Non Neutralizing Antibodies: Prevalence and Characterization

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by University Hospital, Montpellier.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Hôpital de la Timone
University Hospital, Clermont-Ferrand
Centre Hospitalier Universitaire de Saint Etienne
University Hospital, Toulouse
Centre Hospitalier Universitaire de Nice
Centre Hospitalier Universitaire de Nīmes
Information provided by (Responsible Party):
University Hospital, Montpellier
ClinicalTrials.gov Identifier:
NCT01541527
First received: February 17, 2012
Last updated: February 23, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention
Hemophilia A
Biological: blood test

Study Type: Observational
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

Resource links provided by NLM:


Further study details as provided by University Hospital, Montpellier:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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.



Estimated Enrollment: 300
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)
Groups/Cohorts Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

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

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01541527

Contacts
Contact: Schved Jean-François, PU-PH 33 (0)4 67 33 70 31 schvedjf@aol.com

Locations
France
CHU de Montpellier- Centre administratif André Benech Recruiting
Montpellier, France, 3400
Contact: Schved Jean-François, PU-PH    33(0)4 67 33 70 31    schvedjf@aol.com   
Contact: Bonnafoux Benoit, clinical research engineer    33 (0)4 67 33 90 98    b-bonnafoux@chu-montpellier.fr   
Principal Investigator: Schved Jean-Francois, PU-PH         
Sponsors and Collaborators
University Hospital, Montpellier
Hôpital de la Timone
University Hospital, Clermont-Ferrand
Centre Hospitalier Universitaire de Saint Etienne
University Hospital, Toulouse
Centre Hospitalier Universitaire de Nice
Centre Hospitalier Universitaire de Nīmes
  More Information

Publications:
Responsible Party: University Hospital, Montpellier
ClinicalTrials.gov Identifier: NCT01541527     History of Changes
Other Study ID Numbers: UF 8844
Study First Received: February 17, 2012
Last Updated: February 23, 2012
Health Authority: Afssaps: French Health Products Safety Agency

Keywords provided by University Hospital, Montpellier:
non neutralizing antibody
Epitopic profile
Clinical relevance

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Antibodies
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014