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

Rheumatoid Arthritis Clinical Trial

— ABI-RA  

Official title:

Multi-center Prospective European Cohort Study in Patients With Rheumatoid Arthritis or Juvenile Idiopathic Arthritis Planned to be Treated Independently of the Present Study, With the First Line of Adalimumab, Etanercept, Infliximab Therapy or With Rituximab or Tocilizumab (After Anti-Tumor Necrosis Factor Therapy or Another Biotherapy or in First Line)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02116504
• Other study ID #: ABI-RA-P01
• Secondary ID: 2013-A01268-37
• Status: Active, not recruiting
• Phase: N/A
• First received: April 3, 2014
• Last updated: November 24, 2016
• Start date: April 2014
• Est. completion date: November 2017

Study information

• Verified date: August 2016
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Description:

The ABIRISK (Anti-biopharmaceutical Immunization: Prediction and analysis of clinical relevance to minimize the risk) consortium, within the IMI (Innovative Medicines Initiative), is a Public Private Partnership between pharmaceutical companies, academic institutions and clinical centers. The ABIRISK aims are to better analyze and predict the phenomenon of immunogenicity in order to reduce its occurrence. One of the main objectives of ABIRISK is to set up prospective cohort (ABI-RA) of patients with rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA) to provide, using an integrated approach, new tools for being able to detect earlier and even before the beginning of the therapy, immunization to biopharmaceutical (BP). The introduction of BP has been a critical step forward in care for RA/JIA and 9 BP are now licensed for the treatment of RA/JIA. In spite of this progress, failure of response to BP is frequent and in most of the registries, less than 50 % of patients are still on drug at 5 years. These failures may be primary failures or secondary failures. The fact is that the low level of responses becomes insufficient compared to the expectations. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 156
• Est. completion date: November 2017
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years and older

Eligibility

Inclusion Criteria:

• 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:

• etanercept, adalimumab, infliximab, infliximab Biosimilar, rituximab OR tocilizumab in first line or after failure with other biotherapy. In case of previous rituximab, inclusion may be possible at least 6 months after the last rituximab infusion therapy or,

• 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

Exclusion Criteria:

• 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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Health Services Research

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Arthritis, Rheumatoid
• Juvenile Idiopathic Arthritis
• Rheumatoid Arthritis

Intervention

Procedure:
• Sampling of blood
Sampling of blood for dosage of antibodies

Locations

Country	Name	City	State
France	CHU Bicêtre	Le Kremlin-Bicêtre

Sponsors (10)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), GlaxoSmithKline, Institut National de la Santé Et de la Recherche Médicale, France, Istituto Giannina Gaslini, Leiden University Medical Center, Pediatric Rheumatology International Trials Organization, Università di Firenze (UNIFI) Italy, University College London (UCL) Cancer Institute, University Hospital, Tours

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunization against the Biopharmaceutical defined by the presence of ADAb within the first 12 months (or W52)		52 weeks	No
Secondary	Quantification of ADAb		at Week 0	No
Secondary	Quantification of ADAb		at Week 4	No
Secondary	Quantification of ADAb		at Week 12	No
Secondary	Quantification of ADAb		at Week 26	No
Secondary	Quantification of ADAb		at Week 52	No
Secondary	Quantification of ADAb		at Week 64	No
Secondary	Quantification of ADAb		at Week 78	No
Secondary	Clinical response and remission	European League Against Rheumatism (EULAR) response	at Week 4	No
Secondary	Clinical response and remission	European League Against Rheumatism (EULAR) response	at Week 12	No
Secondary	Clinical response and remission	European League Against Rheumatism (EULAR) response	at Week 26	No
Secondary	Clinical response and remission	European League Against Rheumatism (EULAR) response	at Week 52	No
Secondary	Clinical response and remission	European League Against Rheumatism (EULAR) response	at Week 64	No
Secondary	Clinical response and remission	European League Against Rheumatism (EULAR) response	at Week 78	No
Secondary	ADAb-associated adverse clinical events at any time point		Until Week 78	Yes
Secondary	Drug levels	Concentration in mg/L	Until week 78	No