Juvenile Idiopathic Arthritis
Conditions
Keywords
Polyarthritis, abatacept, uveitis, prevention
Brief summary
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
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 was discontinued. Part I participants continued 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 CARRA Registry patients who would have met major eligibility criteria for LIMIT-JIA.
Interventions
Supplied as a weekly injection via a pre-filled syringe
OTHERUsual Care
Usual care will be defined by the clinical management team but includes steroid joint injections and non- steroidal anti-inflammatory drugs
Sponsors
Duke University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
To be eligible for this trial, participants must meet all of the following criteria in order to be include in the study: 1. Age ≥ 2 years old and ≤16.5 years old 2. Clinical diagnosis of JIA by a pediatric rheumatologist within the past 6 months 3. Arthritis affecting ≤4 joints between disease onset and enrollment 4. Enrollment in the CARRA Registry 5. 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. 6. 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. 1\. Systemic JIA as defined by 2004 ILAR criteria1 2. Sacroiliitis (clinical or radiographic) 3. Inflammatory bowel disease (IBD) 4. History of psoriasis or currently active psoriasis 5. History of uveitis or currently active uveitis 6. Prior treatment with systemic medication(s) for JIA (e.g. one or more of the following: DMARD or biologic medication) 7. Current or previous (within 30 days of enrollment) treatment with systemic glucocorticoids (A short course of oral prednisone \[≤ 14 days\] is allowed) 8. History of active or chronic liver disease 9. Chronic or acute renal disorder 10. 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 11. 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 12. Participation in another concurrent clinical interventional study within 30 days of enrollment 13. Known positive human immunodeficiency virus (HIV) 14. Received a live virus vaccine within 1 month of the baseline visit 15. Current or prior positive Purified Protein Derivative (PPD) test or Quantiferon Gold TB 16. Pregnant, breast feeding, or planned breast feeding during the study duration 17. Planned transfer to non-participating pediatric rheumatology center or adult rheumatologist in the next 12 months 18. Active malignancy of any type or history of malignancy 19. 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 20. Primary language other than English or Spanish 21. Positive for Hepatitis B surface antigen or core antibody 22. \<10 Kg in weight 23. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of All Primary Endpoints | From randomization to day 410 | Any of the following from randomization to day 410: polyarthritis \[\>=5 cumulative active joint count\], uveitis, initiation of systemic glucocorticoids (IV or PO), DMARDs or biologics. |
| Number of Participants With Polyarthritis | From randomization to day 592 | Polyarthritis is defined as \>=5 cumulative active joint count. |
| Number of Participants With Uveitis | From randomization to day 410 | — |
| Number of Participants With Systemic Medications | From randomization day 410 | Systemic glucocorticoids, Disease-Modifying Antirheumatic Drugs (DMARDs) or biologics. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Inactive Disease or Remission | From baseline up to 12 months | Clinical Inactive disease at any visit is a composite outcome consisting of all of: No active joints (Current Active Joint Count=0), No uveitis (Uveitis=No or not reported), Normal ESR (if obtained) (N/D or ESR≤ ULN or unrelated to JIA if \>ULN), Normal CRP (if obtained) (N/D or CRP≤ ULN or unrelated to JIA if \>ULN), AM stiffness duration=None or ≤ 15 minutes, Physician Global score=0. |
| Number of Participants With Disease Extension | From baseline up to 12 months | Disease extension defined as development of polyarthritis or uveitis. |
| Number of New Active Joints Per Participant | From baseline up to 12 months | Total number of joints that were not active prior to or at baseline, and became active after randomization. |
| Number of Intra-articular Glucocorticoid Joint Injections Per Participant | From baseline up to 12 months | Intra-articular glucocorticoid joint injections are reported in the CARRA Registry CRF at each Limit-JIA or CARRA Registry visit. |
| PROMIS (Patient-Reported Outcomes Measurement Information System) Pediatric Pain Interference | 6 months and 12 months | PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. PROMIS scores are T-scores and have a mean of 50 and standard deviation of 10. |
| PROMIS (Patient-Reported Outcomes Measurement Information System) Pediatric Fatigue | 6 months and 12 months | PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. PROMIS scores are T-scores and have a mean of 50 and standard deviation of 10. |
| PROMIS (Patient-Reported Outcomes Measurement Information System) Upper Extremity Function | 6 months and 12 months | PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. PROMIS scores are T-scores and have a mean of 50 and standard deviation of 10. |
| PROMIS (Patient-Reported Outcomes Measurement Information System) Mobility | 6 months and 12 months | PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. PROMIS scores are T-scores and have a mean of 50 and standard deviation of 10. |
| PROMIS (Patient-Reported Outcomes Measurement Information System) Anxiety | 6 months | PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. PROMIS scores are T-scores and have a mean of 50 and standard deviation of 10. |
| PROMIS (Patient-Reported Outcomes Measurement Information System) Depression | 6 months | PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. PROMIS scores are T-scores and have a mean of 50 and standard deviation of 10. |
| PROMIS (Patient-Reported Outcomes Measurement Information System) Global Health | 6 months and 12 months | PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. PROMIS scores are T-scores and have a mean of 50 and standard deviation of 10. |
| Juvenile Arthritis Disease Activity Score (JADAS) | 6 months and 12 months | The JADAS (Juvenile Arthritis Disease Activity Score) is a composite tool used to assess disease activity in children with Juvenile Idiopathic Arthritis (JIA). The total score ranges from 0 to 40, where a higher score indicates a more severe level of disease activity. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORLaura Schanberg, MD
Duke University
PRINCIPAL_INVESTIGATOREveline Wu, MD
University of North Carolina, Chapel Hill
Participant flow
Pre-assignment details
Usual Care (Part II) participants were historical controls used for analysis and not considered enrolled.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 6.10 years STANDARD_DEVIATION 4.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 87 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 694 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 18 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 72 Participants |
| Race (NIH/OMB) White | 569 Participants |
| Region of Enrollment United States | 81 Participants |
| Sex: Female, Male Female | 516 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 80 | 0 / 662 |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 80 | 0 / 662 |
| serious Total, serious adverse events | 1 / 20 | 0 / 20 | 3 / 80 | 0 / 662 |
Outcome results
None listed