Preventing Extension of Oligoarticular Juvenile Idiopathic Arthritis JIA (Limit-JIA)

Study Overview
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Brief Summary
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This is a research study to test whether a once-weekly injection of abatacept will prevent the progression of Juvenile Idiopathic Arthritis (JIA) to a more severe form. To evaluate the effectiveness of a 24-week course of treatment with abatacept plus usual care versus usual care to prevent polyarthritis (≥5 joints), uveitis, or treatment with other systemic medication within 18 months of randomization in children with recent-onset limited JIA.

Detailed Description
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Part I enrolled participants into a randomized open-label multicenter trial with a planned sample size of 306 JIA participants recruited from CARRA Registry sites. Participants were randomly allocated (1:1) to receive 24 weeks of abatacept plus usual care or usual care alone. Upon completion of 24 weeks of randomized treatment, each participant was to receive usual care and undergo follow-up for assessment of outcomes for an additional 12 months. Planned duration of the study for each participant was 18 months. Due to slow accrual and apparent loss of equipoise, enrollment into Part I has been discontinued 17February2022 As of October 29, 2021, 39 participants have been randomized in Part I. Part I participants will continue follow-up as planned. Part II is a non-randomized continuation of LIMIT-JIA with planned enrollment of 89 to reach 80 evaluable participants receiving to the abatacept arm. Participants will now receive 24 doses of abatacept plus usual care. Upon completion of 24 doses of treatment, each participant will receive usual care and undergo follow-up for assessment of outcomes for an additional 6 months. Planned duration of the study for each participant is 12 months. Part II will assess the efficacy of abatacept in prevention of disease extension by comparison of outcomes between participants enrolled in the abatacept arm and 428 CARRA Registry patients who would have met major eligibility criteria for LIMIT-JIA.

Official Title
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An Open Label, Multi-Center, Phase 3 Efficacy Study of Sub-Q Abatacept in Preventing Extension of Oligoarticular Juvenile Idiopathic Arthritis JIA (Limit-JIA)

Conditions
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Juvenile Idiopathic Arthritis

Intervention / Treatment
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* Drug: Abatacept Injection
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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To be eligible for this trial, participants must meet all of the following criteria in order to be include in the study: Age ≥ 2 years old and ≤16.5 years old Clinical diagnosis of JIA by a pediatric rheumatologist within the past 6 months Arthritis affecting ≤4 joints between disease onset and enrollment Enrollment in the CARRA Registry Participants of childbearing potential must agree to remain abstinent or agree to use an effective and medically acceptable form of birth control from the time of written or verbal assent to at least 66 days after taking the last dose of study drug. Weight ≥50 kg (Canadian Sites only) ¹ Enrollment is defined as having signed consent to participate in the Limit-JIA study. The presence of any of the following will exclude a study participant from inclusion in the study: 1. Systemic JIA as defined by 2004 ILAR criteria1 Sacroiliitis (clinical or radiographic) Inflammatory bowel disease (IBD) History of psoriasis or currently active psoriasis History of uveitis or currently active uveitis Prior treatment with systemic medication(s) for JIA (e.g. one or more of the following: DMARD or biologic medication) Current or previous (within 30 days of enrollment) treatment with systemic glucocorticoids (A short course of oral prednisone [≤ 14 days] is allowed) History of active or chronic liver disease Chronic or acute renal disorder AST (SGOT), ALT (SGPT) or BUN >2 x ULN (upper limit of normal) or creatinine >1.5 mg/dL or any other laboratory abnormality considered by the examining physician to be clinically significant within 2 months of the enrollment visit Presence of any medical or psychological condition or laboratory result which would make the participant, in the opinion of the investigator, unsuitable for the study Participation in another concurrent clinical interventional study within 30 days of enrollment Known positive human immunodeficiency virus (HIV) Received a live virus vaccine within 1 month of the baseline visit Current or prior positive Purified Protein Derivative (PPD) test or Quantiferon Gold TB Pregnant, breast feeding, or planned breast feeding during the study duration Planned transfer to non-participating pediatric rheumatology center or adult rheumatologist in the next 12 months Active malignancy of any type or history of malignancy Chronic or active infection or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 30 days or oral antibiotics within 14 days prior to screening Primary language other than English or Spanish Positive for Hepatitis B surface antigen or core antibody <10 Kg in weight If a potential subject has symptoms consistent with COVID-19 and/or known COVID-19 exposure at screening, it is recommended that the site follow CDC guidance regarding testing and quarantine requirements. The subject can be re-screened when there is no longer concern for active infection. A subject with a positive COVID -19 test may be re-screened.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abatacept and Usual Care (Part I)<br>Weekly abatacept injection at standard dosing for weight plus usual care with steroid joint injection and non-steroidal anti-inflammatory drugs per the discretion of the treating provider | Drug: Abatacept Injection<br>* Supplied as a weekly injection via a pre-filled syringe<br>* Other names: Orencia;Other: Usual Care<br>* Usual care will be defined by the clinical management team but includes steroid joint injections and non- steroidal anti-inflammatory drugs<br>|
| Active Comparator: Active Comparator: Usual Care (Part I)<br>Usual care includes steroid joint injections and treatment with non-steroidal anti-inflammatory drugs at the discretion of the treating provider | Other: Usual Care<br>* Usual care will be defined by the clinical management team but includes steroid joint injections and non- steroidal anti-inflammatory drugs<br>|
| Experimental: Abatacept and Usual Care (Part II)<br>Weekly abatacept injection at standard dosing for weight plus usual care with steroid joint injection and non-steroidal anti-inflammatory drugs per the discretion of the treating provider | Drug: Abatacept Injection<br>* Supplied as a weekly injection via a pre-filled syringe<br>* Other names: Orencia;Other: Usual Care<br>* Usual care will be defined by the clinical management team but includes steroid joint injections and non- steroidal anti-inflammatory drugs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Joint Count by Physician Exam (Part I) | The number of affected joints involved at protocol specified visits by physician exam. | Baseline, up to 18 months | 
| Change in Joint Count by Physician Exam (Part II) | The number of affected joints involved at protocol specified visits by physician exam. | Baseline, up to 12 months | 
| Change in Number of participants with active anterior uveitis (Part I) | The presence of active anterior uveitis, defined according to the Standardization of Uveitis Nomenclature for Reporting Clinical Data (SUN criteria) as the presence of one or more cells in each 1mm x 1mm slit beam field,84 will be assessed at standard of care ophthalmology visits | Baseline, up to 18 months | 
| Change in Number of participants with active anterior uveitis (Part II) | The presence of active anterior uveitis, defined according to the Standardization of Uveitis Nomenclature for Reporting Clinical Data (SUN criteria) as the presence of one or more cells in each 1mm x 1mm slit beam field,84 will be assessed at standard of care ophthalmology visits | Baseline, up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain score as measured by PROMIS (patient reported outcome measurement system) (Part I) | We will use The Patient Reported Outcomes Measurement Information System (PROMIS), to compare patient and caregiver reported outcomes between the groups. PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centeredmeasures that evaluates and monitors physical, mental, and social health in adults and children. | Baseline, up to 18 months | 
| Change in pain score as measured by PROMIS (patient reported outcome measurement system) (Part II) | We will use The Patient Reported Outcomes Measurement Information System (PROMIS), to compare patient and caregiver reported outcomes between the groups. PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centeredmeasures that evaluates and monitors physical, mental, and social health in adults and children. | Baseline, up to 12 months | 
| Change in fatigue level as measured by PROMIS (Part I) | We will use The Patient Reported Outcomes Measurement Information System (PROMIS), to compare patient and caregiver reported outcomes between the groups. PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centeredmeasures that evaluates and monitors physical, mental, and social health in adults and children. | Baseline, up to 18 months | 
| Change in fatigue level as measured by PROMIS (Part II) | We will use The Patient Reported Outcomes Measurement Information System (PROMIS), to compare patient and caregiver reported outcomes between the groups. PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centeredmeasures that evaluates and monitors physical, mental, and social health in adults and children. | Baseline, up to 12 months | 
| Change in functional ability by PROMIS (Part I) | We will use The Patient Reported Outcomes Measurement Information System (PROMIS), to compare patient and caregiver reported outcomes between the groups. PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centeredmeasures that evaluates and monitors physical, mental, and social health in adults and children. | Baseline, up to 18 months | 
| Change in functional ability by PROMIS (Part II) | We will use The Patient Reported Outcomes Measurement Information System (PROMIS), to compare patient and caregiver reported outcomes between the groups. PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centeredmeasures that evaluates and monitors physical, mental, and social health in adults and children. | Baseline, up to 12 months | 
| Change in anxiety by PROMIS (Part I) | We will use The Patient Reported Outcomes Measurement Information System (PROMIS), to compare patient and caregiver reported outcomes between the groups. PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centeredmeasures that evaluates and monitors physical, mental, and social health in adults and children. | Baseline, up to 18 months | 
| Change in anxiety by PROMIS (Part II) | We will use The Patient Reported Outcomes Measurement Information System (PROMIS), to compare patient and caregiver reported outcomes between the groups. PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centeredmeasures that evaluates and monitors physical, mental, and social health in adults and children. | Baseline, up to 12 months | 
| Change in depression by PROMIS (Part I) | We will use The Patient Reported Outcomes Measurement Information System (PROMIS), to compare patient and caregiver reported outcomes between the groups. PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centeredmeasures that evaluates and monitors physical, mental, and social health in adults and children. | Baseline, up to 18 months | 
| Change in depression by PROMIS (Part II) | We will use The Patient Reported Outcomes Measurement Information System (PROMIS), to compare patient and caregiver reported outcomes between the groups. PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centeredmeasures that evaluates and monitors physical, mental, and social health in adults and children. | Baseline, up to 12 months | 
| Change in global health by PROMIS (Part I) | Global health is defined as overall well being; We will use The Patient Reported Outcomes Measurement Information System (PROMIS), to compare patient and caregiver reported outcomes between the groups. PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centeredmeasures that evaluates and monitors physical, mental, and social health in adults and children. | Baseline, up to 18 months | 
| Change in global health by PROMIS (Part II) | Global health is defined as overall well being; We will use The Patient Reported Outcomes Measurement Information System (PROMIS), to compare patient and caregiver reported outcomes between the groups. PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centeredmeasures that evaluates and monitors physical, mental, and social health in adults and children. | Baseline, up to 12 months | 
| Change in family impact by PedsQL (Part I) | The PedsQL (Pediatric Quality of Life InventoryTM) Measurement Model is a modular approach to measuring health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. | Baseline, up to 18 months | 
| Change in family impact by PedsQL (Part II) | The PedsQL (Pediatric Quality of Life InventoryTM) Measurement Model is a modular approach to measuring health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. | Baseline, up to 12 months | 
| Change in medications side effects by JAMAR (Part 1) |  | Baseline, up to 18 months | 
| Change in medications side effects by JAMAR (Part II) |  | Baseline, up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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uveitis, Polyarthritis, abatacept, prevention