Toward Personalized Medicine to Guide Drug Withdrawal in Children with Juvenile Idiopathic Arthritis in Clinical Remission

NCT06618937 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 2024-514732-24-00
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 1

Brief Summary

Biologic therapies made clinical remission an achievable goal for most juvenile idiopathic arthritis (JIA) patients. Nevertheless, antirheumatic drugs have side effects and are costly. Currently, no guidelines exist for withdrawing drugs in JIA patients with clinical inactive disease (CID). Relapses following the withdrawal of antirheumatic drugs are common. To establish an optimal timeline for treatment discontinuation is a major unmet need in pediatric rheumatology. It is hypothesized that biomarkers-guided early withdrawal of antirheumatic drugs in patients achieving clinical, imaging and biological remission is safe and more effective compared to the standard practice of maintenance of stable treatment over 12 months.

Conditions

Juvenile Idiopathic Arthritis (JIA)

Keywords

JIA; imaging; omics; withdrawal

Outcome Measures

Primary Outcomes (1)

• Effectiveness of early biomarker-guided withdrawal of antirheumatic agents

  At each timepoint the following procedures will be performed: joint assessment, Physician's Global Assessment of Overall Disease Activity, JAMAR, Uveitis assessment (in ANA positive patients), Hematology, chemistry, CRP, ESR, urine analysis according to drug specific schedule and Good Clinical Practice (GCP). Drug Adverse Events will be collected (MedDRA), to measure safety and efficacy of early biomarker-guided withdrawal of antirheumatic agents in JIA patients achieving 6 months clinical inactive disease (CID) who do not have subclinical inflammation when compared to the standard practice of maintenance of stable treatment intensity over 12 months.

  12 months

Secondary Outcomes (1)

• Rate of flare

  24 months

Study Arms (2)

Biomarker-guided drug withdrawal

EXPERIMENTAL

Patients with inactive disease, absence of sublinical synovitis at the joint level and normal S100A8/9 and hs-CRP leves will be randomly assigned to either an early biomarker-guided drug withdrawal protocol (interventional arm) or continuation of ongoing therapy at unchanged dose for an additional 6 months and then gradual tapering (control arm). Patients will be evaluated at baseline, then every 3 months if still on treatment and every 6 months after drug withdrawal. At each timepoint the following procedures will be performed: joint assessment, Physician's Global Assessment of Overall Disease Activity, JAMAR, Uveitis assessment (in ANA positive patients), Hematology, chemistry, CRP, ESR, urine analysis according to drug specific schedule and Good Clinical Practice (GCP). Drug Adverse Events will be collected (MedDRA). MSUS and serum biomarkers quantification (S100A8/9, hs-CRP) will be repeated every 3 months until month 18 in patients with subclinical synovitis and pathologic values

Other: Treatment medication withdrawal strategy

Gradual tapering

NO INTERVENTION

The control arm will continue ongoing therapy at unchanged dose for an additional 6 months and then will gradually taper the therapy.

Interventions

Treatment medication withdrawal strategy OTHER

The study aims to compare early biomarkers-guided versus conventional unguided drugs withdrawal strategy.

Biomarker-guided drug withdrawal

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \- Children with a diagnosis of JIA according to the ILAR classification criteria
• JIA patients who satisfy criteria for inactive disease for a minimum of 6 continuous months while still taking medication.
• Patients who have been treated with cs/b/bs/ts DMARDs according to the label indication
• 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 obtained from the patient's parents/legal guardian
• Female of child-bearing potential must have a negative pregnancy test at the beginning of the trial. If sexually active, they must have no intention of conceiving while on treatment with antirheumatic drugs.

You may not qualify if:

• \- Patients with systemic JIA according to ILAR criteria
• Patients with undifferentiated arthritis according to ILAR criteria
• Patients with severe disease-related ocular damage and who need systemic treatment for uveitis
• Patients who received glucocorticoid treatment 3 months prior to baseline visit
• Patients who had previously unsuccessfully attempted tapering cs/b/bs/tsDMARDs
• Patients with severe damage as per caring physician measured
• Prior or current history of other significant concomitant illness(es) that, according to the Investigator's judgment, would adversely affect the patient's participation in the study
• Any other medical condition or laboratory examination which in the opinion of the caring physician should exclude the patient from participation to the study

Sponsors & Collaborators

• Istituto Giannina Gaslini: lead

Study Sites (1)

Istituto Giannina Gaslini

Genoa, GE, 16147, Italy

Location

MeSH Terms

Conditions

Arthritis, Juvenile

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Clara Malattia, MD

CONTACT

0039 01056362843; claramalattia@gaslini.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Trial Centre Director

Study Record Dates

• First Submitted: September 25, 2024
• First Posted: October 1, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)