- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02840175
Treatment Tapering in JIA With Inactive Disease (AJIBIOREM)
March 31, 2021 updated by: Assistance Publique - Hôpitaux de Paris
Treatment Tapering in Oligoarticular or Rheumatoid Factor Negative Polyarticular Juvenile Idiopathic Arthritis With Inactive Disease on Biologic Therapy
As biologic treatments are expensive and associated with some concerns regarding long-term safety, investigator hypothesize that early tapering and then withdrawal of biological agent, in an homogenous group of children with juvenile idiopathic arthritis achieving inactive disease, is safe and not inferior to the maintenance of stable treatment intensity over 24 weeks.
In addition, investigator also hypothesize that an earlier tapering of treatment is associated with a better quality-of-life and a general cost saving effect.
MRP8/14 will be studied as a potential biomarker for the risk of relapse.
A study for biologic agent, anti-biologic agent antibodies and a pharmacogenomic approach will complete the research, as pharmacokinetic study during withdrawal of biologic treatment are rare in children.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Juvenile idiopathic arthritis (JIA) is characterized by chronic arthritis of unknown etiology starting before the age of 16.
There are four to five thousand paediatric patients with JIA in France.
Most of these patients are diagnosed with oligoarticular or rheumatoid factor negative polyarticular JIA.
The prognosis of the disease has dramatically improved thanks to the introduction of biologic agents in patients with an extended oligoarticular or rheumatoid factor negative polyarticular JIA and inadequate response to methotrexate.
Inactive disease and long-lasting clinical remission are achieved in most cases.
"Treat to target" approaches are increasingly recommended, with earlier introduction of biologics, however the way to taper or withdraw treatment in patients achieving inactive disease is not codified.
As biologic treatments are expensive and associated with some concerns regarding long-term safety, this study aim to test, in a randomized fashion, the hypothesis that early tapering of biologic agents (i.e.
increasing the intervals between injections as soon as inactive disease is documented) is safe and non-inferior to the maintenance of stable treatment intensity over 24 weeks, and therefore test the possibility of early biologic agent withdrawal.
It will also study concentrations of different biological agent, the occurrence of anti-drugs antibodies while tapering and then withdrawing biologics, and their possible association with a higher risk of relapse.
In addition, investigators will test if the serum level of proteins 100 (MRP8/14) could be predictive of flares.
Finally, pharmaco-economic analyses and quality of life studies will be conducted.
Study Type
Interventional
Enrollment (Actual)
62
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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Paris, France, 75015
- Necker Children's Hospital
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
2 years to 17 years (CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patient aged 2 to 17 years and treated with etanercept or tocilizumab or adalimumab, or patient aged 6 to 17 years and treated with abatacept.
- Patient with an oligoarticular or polyarticular rheumatoid factor negative JIA
- Patient treated with biologic treatment for persistent arthritis according to the marketing authorization.
- Patient who achieved inactive disease within two years of treatment with the last biologic agent administered, according to Wallace criteria : no joints with active arthritis, no active uveitis (as defined by the SUN Working Group), ESR or CRP level within normal limits in the laboratory where tested (or, if elevated, not attributable to JIA), physician's global assessment of disease activity score (< 10/100 visual analogue scale), and duration of morning stiffness < ou = 15 minutes (within 7 days before the visit).
- Patient with inactive disease achieved for less than 12 months.
- Patient with stable doses of non-steroidal anti-inflammatory drugs, Methotrexate (maximum 20 mg/m2/week), and other non biologic DMARD for at least one month before inclusion
- Patient without steroids or joint injection or live vaccines injection for at least one month.
- Signed informed consent by both parents (or legal guardian) and patient's agreement.
- Patient affiliated to the National Health Assurance system.
Exclusion Criteria:
- Patient with systemic form, rheumatoid factor positive, psoriatic or associated with enthesitis related JIA.
- Patient undergoing biologic therapy due to JIA-associated uveitis or with active uveitis at time of randomization.
- Patient with any contraindication to continue ongoing biologic treatment, notably ongoing uncontrolled infection, suspicion or evidence of demyelinating disease of the central nervous system.
- Patient previously treated with the same biotherapy for which dose decreasing or biotherapy withdrawal was already tested in the past for inactive disease and then reintroduced.
- Pregnancy or absence of effective contraception (including abstinence) in a pubertal patient.
- Patient suffering from tuberculosis.
- Patient with moderate to severe cardiac failure (NYHA class III / IV).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: FACTORIAL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Experimental
|
will be tapered from every week to every 2 weeks for 12 weeks then to every 3 weeks for 12 weeks
Other Names:
will be tapered from every 2 weeks to every 3 weeks for 12 weeks and to every 4 weeks for 12 weeks
Other Names:
will be tapered from every 4 weeks to every 6 weeks for 24 weeks
Other Names:
will be tapered from every 4 weeks to every 6 weeks for 24 weeks
Other Names:
|
ACTIVE_COMPARATOR: Control
|
will be tapered from every week to every 2 weeks for 12 weeks then to every 3 weeks for 12 weeks
Other Names:
will be tapered from every 2 weeks to every 3 weeks for 12 weeks and to every 4 weeks for 12 weeks
Other Names:
will be tapered from every 4 weeks to every 6 weeks for 24 weeks
Other Names:
will be tapered from every 4 weeks to every 6 weeks for 24 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Persistence of inactive disease
Time Frame: 24 weeks
|
Inactive disease is defined by the criterion of Wallace :
For all the visits, joint counts and physician global assessment of disease activity will be performed by an investigator blinded from patient study group. |
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse and serious adverse events or of special interest
Time Frame: Weeks 12, 24, 36, 48, 60, 72
|
Weeks 12, 24, 36, 48, 60, 72
|
|
Persistent inactive disease as defined by Wallace criteria
Time Frame: 72 weeks
|
72 weeks
|
|
Juvenile Arthritis Disease Activity Score (JADA score)
Time Frame: Day 0, Weeks 12, 24, 48, 72
|
Day 0, Weeks 12, 24, 48, 72
|
|
Biological agent concentrations
Time Frame: Day 0, weeks 12, 24, 36, 48, 60
|
according to drug administration (Etanercept or Abatacept or Tocilizumab or Adalimumab)
|
Day 0, weeks 12, 24, 36, 48, 60
|
Anti-drugs antibodies concentrations
Time Frame: Day 0, weeks 12, 24, 36, 48, 60
|
anti-Etanercept or anti-Abatacept or anti-Tocilizumab or anti-Adalimumab
|
Day 0, weeks 12, 24, 36, 48, 60
|
Proteins S100 concentrations (MRP8/14 level)
Time Frame: Day 0, weeks 24, 48, 72
|
Day 0, weeks 24, 48, 72
|
|
Concentration of additional informative markers (cytokines, chemokines)
Time Frame: Day 0, weeks 24, 48, 72
|
Day 0, weeks 24, 48, 72
|
|
score of quality of life with the Paediatric Quality of Life (PedsQL)
Time Frame: Day 0, weeks 24, 36, 72
|
Day 0, weeks 24, 36, 72
|
|
score of quality of life with the Childhood Health Assessment Questionnaire (CHAQ)
Time Frame: Day 0, weeks 12, 24, 36, 72
|
Day 0, weeks 12, 24, 36, 72
|
|
score of quality of life with the Life Quality Questionnaire related to the health (EQ-5D Y)
Time Frame: Day 0, weeks 24, 36, 72
|
Day 0, weeks 24, 36, 72
|
|
cost of early treatment tapering and withdrawal
Time Frame: weeks 12, 24, 36, 60, 72
|
weeks 12, 24, 36, 60, 72
|
|
cost of late treatment tapering and withdrawal
Time Frame: weeks 12, 24, 36, 60, 72
|
weeks 12, 24, 36, 60, 72
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Chair: Florence UETTWILLER, PhD, Necker Children's Hospital, Paris, France
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
May 18, 2017
Primary Completion (ACTUAL)
October 29, 2019
Study Completion (ACTUAL)
October 1, 2020
Study Registration Dates
First Submitted
July 19, 2016
First Submitted That Met QC Criteria
July 20, 2016
First Posted (ESTIMATE)
July 21, 2016
Study Record Updates
Last Update Posted (ACTUAL)
April 1, 2021
Last Update Submitted That Met QC Criteria
March 31, 2021
Last Verified
March 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Arthritis
- Arthritis, Juvenile
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gastrointestinal Agents
- Immune Checkpoint Inhibitors
- Etanercept
- Adalimumab
- Abatacept
Other Study ID Numbers
- P 150902
- 2016-000312-15 (EUDRACT_NUMBER)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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