Clinical trial NCT03841357: Preventing Extension of Oligoarticular Juvenile Idiopathic Arthritis JIA (Limit-JIA)
Official title: An Open Label, Multi-Center, Phase 3 Efficacy Study of Sub-Q Abatacept in Preventing Extension of Oligoarticular Juvenile Idiopathic Arthritis JIA (Limit-JIA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Juvenile Idiopathic Arthritis
Keywords: Polyarthritis
abatacept
uveitis
prevention
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2019-02-15
Enrollment: 121
Sex: ALL
Minimum age (years): 2
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

Eligibility 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.

Primary outcomes:
measure: Change in Joint Count by Physician Exam (Part I)
timeFrame: Baseline, up to 18 months
measure: Change in Joint Count by Physician Exam (Part II)
timeFrame: Baseline, up to 12 months
measure: Change in Number of participants with active anterior uveitis (Part I)
timeFrame: Baseline, up to 18 months
measure: Change in Number of participants with active anterior uveitis (Part II)
timeFrame: Baseline, up to 12 months
Secondary outcomes:
measure: Change in pain score as measured by PROMIS (patient reported outcome measurement system) (Part I)
timeFrame: Baseline, up to 18 months
measure: Change in pain score as measured by PROMIS (patient reported outcome measurement system) (Part II)
timeFrame: Baseline, up to 12 months
measure: Change in fatigue level as measured by PROMIS (Part I)
timeFrame: Baseline, up to 18 months
measure: Change in fatigue level as measured by PROMIS (Part II)
timeFrame: Baseline, up to 12 months
measure: Change in functional ability by PROMIS (Part I)
timeFrame: Baseline, up to 18 months
measure: Change in functional ability by PROMIS (Part II)
timeFrame: Baseline, up to 12 months
measure: Change in anxiety by PROMIS (Part I)
timeFrame: Baseline, up to 18 months
measure: Change in anxiety by PROMIS (Part II)
timeFrame: Baseline, up to 12 months
measure: Change in depression by PROMIS (Part I)
timeFrame: Baseline, up to 18 months
measure: Change in depression by PROMIS (Part II)
timeFrame: Baseline, up to 12 months
measure: Change in global health by PROMIS (Part I)
timeFrame: Baseline, up to 18 months
measure: Change in global health by PROMIS (Part II)
timeFrame: Baseline, up to 12 months
measure: Change in family impact by PedsQL (Part I)
timeFrame: Baseline, up to 18 months
measure: Change in family impact by PedsQL (Part II)
timeFrame: Baseline, up to 12 months
measure: Change in medications side effects by JAMAR (Part 1)
timeFrame: Baseline, up to 18 months
measure: Change in medications side effects by JAMAR (Part II)
timeFrame: Baseline, up to 12 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California at San Francisco Medical Center
state: California
city: Aurora
country: United States
facility: The Children's Hospital Colorado
state: Colorado
city: Gainesville
country: United States
facility: Shands at the University of Florida
state: Florida
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals of Clinics
state: Iowa
city: Louisville
country: United States
facility: University of Louisville School of Medicine/ Norton Charities Pediatric Clinical Research Unit
state: Kentucky
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota; Children's Hospital and Clinics of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Children's Hospital at Montefiore/ Albert Einstein University Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth System
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Monroe Carell Jr Children's Hospital at Vanderbilt
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Duke University
name: Laura Schanberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Eveline Wu, MD
role: PRINCIPAL_INVESTIGATOR
References: