Juvenile Idiopathic Arthritis (JIA)Phase 4Re-JIANCT06618937
Toward Personalized Medicine to Guide Drug Withdrawal in Children with Juvenile Idiopathic Arthritis in Clinical Remission
A Phase 4 study testing Treatment medication withdrawal strategy in people with Juvenile Idiopathic Arthritis (JIA), run by Istituto Giannina Gaslini at 1 site in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Juvenile Idiopathic Arthritis (JIA)
- What is being tested?
- Treatment medication withdrawal strategy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 166 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jan 2025to 1 Jan 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- - 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.
Who cannot join
- - 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
Istituto Giannina Gaslini
Genoa, GE, 16147
Clara Malattia, MD, 0039 010 56362843, claramalattia@gaslini.org
About this study
Official title: Toward Personalized Medicine to Guide Drug Withdrawal in Children with Juvenile Idiopathic Arthritis in Clinical Remission: a Randomized Clinical Trial Comparing Early Versus Late Drug Withdrawal Combining Imaging and Multi-Omics
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.
Read the detailed description
The study is designed as a multicenter, prospective, randomized, open label superiority trial of two different treatment medication withdrawal strategies (early biomarkers-guided versus conventional unguided drugs withdrawal strategy). Musculoskeletal ultrasound (MSUS) and serum biomarkers, such as the S-100 protein family, allow a more accurate assessment of remission status than clinical evaluation alone. Subclinical synovitis detected by MSUS at the joint level and increased level of S100 proteins have been associated with an increased risk of loss of clinically inactive disease after drug discontinuation. The results of this study will provide a more rational approach to treatment withdrawal in inactive JIA patients. It is expected that a risk-adapted strategy would reduce both number of disease flares and cumulative drug exposure compared with standard-of-care practice. If validated, these biomarkers will help to personalize immunosuppressant withdrawal: a therapy paradigm shift while ensuring patient and economic benefits.
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 of serum biomarkers who are randomized in the intervention arm.
Blood samples for research laboratory analysis (multi Omics, characterization of immune cell populations and quantification of cytokines concentration and EV-miRNAs expression) will be collected at baseline, at drugs withdrawal and in case of disease flare.
- Conditions
- Juvenile Idiopathic Arthritis (JIA)
- Being tested
- Treatment medication withdrawal strategy
- Keywords
- JIA, imaging, omics, withdrawal
- Medical subject headings
- Arthritis, Juvenile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment medication withdrawal strategyOther
The study aims to compare early biomarkers-guided versus conventional unguided drugs withdrawal strategy.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (1)
Rate of flare
To compare rate and time to flare in the randomized arms. Disease flare is defined as any patient who will loose the status of inactive disease or has a clinical Juvenile Arthritis Disease Activity Score (cJADAS)10 \>1.5 or 2.5 for oligoarticular or polyarticular disease, respectively and prompt the caring physician to make a major therapeutic intervention that could include an intrarticular glucocorticoid injection, the start of systemic glucocorticoid therapy, the restart of cs/b/ts-DMARDs at the conventional regimen.
Frequencies of flares will be analyzed in both study arms and will be compared by means of the Chi-square test or the Fisher's exact test whenever appropriate. Bionomial exact 95% confidence interval will be also computed and reported.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2024
- Study start1 Jan 2025 (estimated)
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Juvenile Idiopathic Arthritis (JIA)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 166 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Giannina Gaslini
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nicolino Ruperto, MD, MPH, Istituto Giannina Gaslini
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06618937
- Sponsor's protocol ID
- 2024-514732-24-00
- Acronym
- Re-JIA
- Status last verified
- Sep 2024
- First submitted
- 25 Sep 2024
- Last updated
- 1 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Toward Personalized Medicine to Guide Drug Withdrawal in Children with Juvenile Idiopathic Arthritis in Clinical Remission: a Randomized Clinical Trial Comparing Early Versus Late Drug Withdrawal Combining Imaging and Multi-Omics
- ClinicalTrials.gov ID
- NCT06618937
- Acronym / sponsor ID
- Re-JIA / 2024-514732-24-00
- Conditions
- Juvenile Idiopathic Arthritis (JIA)
- Keywords
- JIA, imaging, omics, withdrawal
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 166 participants (estimated)
- Lead sponsor
- Istituto Giannina GasliniUniversity, hospital or other
- Study start
- 1 Jan 2025 (estimated)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2029 (estimated)
- First posted
- 1 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study is designed as a multicenter, prospective, randomized, open label superiority trial of two different treatment medication withdrawal strategies (early biomarkers-guided versus conventional unguided drugs withdrawal strategy). Musculoskeletal ultrasound (MSUS) and serum biomarkers, such as the S-100 protein family, allow a more accurate assessment of remission status than clinical evaluation alone. Subclinical synovitis detected by MSUS at the joint level and increased level of S100 proteins have been associated with an increased risk of loss of clinically inactive disease after drug discontinuation. The results of this study will provide a more rational approach to treatment withdrawal in inactive JIA patients. It is expected that a risk-adapted strategy would reduce both number of disease flares and cumulative drug exposure compared with standard-of-care practice. If validated, these biomarkers will help to personalize immunosuppressant withdrawal: a therapy paradigm shift while ensuring patient and economic benefits.
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 of serum biomarkers who are randomized in the intervention arm.
Blood samples for research laboratory analysis (multi Omics, characterization of immune cell populations and quantification of cytokines concentration and EV-miRNAs expression) will be collected at baseline, at drugs withdrawal and in case of disease flare.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Biomarker-guided drug withdrawal | Experimental | Other: Treatment medication withdrawal strategyPatients 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 |
| 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. |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- - 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
Key exclusion criteria (8 listed)
- - 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treatment medication withdrawal strategyThe study aims to compare early biomarkers-guided versus conventional unguided drugs withdrawal strategy. | Other | Biomarker-guided drug withdrawal |
Primary outcome
Effectiveness of early biomarker-guided withdrawal of antirheumatic agents
Time frame: 12 months
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.
1 secondary outcome
Rate of flare
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Treatment medication withdrawal strategy in people with Juvenile Idiopathic Arthritis (JIA), 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 6 inclusion and 8 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: opening soon, as of the sponsor's last update on 1 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clara Malattia, MD (0039 01056362843, claramalattia@gaslini.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effectiveness of early biomarker-guided withdrawal of antirheumatic agents (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Oct 2024.