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Oligoarthritis, JuvenilePhase 3STARSNCT03728478

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

A Phase 3 study testing Etanercept, Methotrexate and Intra-articular corticosteroid injections in people with Oligoarthritis, Juvenile and Polyarthritis, Juvenile, Rheumatoid Factor Negative, run by Istituto Giannina Gaslini at 1 site in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 2 to 17 years
What is being tested?
Etanercept, Methotrexate and Intra-articular corticosteroid injections
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
260 participants
Where
1 siteItaly
Study dates
29 May 2019to 28 Feb 2025
Phase
Phase 3
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 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Each patient must meet all the following criteria in order to be enrolled in the trial:
  • 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:
  • Oligoarthritis ii. Rheumatoid factor negative polyarthritis
  • Active arthritis
  • Onset of JIA symptoms no more than 6 months before randomization
  • Age 2 to 17 years at enrolment.
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  • 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.
  • 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
  • Duly executed, written, informed consent/assent obtained from the parents/patient.

Who cannot join

  • Classification in one of the following JIA categories: systemic arthritis, RF-positive polyarthritis, psoriatic arthritis, enthesitis-related arthritis, undifferentiated arthritis
  • Patients who need systemic treatment for uveitis
  • Tuberculosis related issues: patients are excluded from the study if they have:
  • Active TB or a history of incompletely treated TB
  • 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.
  • Suspected extrapulmonary TB infection
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  • Patients at high risk of contracting TB, such as close contact with individual with active or latent TB
  • Previous treatment with any synthetic or biologic DMARD
  • 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
  • Prior or current history of malignancy or any other significant concomitant illness(es) as per the treating physician evaluation
  • Any of the following laboratory abnormalities based on the most recent laboratory results:
  • White blood cell (WBC) count <3.50 x 103/mm3 (SI units: <3.50 x 109/L) and neutrophils < 1x109/L;
  • Hemoglobin < 8.5 g/dL (SI units: <85 g/L);
  • Platelet Count < 125,0000/mm3 or ≥1,000,000/mm3 (SI units: <125 x 109/L or ≥1,000 x 109/L
  • Aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT) ≥ 2.0 x upper limit of normal (ULN).

Trial locations and contacts

1 site in 1 country.

Alessandro Consolaro, MD, PhD contact

01056362729

alessandroconsolaro@gaslini.org

Italy1 site, 1 recruiting

  • IRCCS Istituto Giannina Gaslini

    Genova, GE, 16147

    Alessandro Consolaro, MD, +39 01056362729, alessandroconsolaro@gaslini.org

    Recruiting

Other trials in Italy

About this study

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

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).

Read the detailed description

Although their approach is different, both interventions are aimed to obtain a quick and robust disease control and to maintain it over time. Compelling evidence exists that in children with chronic arthritis early intensive therapy may take advantage of the so-called "window of opportunity", in which the biology of the disease can be altered to improve long-term disease outcomes, including prevention of cumulative joint damage. Recent experiences in children with systemic JIA have shown that early anti-IL-1 therapy may lead to rapid achievement of inactive disease and allow early treatment discontinuation without disease relapses in many patients. The benefits of early treatment with biologic agents in other JIA categories are less clear, but convincing evidence has been recently reported for polyarthritis.

Being tested
Etanercept, Methotrexate, Intra-articular corticosteroid injections
Keywords
juvenile idiopathic arthritis, treatment, treat to target
Medical subject headings
Arthritis, Juvenile

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EtanerceptDrug

    Also called ETN

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

  • MethotrexateDrug

    Also called MTX

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

  • Intra-articular corticosteroid injectionsDrug

    Also called IACI

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

Study groups in NCT03728478
Study groupRoleWhat they receive
Treatment arm 1: Step-upNo interventionJIA patients managed with a Treat-To-Target strategy (T2T)
Treatment arm 2: Step-downExperimentalJIA patients treated with an early combined therapy
Receives: Drug: Etanercept; Drug: Methotrexate; Drug: Intra-articular corticosteroid injections

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical remission on or off medication at 12 months

    The effectiveness of the two therapeutic strategies will be compared by assessing the frequency of clinical remission (CR) at 12 months. CR is defined as the persistence of the JADAS state of ID for at least 6 months.

    Measured: 12 months

Secondary outcomes (8)

  1. 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.

    Measured: 12 months

  2. Time to inactive disease as per JADAS/JIA ACR criteria

    Time to achieve the state of JADAS/JIA ACR 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.

    Measured: 12 months

  3. Time to JADAS/JIA ACR clinical remission

    Time to achieve the state of JADAS/JIA ACR 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 clinical remission (i.e. persistent inactive disease for at least 6 months).

    Measured: 12 months

  4. Time spent in JADAS/JIA ACR inactive disease

    The cumulative time spent in the JADAS/JIA ACR state of ID will be calculated as the time difference (in days) between the date of the first visit at which the patient will be observed to be in ID and the date at which he/she will be observed to be no longer in ID that is when the disease will flare (see later for definitions), or database closure for analysis purposes. We will assume that if a patient is found to be in ID at 2 consecutive visits, the patient had ID on all days between these visits. If a patient will be found to have ID at a particular visit, but lost the ID status at the subsequent visit, the patient will be considered to have been in ID until the recurrence of active disease. Patients found to be in ID only at the time of database closure will contribute a single day of ID. The time in inactive disease per patient will be recorded and compared between the 2 arms.

    Measured: 12 months

  5. Cumulative level of disease activity throughout the study period

    The area under the curve (AUC) of the JADAS10 score assessed at every study visit and the AUC of the parent version of the JADAS (parJADAS) assessed monthly will be recorded and compared between the 2 arms.

    Measured: 12 months

  6. Time spent on therapy

    The cumulative time on therapy will be calculated as the time difference (in days) between the date of the visit at which the patient will start a systemic medication (synthetic or biologic DMARDs or steroids) until the date at which he/she will be observed to no longer be in treatment with a systemic medication, or completed the study. We assume that if a patient does not receive medications at 2 consecutive visits, the patient had not received medications all days between these visits. Patients initiating a systemic treatment at the final visit of the study will contribute a single day of time in therapy. The mean percentage of time spent on therapy per patient will be recorded and compared between the 2 arms.

    Measured: 12 months

  7. Rate of flares

    The rate of patients who develop flare, defined as the recurrence of active disease after attaining inactive disease at last visit according JADAS or JIA ACR definition, and the number of flares and the time to flare per patient will be recorded and compared. Notably, all patients prescribed intra-articular injections, synthetic or biologic DMARDs or systemic steroids will be considered as flare independently from JADAS or ACR criteria.

    Measured: 12 months

  8. Rate of uveitis onset

    The rate of patients who develop uveitis according to the Standardized Uveitis Nomenclature (SUN) will be recorded and compared between the 2 arms. The rate of patients requiring systemic medications for treatment of uveitis will be also recorded and compared between the 2 arms. However, these patients will be excluded from the study and followed for safety only.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Nov 2018
  2. Study start29 May 2019
  3. Primary completion28 Feb 2025 (estimated)
  4. Study completion28 Feb 2025 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a a 12-month open label, randomised, actively controlled, multi-centre, prospective, superiority trial of two different treatment strategies (Step-down versus Step-up). After signature of informed consent/assent patients will be randomized into two therapeutic arms: "Step-up" or "Step-down". Patients in the Step-up arm will be treated according to a conventional strategy based on treatment escalation and driven by the treat-to-target strategy. Patients in the Step-Down arm will be treated with an early, combined, aggressive therapy for 6 months. After the conclusion of the 12-month observation period of the trial, patients will be followed for up to 5 years for the evaluation of disease course, medication requirements, adverse events, and long-term disease-related morbidity.
Masking
None (open label)
Enrolment
260 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03728478
Sponsor's protocol ID
2018-001931-27
Other IDs
2018
Acronym
STARS
Status last verified
Oct 2024
First submitted
31 Oct 2018
Last updated
15 Oct 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Wallace CA, Giannini EH, Spalding SJ, Hashkes PJ, O'Neil KM, Zeft AS, Szer IS, Ringold S, Brunner HI, Schanberg LE, Sundel RP, Milojevic D, Punaro MG, Chira P, Gottlieb BS, Higgins GC, Ilowite NT, Kimura Y, Hamilton S, Johnson A, Huang B, Lovell DJ; Childhood Arthritis and Rheumatology Research Alliance. Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis. Arthritis Rheum. 2012 Jun;64(6):2012-21. doi: 10.1002/art.34343. Epub 2011 Dec 19.

    PubMed 22183975

  • Ravelli A, Consolaro A, Horneff G, Laxer RM, Lovell DJ, Wulffraat NM, Akikusa JD, Al-Mayouf SM, Anton J, Avcin T, Berard RA, Beresford MW, Burgos-Vargas R, Cimaz R, De Benedetti F, Demirkaya E, Foell D, Itoh Y, Lahdenne P, Morgan EM, Quartier P, Ruperto N, Russo R, Saad-Magalhaes C, Sawhney S, Scott C, Shenoi S, Swart JF, Uziel Y, Vastert SJ, Smolen JS. Treating juvenile idiopathic arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2018 Jun;77(6):819-828. doi: 10.1136/annrheumdis-2018-213030. Epub 2018 Apr 11.

    PubMed 29643108

  • Tan J, Renton WD, Whittle SL, Takken T, Johnston RV, Tiller G, Munro J, Buchbinder R. Methotrexate for juvenile idiopathic arthritis. Cochrane Database Syst Rev. 2024 Feb 9;2(2):CD003129. doi: 10.1002/14651858.CD003129.pub2.

    PubMed 38334147

  • Burrone M, Mazzoni M, Naddei R, Pistorio A, Spelta M, Scala S, Patrone E, Garrone M, Lombardi M, Villa L, Pascale G, Cavanna R, Ruperto N, Ravelli A, Consolaro A; Paediatric Rheumatology International Trials Organisation (PRINTO). Looking for the best strategy to treat children with new onset juvenile idiopathic arthritis: presentation of the "comparison of STep-up and step-down therapeutic strategies in childhood ARthritiS" (STARS) trial. Pediatr Rheumatol Online J. 2022 Sep 7;20(1):80. doi: 10.1186/s12969-022-00739-x.

    PubMed 36071444

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Etanercept, Methotrexate and Intra-articular corticosteroid injections in people with Oligoarthritis, Juvenile and Polyarthritis, Juvenile, Rheumatoid Factor Negative, run by Istituto Giannina Gaslini at 1 site in Italy.

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 9 inclusion and 15 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 15 Oct 2024. 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 Italy. 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Contact Alessandro Consolaro, MD, PhD (01056362729, alessandroconsolaro@gaslini.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical remission on or off medication at 12 months (time frame: 12 months). 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 NCT03728478, which also lists 4 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 15 Oct 2024.

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