Rheumatoid ArthritisABI-RANCT02116504
Anti-Biopharmaceutical Immunization: Prediction and Analysis of Clinical Relevance to Minimize the Risk of Immunization in Rheumatoid Arthritis Patients or Juvenile Idiopathic Arthritis Patients
A study testing Sampling of blood in people with Rheumatoid Arthritis and Juvenile Idiopathic Arthritis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Rheumatoid Arthritis, Juvenile Idiopathic Arthritis
- What is being tested?
- Sampling of blood
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2014to Nov 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the detailed 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.
- Being tested
- Sampling of blood
- Keywords
- Rheumatoid arthritis, Juvenile Idiopathic Arthritis, Biopharmaceutical, Immunogenicity, Anti-Drug Antibody, Prediction
- Medical subject headings
- Arthritis, Rheumatoid, Arthritis, Juvenile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sampling of bloodProcedure or surgery
Sampling of blood for dosage of antibodies
| Study group | Role | What they receive |
|---|---|---|
| Global population | Other | All included patients :
Sampling of blood Receives: Procedure: Sampling of blood |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immunization against the Biopharmaceutical defined by the presence of ADAb within the first 12 months (or W52)
Measured: 52 weeks
Secondary outcomes (15)
Quantification of ADAb
Measured: at Week 0
Quantification of ADAb
Measured: at Week 4
Quantification of ADAb
Measured: at Week 12
Quantification of ADAb
Measured: at Week 26
Quantification of ADAb
Measured: at Week 52
Quantification of ADAb
Measured: at Week 64
Quantification of ADAb
Measured: at Week 78
Clinical response and remission
European League Against Rheumatism (EULAR) response
Measured: at Week 4
Clinical response and remission
European League Against Rheumatism (EULAR) response
Measured: at Week 12
Clinical response and remission
European League Against Rheumatism (EULAR) response
Measured: at Week 26
Clinical response and remission
European League Against Rheumatism (EULAR) response
Measured: at Week 52
Clinical response and remission
European League Against Rheumatism (EULAR) response
Measured: at Week 64
Clinical response and remission
European League Against Rheumatism (EULAR) response
Measured: at Week 78
ADAb-associated adverse clinical events at any time point
Measured: Until Week 78
Drug levels
Concentration in mg/L
Measured: Until week 78
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2014 (estimated)
- Study startApr 2014
- Primary completionApr 2016
- Study completionNov 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 156 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Leiden University Medical Center, University College London (UCL) Cancer Institute, University of Florence, Pediatric Rheumatology International Trials Organization, Istituto Giannina Gaslini, GlaxoSmithKline, University Hospital, Tours
- Responsible party
- Sponsor
- Investigators
- Xavier Mariette, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02116504
- Sponsor's protocol ID
- ABI-RA-P01
- Other IDs
- 2013-A01268-37
- Acronym
- ABI-RA
- Status last verified
- Aug 2016
- First submitted
- 3 Apr 2014
- Last updated
- 28 Nov 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 35281074Duhaze 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.
PubMed 32192445Bitoun 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.
PubMed 29936438
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02116504
- Acronym / sponsor ID
- ABI-RA / ABI-RA-P01
- Keywords
- Rheumatoid arthritis, Juvenile Idiopathic Arthritis, Biopharmaceutical, Immunogenicity, Anti-Drug Antibody, Prediction
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 156 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Leiden University Medical Center, University College London (UCL) Cancer Institute, University of Florence, Pediatric Rheumatology International Trials Organization, Istituto Giannina Gaslini, GlaxoSmithKline, University Hospital, Tours
- Study start
- Apr 2014
- Primary completion
- Apr 2016 (actual)
- Study completion
- Nov 2017 (estimated)
- First posted
- 17 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Global population | Other | Procedure: Sampling of bloodAll included patients : Sampling of blood |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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:
- Pregnant or breast-feeding women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sampling of bloodSampling of blood for dosage of antibodies | Procedure or surgery | Global population |
Primary outcome
Immunization against the Biopharmaceutical defined by the presence of ADAb within the first 12 months (or W52)
Time frame: 52 weeks
15 secondary outcomes
Quantification of ADAb
Time frame: at Week 0
Quantification of ADAb
Time frame: at Week 4
Quantification of ADAb
Time frame: at Week 12
Quantification of ADAb
Time frame: at Week 26
Quantification of ADAb
Time frame: at Week 52
Quantification of ADAb
Time frame: at Week 64
Quantification of ADAb
Time frame: at Week 78
Clinical response and remission
Time frame: at Week 4
Clinical response and remission
Time frame: at Week 12
Clinical response and remission
Time frame: at Week 26
Clinical response and remission
Time frame: at Week 52
Clinical response and remission
Time frame: at Week 64
Clinical response and remission
Time frame: at Week 78
ADAb-associated adverse clinical events at any time point
Time frame: Until Week 78
Drug levels
Time frame: Until week 78
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2016.
- Derived from this study: PubMed 35281074Paoletti 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.
- Derived from this study: PubMed 32192445Duhaze 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.
- Derived from this study: PubMed 29936438Bitoun 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xavier Mariette, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sampling of blood in people with Rheumatoid Arthritis and Juvenile Idiopathic Arthritis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immunization against the Biopharmaceutical defined by the presence of ADAb within the first 12 months (or W52) (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02116504, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2016.