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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 3INTERVENTIONAL

STep-up and Step-down Therapeutic Strategies in Childhood ARthritiS

Comparison of STep-up and Step-down Therapeutic Strategies in Childhood ARthritiS

STep-up and Step-down Therapeutic Strategies in Childhood ARthritiS (NCT03728478) is a Phase 3 interventional studying Oligoarthritis, Juvenile and Polyarthritis, Juvenile, Rheumatoid Factor Negative, sponsored by Istituto Giannina Gaslini. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

This study aims 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 the initial start of a combination of conventional and biological DMARDs (step-down strategy).

What Stage of Research Is This?

Phase 3 trials confirm efficacy and safety in large patient groups (often 300–3,000+) and form the evidence base for an FDA approval submission. For Oligoarthritis, Juvenile, Phase 3 studies typically randomize participants between the investigational treatment and either a placebo or current standard of care. A successful Phase 3 result is the threshold most treatments need to clear before regulatory approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 260 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Oligoarthritis, Juvenile subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Inclusion Criteria Each patient must meet all the following criteria in order to be enrolled in the trial: 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. If sexually active, they must agree to use highly effective contraceptive measures, 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 highly effective contraceptive measures if sexually active. VI. Ability to comply with the entire study procedures, ability to communicate meaningfully with the investigational staff, competence to give written willing to sign a consent form; to be applied to the parents and/or patients, as appropriate VII. Duly executed, written, willing to sign a consent form/assent obtained from the parents/patient. 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: 1. Active TB or a history of incompletely treated TB ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria Each patient must meet all the following criteria in order to be enrolled in the trial: 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. If sexually active, they must agree to use highly effective contraceptive measures, 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 highly effective contraceptive measures 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. 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: 1. Active TB or a history of incompletely treated TB 2. 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. 3. Suspected extrapulmonary TB infection 4. 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 VII. Any of the following laboratory abnormalities based on the most recent laboratory results: 1. White blood cell (WBC) count \<3.50 x 103/mm3 (SI units: \<3.50 x 109/L) and neutrophils \< 1x109/L; 2. Hemoglobin \< 8.5 g/dL (SI units: \<85 g/L); 3. Platelet Count \< 125,0000/mm3 or ≥1,000,000/mm3 (SI units: \<125 x 109/L or ≥1,000 x 109/L 4. Aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT) ≥ 2.0 x upper limit of normal (ULN).

Treatments Being Tested

DRUG

Etanercept

Patients will receive etanercept subcutaneously at a dose of 0.8 mg/kg weekly (up to a maximum dose of 50 mg weekly).

DRUG

Methotrexate

Methotrexate will be administered subcutaneously, in a single weekly dose of 15 mg/m2 (max 20 mg).

DRUG

Intra-articular corticosteroid injections

Triamcinolone hexacetonide and methylprednisolone acetate doses depend on the affected joint.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

IRCCS Istituto Giannina Gaslini
Genova, GE, Italy

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT03728478), the sponsor (Istituto Giannina Gaslini), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT03728478 clinical trial studying?

This study aims 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 the initial start of a combination of conventional and biological DMARDs (step-down strategy). The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT03728478?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT03728478?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT03728478. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT03728478. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.