Patient without his agreement for this study
• Patient deprived of freedom
• Patient without national insurance

Sponsors & Collaborators

• University Hospital, Montpellier: lead
• Hôpital de la Timone: collaborator
• University Hospital, Clermont-Ferrand: collaborator
• Centre Hospitalier Universitaire de Saint Etienne: collaborator
• University Hospital, Toulouse: collaborator
• Centre Hospitalier Universitaire de Nice: collaborator
• Centre Hospitalier Universitaire de Nīmes: collaborator

Study Sites (1)

CHU de Montpellier- Centre administratif André Benech

Montpellier, 3400, France

Location

Related Publications (3)

• 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.

  PMID: 19172415 RESULT

• 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.

  PMID: 18521513 RESULT

• 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.

  PMID: 17598006 RESULT

MeSH Terms

Conditions

Hemophilia A

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2012
• First Posted: March 1, 2012
• Study Start: February 1, 2012
• Primary Completion: February 1, 2013
• Study Completion: August 1, 2013
• Last Updated: December 31, 2014

Record last verified: 2012-02

Locations

FR (1)