Ignite Creation Date:
2025-12-25 @ 5:08 AM
Ignite Modification Date:
2025-12-26 @ 4:12 AM
Study NCT ID:
NCT01541527
Status:
WITHDRAWN
Last Update Posted:
2014-12-31
First Post:
2012-02-17
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Non Neutralizing Antibodies: Prevalence and Characterization
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006467', 'term': 'Hemophilia A'}], 'ancestors': [{'id': 'D025861', 'term': 'Blood Coagulation Disorders, Inherited'}, {'id': 'D001778', 'term': 'Blood Coagulation Disorders'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D020147', 'term': 'Coagulation Protein Disorders'}, {'id': 'D006474', 'term': 'Hemorrhagic Disorders'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D006403', 'term': 'Hematologic Tests'}], 'ancestors': [{'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': "Promoter's change", 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2012-02'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2012-02', 'completionDateStruct': {'date': '2013-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2014-12-30', 'studyFirstSubmitDate': '2012-02-17', 'studyFirstSubmitQcDate': '2012-02-23', 'lastUpdatePostDateStruct': {'date': '2014-12-31', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2012-03-01', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2013-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'NNA prevalence', 'timeFrame': '18 months', 'description': '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.\n\nThe investigators will evaluate the NNA prevalence by the x-MAP technology.'}], 'secondaryOutcomes': [{'measure': 'Relationship between clinical and biological parameters and NNA presence', 'timeFrame': '18 months', 'description': '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.\n\nThe investigators will evaluate the secondary outcomes by the x-MAP technology.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['non neutralizing antibody', 'Epitopic profile', 'Clinical relevance'], 'conditions': ['Hemophilia A']}, 'referencesModule': {'references': [{'pmid': '19172415', 'type': 'RESULT', '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/s12016-009-8119-0.'}, {'pmid': '18521513', 'type': 'RESULT', '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.'}, {'pmid': '17598006', 'type': 'RESULT', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nIn 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).\n\nAmong 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%.\n\nConsidering 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.\n\nHowever, in 2006, Dimichele advancedf a hypothesis concerning the influence of NNA on the variations in the kinectics of FVIII observed in certain patients.\n\nThe mechanism explaining the role of these NNA in the FVIII in the FVIII kinectics has not still been demonstrated.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '6 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'severe, moderate and mild HA patients (sex: Male and age \\> 6 years)', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* male with Age \\> 6 years\n* Severe, moderate or mild treated HA patients with negative inhibitor titer (\\<0.6UB)\n* 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\n* Patient with national insurance\n\nExclusion Criteria:\n\n* Patient without his agreement for this study\n* Patient deprived of freedom\n* Patient without national insurance'}, 'identificationModule': {'nctId': 'NCT01541527', 'briefTitle': 'Non Neutralizing Antibodies: Prevalence and Characterization', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Montpellier'}, 'officialTitle': 'Prevalence and Epitope Specificity of Non-neutralizing Antibodies in Haemophilia A Patients Without Inhibitors, Immunogenicity of B Domain: A Prospective Study', 'orgStudyIdInfo': {'id': 'UF 8844'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'severe, moderate and mild HA patients', 'description': 'one Arm: biological collection of 300 severe, moderate and mild HA patients', 'interventionNames': ['Biological: blood test']}], 'interventions': [{'name': 'blood test', 'type': 'BIOLOGICAL', 'description': 'One blood test entering in the usual follow-up of the patient', 'armGroupLabels': ['severe, moderate and mild HA patients']}]}, 'contactsLocationsModule': {'locations': [{'zip': '3400', 'city': 'Montpellier', 'country': 'France', 'facility': 'CHU de Montpellier- Centre administratif André Benech', 'geoPoint': {'lat': 43.61093, 'lon': 3.87635}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Montpellier', 'class': 'OTHER'}, 'collaborators': [{'name': 'Hôpital de la Timone', 'class': 'OTHER'}, {'name': 'University Hospital, Clermont-Ferrand', 'class': 'OTHER'}, {'name': 'Centre Hospitalier Universitaire de Saint Etienne', 'class': 'OTHER'}, {'name': 'University Hospital, Toulouse', 'class': 'OTHER'}, {'name': 'Centre Hospitalier Universitaire de Nice', 'class': 'OTHER'}, {'name': 'Centre Hospitalier Universitaire de Nīmes', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}