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

• Sponsor: Duke University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03841357
• Collaborator: (none)
• Enrollment: 130
• Locations: 26
• Arms: 3
• Anticipated Duration (Months): 49.5
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Juvenile Idiopathic Arthritis	Drug: Abatacept Injection; Other: Usual Care	Phase 3

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 130 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Oct 29, 2019
• Anticipated Primary Completion Date: Dec 15, 2023
• Anticipated Study Completion Date: Dec 15, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Joint Count by Physician Exam (Part I) [Baseline, up to 18 months]

   The number of affected joints involved at protocol specified visits by physician exam.

2. Change in Joint Count by Physician Exam (Part II) [Baseline, up to 12 months]

   The number of affected joints involved at protocol specified visits by physician exam.

3. Change in Number of participants with active anterior uveitis (Part I) [Baseline, up to 18 months]

   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

4. Change in Number of participants with active anterior uveitis (Part II) [Baseline, up to 12 months]

   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

Secondary Outcome Measures

1. Change in pain score as measured by PROMIS (patient reported outcome measurement system) (Part I) [Baseline, up to 18 months]

   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.

2. Change in pain score as measured by PROMIS (patient reported outcome measurement system) (Part II) [Baseline, up to 12 months]

   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.

3. Change in fatigue level as measured by PROMIS (Part I) [Baseline, up to 18 months]

   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.

4. Change in fatigue level as measured by PROMIS (Part II) [Baseline, up to 12 months]

   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.

5. Change in functional ability by PROMIS (Part I) [Baseline, up to 18 months]

   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.

6. Change in functional ability by PROMIS (Part II) [Baseline, up to 12 months]

   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.

7. Change in anxiety by PROMIS (Part I) [Baseline, up to 18 months]

   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.

8. Change in anxiety by PROMIS (Part II) [Baseline, up to 12 months]

   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.

9. Change in depression by PROMIS (Part I) [Baseline, up to 18 months]

   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.

10. Change in depression by PROMIS (Part II) [Baseline, up to 12 months]

    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.

11. Change in global health by PROMIS (Part I) [Baseline, up to 18 months]

    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.

12. Change in global health by PROMIS (Part II) [Baseline, up to 12 months]

    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.

13. Change in family impact by PedsQL (Part I) [Baseline, up to 18 months]

    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.

14. Change in family impact by PedsQL (Part II) [Baseline, up to 12 months]

    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.

15. Change in medications side effects by JAMAR (Part 1) [Baseline, up to 18 months]

16. Change in medications side effects by JAMAR (Part II) [Baseline, up to 12 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 16 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	University of California at San Francisco Medical Center	San Francisco	California	United States	94143
3	The Children's Hospital Colorado	Aurora	Colorado	United States	80045
4	Shands at the University of Florida	Gainesville	Florida	United States	32610
5	Childrens Memorial Hospital/ Ann and Robert Lurie Children's Hospital	Chicago	Illinois	United States	60611
6	University of Chicago	Chicago	Illinois	United States	60637
7	Riley Hospital for Children at Indiana University Health	Indianapolis	Indiana	United States	46202
8	University of Iowa Hospitals of Clinics	Iowa City	Iowa	United States	52242
9	University of Louisville School of Medicine/ Norton Charities Pediatric Clinical Research Unit	Louisville	Kentucky	United States	40202
10	Boston Children's Hospital	Boston	Massachusetts	United States	02115
11	University of Minnesota; Children's Hospital and Clinics of Minnesota	Minneapolis	Minnesota	United States	55454
12	Mayo Clinic	Rochester	Minnesota	United States	55905
13	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
14	The Pediatric Specialty Center at Saint Barnabas/RWJ Barnabas Health	West Orange	New Jersey	United States	07052
15	Children's Hospital at Montefiore/ Albert Einstein University Hospital	Bronx	New York	United States	10461
16	Hospital of Special Surgery	New York	New York	United States	10021
17	University of North Carolina	Chapel Hill	North Carolina	United States	27514
18	Levine Children's Hospital/ Carolina Medical Center	Charlotte	North Carolina	United States	28203
19	Duke Children's Hospital and Health Center	Durham	North Carolina	United States	27705
20	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
21	MetroHealth System	Cleveland	Ohio	United States	44109
22	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
23	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
24	Monroe Carell Jr Children's Hospital at Vanderbilt	Nashville	Tennessee	United States	37232
25	University of Utah	Salt Lake City	Utah	United States	84158
26	Seattle Children's Hospital	Seattle	Washington	United States	98105

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: Laura Schanberg, MD, Duke University
• Principal Investigator: Stephen Balevic, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03841357
• Other Study ID Numbers: Pro00100523
• First Posted: Feb 15, 2019
• Last Update Posted: Aug 18, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Duke University: Polyarthritis; abatacept; uveitis; prevention
• Additional relevant MeSH terms: Arthritis; Arthritis, Juvenile; Abatacept

Study Results

No Results Posted as of Aug 18, 2022