| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with oligoarticular onset or rheumatoid factor negative polyarticular JIA followed in tertiary care center for paediatric rheumatology. |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10059176 |
| E.1.2 | Term | Juvenile idiopathic arthritis |
| E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Primary objective
Demonstrate the non inferiority of a strategy of early tapering of biological agent, compared to the maintenance of stable treatment intensity over 24 weeks after reaching inactive disease.
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| E.2.2 | Secondary objectives of the trial |
To assess safety at each visit, every 12 weeks until Week 72.-To compare the rate of persistent clinical remission with an objective of non inferiority at Week 72 between the two groups To assess the JADAS score at each visit.-To determine at each visit, biological agent concentration, conduct pharmacokinetic analysis, and check anti-drug antibodies.-To constitute a DNA bank for further pharmacogenomic analysis.-To test the predictive value of proteins S100 concentrations regarding the risk of flare.-To assess and compare the score of quality of life in each group, assuming that early tapering of the treatments will be associated with better quality of life.-To estimate the cost, cost assuming a rate of adverse events and serious adverse events in our experimental group inferior or equal.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
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 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 one year of treatment with the last biologic agent administered, according to Wallace criteria : no joints with active arthritis, no active uveitis (the Standardization of Uveitis Nomenclature (SUN) Working Group defines inactive anterior uveitis as "grade zero cells," indicating_1 cell in field sizes of 1 mm by a 1-mm slit beam), 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 15 minutes (within 7 days before the visit).
- Patient with inactive disease achieved for less than 6 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.
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| E.4 | Principal exclusion criteria |
Exclusion criteria
- Patient with systemic form, rheumatoid factor positive, psoriatic or associated 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, ...
- Pregnancy or absence of effective contraception (including abstinence) in a pubertal patient
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary assessment criteria
The primary outcome is the persistence of inactive disease 24 weeks after randomization.
Inactive disease is defined by the criterion of Wallace 1 28:
- no joints with active arthritis,
- no active uveitis as defined by the SUN Working Group 2, (The Standardization of Uveitis Nomenclature (SUN) Working Group defines inactive anterior uveitis as "grade zero cells," indicating_1 cell in field sizes of 1 mm by a 1-mm slit beam),
- erythrocyte sedimentation rate (ESR) or C-reactive protein (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 15 minutes (within 7 days before the visit).
For all the visits, joint counts and physician global assessment of disease activity will be performed by an investigator blinded to patient study group.
Secondary assessment criteria
- Persistent inactive disease at W72 as defined by Wallace criteria.
- Adverse and serious adverse events and special interest at each time point.
- The JADAS at each time point (Juvenile Arthritis Disease Activity Score), which includes the child or parental assessment of disease activity.
- Biological agent and anti-drug antibodies concentrations at each time point during treatment and 12 weeks after the end of treatment.
- Pharmacogenomic analysis.
- Concentration of S100 proteins (MRP8/14) every 24 weeks.
- The scores of quality of life every 24 weeks with:
- The Paediatric Quality of Life Inventory 4.0 Generic Core Scale 29,
- The Childhood Health Assessment Questionnaire (CHAQ) 30 ,
- Life Quality Questionnaire related to the health (EQ-5D Y) 31.
-The cost of both strategies and economic evaluation of early withdrawal.
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 21 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
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