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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Juvenile Idiopathic Arthritis
• Intervention / Treatment: Drug: Abatacept Injection; Other: Usual Care

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.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Alex Fist, MPH; Phone Number: 919-660-8136; Email: alex.fist@duke.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California at San Francisco Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • The Children's Hospital Colorado
  • Florida
    • Gainesville, Florida, United States, 32610
      • Shands at the University of Florida
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children at Indiana University Health
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals of Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville School of Medicine/ Norton Charities Pediatric Clinical Research Unit
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota; Children's Hospital and Clinics of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Bronx, New York, United States, 10461
      • Children's Hospital at Montefiore/ Albert Einstein University Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44109
      • MetroHealth System
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Monroe Carell Jr Children's Hospital at Vanderbilt
  • Utah
    • Salt Lake City, Utah, United States, 84158
      • University of Utah
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abatacept and Usual Care (Part I); 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; Supplied as a weekly injection via a pre-filled syringe; Other Names: Orencia; Other: Usual Care; Usual care will be defined by the clinical management team but includes steroid joint injections and non- steroidal anti-inflammatory drugs
Active Comparator: Active Comparator: Usual Care (Part I); Usual care includes steroid joint injections and treatment with non-steroidal anti-inflammatory drugs at the discretion of the treating provider	Other: Usual Care; Usual care will be defined by the clinical management team but includes steroid joint injections and non- steroidal anti-inflammatory drugs
Experimental: Abatacept and Usual Care (Part II); 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; Supplied as a weekly injection via a pre-filled syringe; Other Names: Orencia; Other: Usual Care; Usual care will be defined by the clinical management team but includes steroid joint injections and non- steroidal anti-inflammatory drugs

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Laura Schanberg, MD, Duke University; Principal Investigator: Eveline Wu, MD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2019
• Primary Completion (Estimated): January 15, 2025
• Study Completion (Estimated): January 15, 2025

Study Registration Dates

• First Submitted: January 30, 2019
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: prevention; abatacept; uveitis; Polyarthritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Juvenile; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: Pro00100523

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No