Juvenile idiopathic arthritis (JIA) is an umbrella term that encompasses a heterogeneous group of disorders characterised by prolonged synovial inflammation that may cause destructive damage to joint structures. Permanent changes may also develop in extraarticular organs, particularly the eye (as a complication of chronic anterior uveitis), or may result from side effects of medications. MedDRA version: 20.0 Level: LLT Classification code 10059177 Term: Juvenile arthritis System Organ Class: 10
Conditions
Interventions
Trade Name: Reumaflex
Pharmaceutical Form: Solution for infusion in pre-filled syringe
INN or Proposed INN: METHOTREXATE
CAS Number: 59-05-2
Current Sponsor code: METHOTREXATE
Other descriptive name:
Sponsors
IRCCS Istituto Giannina Gaslini
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I. Newly-diagnosed and synthetic or biologic DMARD-naïve children (only treatment with 1 NSAID is allowed and no corticosteroid joint injections prior to randomization ) with a JIA classified according to the following ILAR categories: i. Oligoarthritis ii. Rheumatoid factor negative polyarthritis II. Active arthritis III. Onset of JIA symptoms no more than 6 months before randomization IV. Age 2 to 17 years at enrolment. V. Female of child-bearing potential must have a negative pregnancy test at the beginning of the trial, and then every 3 months. If sexually active, they must agree to use adequate contraception, throughout study participation, and must have no intention of conceiving during the course of the study. Post-pubertal males must have no plans to father a child during the study and agree to use adequate birth control methods if sexually active. VI. Ability to comply with the entire study procedures, ability to communicate meaningfully with the investigational staff, competence to give written informed consent; to be applied to the parents and/or patients, as appropriate VII. Duly executed, written, informed consent/assent obtained from the parents/patient. Are the trial subjects under 18? yes Number of subjects for this age range: 260 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: I. Classification in one of the following JIA categories: systemic arthritis, RF-positive polyarthritis, psoriatic arthritis, enthesitis-related arthritis, undifferentiated arthritis II. Patients who need systemic treatment for uveitis III. Tuberculosis related issues: patients are excluded from the study if they have: a. Active TB or a history of incompletely treated TB b. PPD or QuantiFERON-TB positive patients (with no active disease) unless it is documented by a specialist that the patient has been adequately treated for TB and can start treatment with a biologic agent, based on the medical judgment of the study investigator and / or an infectious disease specialist. c. Suspected extrapulmonary TB infection d. Patients at high risk of contracting TB, such as close contact with individual with active or latent TB IV. Previous treatment with any synthetic or biologic DMARD V. Any live attenuated vaccine within 4 weeks prior to the baseline visit, such as varicella-zoster, oral polio, measles, mumps or rubella vaccines and throughout the study. Killed or inactive vaccine may be permitted based on the investigator’s judgment VI. Prior or current history of malignancy or any other significant concomitant illness(es) as per the treating physician evaluation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The study is aimed to compare the effectiveness of a conventional therapeutic regimen, based on treatment escalation (Step-up strategy) and driven by the treat-to-target approach, with that of an early aggressive intervention based on a combination of conventional and biological DMARDs (Step-down strategy). The hypothesis tested in this trial is whether an early aggressive therapy with a 6-month course of an anti-TNF agent in combination with methotrexate or with methotrexate alone in the milder forms of oligoarthritis (Step-down arm) is more effective in inducing clinical remission on medication (i.e. at least 6-month of continuous inactive disease while receiving anti-rheumatic medications) than a conventional therapeutic approach based on treatment escalation (Step-up arm), which efficacy is maximized through the implementation of a treat-to-target approach ;Secondary Objective: •Inactive disease The rate of patients who achieve the JADAS/JIA ACR state of ID at any single point in time throughout the study period will be compared between the 2 arms. •Time to inactive disease as per JADAS/JIA ACR criteria Time to achieve the JADAS/JIA ACR state of ID will be calculated as the time difference (in days) between the date of randomization and the date of the visit at which the patient will be observed to be in ID. •Time to JADAS/JIA ACR clinical remission Time to achieve the JADAS/JIA ACR state of clinical remission will be calculated as the time difference (in days) between the date of randomization and the date of the visit at which the patient will be observed to be in clinical remission (i.e. persistent inactive disease for at least 6 months). ;Primary end point(s): •Inactive disease The rate of patients who achieve the JADAS/JIA ACR state of ID at any single point in time throughout the study period will be compared between the 2 arms. •Time to inactive disease as per JADAS/JIA ACR criteria Time to achieve the JADAS/JIA ACR state of ID will be c | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Inactive disease • Time to inactive disease as per JADAS/JIA ACR criteria • Time to JADAS/JIA ACR clinical remission • Time spent in JADAS/JIA ACR inactive disease;Timepoint(s) of evaluation of this end point: Patients will be evaluated at 3, 6, 9, 12 months after enrollment. | — |
Countries
Italy
Contacts
Public ContactPRINTO
PRINTO
Outcome results
None listed