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

NCT03728478 | Recruiting Phase 3

• 1 other identifier: 2018-001931-27
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 1

Brief 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 strategy).

Conditions

Oligoarthritis, Juvenile; Polyarthritis, Juvenile, Rheumatoid Factor Negative

Keywords

juvenile idiopathic arthritis; treatment; treat to target

Outcome Measures

Primary Outcomes (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.

  12 months

Secondary Outcomes (8)

• Inactive disease

  12 months

• Time to inactive disease as per JADAS/JIA ACR criteria

  12 months

• Time to JADAS/JIA ACR clinical remission

  12 months

• Time spent in JADAS/JIA ACR inactive disease

  12 months

• Cumulative level of disease activity throughout the study period

  12 months

Study Arms (2)

Treatment arm 1: Step-up

NO INTERVENTION

JIA patients managed with a Treat-To-Target strategy (T2T)

Treatment arm 2: Step-down

EXPERIMENTAL

JIA patients treated with an early combined therapy

Drug: Etanercept; Drug: Methotrexate; Drug: Intra-articular corticosteroid injections

Interventions

Etanercept DRUG

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

Also known as: ETN

Treatment arm 2: Step-down

Methotrexate DRUG

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

Also known as: MTX

Treatment arm 2: Step-down

Intra-articular corticosteroid injections DRUG

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

Also known as: IACI

Treatment arm 2: Step-down

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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
• 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:
• 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).

Sponsors & Collaborators

• Istituto Giannina Gaslini: lead
• Agenzia Italiana del Farmaco: collaborator
• Compagnia di San Paolo: collaborator
• Pfizer: collaborator

Study Sites (1)

IRCCS Istituto Giannina Gaslini

Genova, GE, 16147, Italy

RECRUITING

Related Publications (4)

• 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.

  PMID: 22183975 BACKGROUND

• 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.

  PMID: 29643108 BACKGROUND

• 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.

  PMID: 38334147 DERIVED

• 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.

  PMID: 36071444 DERIVED

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

Etanercept; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Alessandro Consolaro, MD, PhD

CONTACT

01056362729; alessandroconsolaro@gaslini.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: October 31, 2018
• First Posted: November 2, 2018
• Study Start: May 29, 2019
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)