Anti-Biopharmaceutical Immunization: Prediction and Analysis of Clinical Relevance to Minimize the Risk of Immunization in Rheumatoid Arthritis Patients or Juvenile Idiopathic Arthritis Patients

NCT02116504 | Unknown

• 2 other identifiers: ABI-RA-P012013-A01268-37
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

Brief Summary

One of the main potential causes of these failures of BP therapy response is the development of Anti-drug Anti-body (ADAb) in some patients. ADAb may decrease the efficacy of BPs by neutralizing them or modifying their clearance and they may be associated with BP-specific hypersensitivity reactions. The prediction, prevention and cure of anti-drug (AD) immunization are thus major goals in BP development. This prospective study (ABI-RA) will assess the occurrence of ADAb using standardized and validated assay(s) and also cellular, genetic and molecular parameters in RA/JIA patients treated with adalimumab, etanercept, infliximab and rituximab or tocilizumab, to address the mechanism of immunogenicity. Patient-related factors that might predispose an individual to an immune response will be taken into account: underlying disease, genetic background, immune status, including immunomodulating therapy and dosing schedule.

Conditions

Rheumatoid Arthritis; Juvenile Idiopathic Arthritis

Keywords

Rheumatoid arthritis; Juvenile Idiopathic Arthritis; Biopharmaceutical; Immunogenicity; Anti-Drug Antibody; Prediction

Outcome Measures

Primary Outcomes (1)

• Immunization against the Biopharmaceutical defined by the presence of ADAb within the first 12 months (or W52)

  52 weeks

Secondary Outcomes (15)

• Quantification of ADAb

  at Week 0

• Quantification of ADAb

  at Week 4

• Quantification of ADAb

  at Week 12

• Quantification of ADAb

  at Week 26

• Quantification of ADAb

  at Week 52

Study Arms (1)

Global population

OTHER

All included patients : Sampling of blood

Procedure: Sampling of blood

Interventions

Sampling of blood PROCEDURE

Sampling of blood for dosage of antibodies

Global population

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients of more than 18 years old diagnosed with RA according to 2010 ACR/EULAR criteria Or Male and female patients Age \> 2 years and \<18 years, diagnosed with JIA according to the Internal League Against Rheumatism (ILAR) classification criteria.
• Patient for whom the Treating Physician has decided to prescribe in the usual manner in accordance with the terms of the marketing authorization and independently from entry into this study:
• Subcutaneous form of Tocilizumab, either as first line or after switch from infusion tocilizumab form is allowed.
• Having given written informed consent prior to undertaking any study-related procedures. For JIA patients, written informed consent signed by parents or legal representative and assent of the minor child
• Covered by a health insurance system where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research

You may not qualify if:

• Under any administrative or legal supervision.
• Patients having previously anti-TNF if they are going to receive another anti-TNF therapy
• Patients having previously received rituximab in the past 6 months.
• Conditions/situations such as:
• Patients with conditions/concomitant diseases making them non evaluable for the primary endpoint
• Impossibility to meet specific protocol requirements (e.g. blood sampling)
• Patient is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol
• Uncooperative or any condition that could make the patient potentially non-compliant to the study procedures
• Pregnant or breast-feeding women

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Leiden University Medical Center: collaborator
• University College London (UCL) Cancer Institute: collaborator
• University of Florence: collaborator
• Pediatric Rheumatology International Trials Organization: collaborator
• Istituto Giannina Gaslini: collaborator
• GlaxoSmithKline: collaborator
• University Hospital, Tours: collaborator

Study Sites (1)

CHU Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

Related Publications (3)

• Paoletti A, Ly B, Bitoun S, Nocturne G, Riviere E, Manson JJ, Matucci A, Pallardy M, De Vries N, Mariette X. Restoration of Default Blood Monocyte-Derived Macrophage Polarization With Adalimumab But Not Etanercept in Rheumatoid Arthritis. Front Immunol. 2022 Feb 23;13:832117. doi: 10.3389/fimmu.2022.832117. eCollection 2022.

  PMID: 35281074 DERIVED

• Duhaze J, Caubet M, Hassler S, Bachelet D, Allez M, Deisenhammer F, Fogdell-Hahn A, Gleizes A, Hacein-Bey-Abina S, Mariette X, Pallardy M, Broet P; ABIRISK Consortium. Assessing the effect of genetic markers on drug immunogenicity from a mechanistic model-based approach. BMC Med Res Methodol. 2020 Mar 20;20(1):69. doi: 10.1186/s12874-020-00941-z.

  PMID: 32192445 DERIVED

• Bitoun S, Nocturne G, Ly B, Krzysiek R, Roques P, Pruvost A, Paoletti A, Pascaud J, Donnes P, Florence K, Gleizes A, Hincelin-Mery A, Allez M, Hacein-Bey-Abina S, Mackay F, Pallardy M, Le Grand R, Mariette X. Methotrexate and BAFF interaction prevents immunization against TNF inhibitors. Ann Rheum Dis. 2018 Oct;77(10):1463-1470. doi: 10.1136/annrheumdis-2018-213403. Epub 2018 Jun 23.

  PMID: 29936438 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis, Juvenile

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Xavier Mariette, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2014
• First Posted: April 17, 2014
• Study Start: April 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: November 1, 2017
• Last Updated: November 28, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)