Clinical trial NCT00443430: Trial of Early Aggressive Drug Therapy in Juvenile Idiopathic Arthritis
Official title: Trial of Early Aggressive Therapy in Juvenile Idiopathic Arthritis (TREAT in JIA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Juvenile Chronic Polyarthritis
Juvenile Idiopathic Arthritis
Juvenile Rheumatoid Arthritis
Keywords: Childhood Arthritis
Juvenile Arthritis
Juvenile Arthritis Treatment
Childhood Arthritis Drug Treatment
Juvenile Arthritis Remission
Inactive Disease in Juvenile Arthritis
Childhood Polyarthritis
Extended Oligoarthritis
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
name: Amgen
First posted: 2007-03-06
Enrollment: 85
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare two aggressive drug regimens for children with poly-juvenile idiopathic arthritis (JIA) and extended oligo JIA.

Detailed description: JIA is a type of arthritis with no definite cause and an onset prior to 16 years of age. JIA causes joint destruction, pain, and permanent disability. There are multiple types of JIA; collectively, they represent one of the most common chronic diseases in children and the most prevalent pediatric rheumatic illness. Poly-JIA, one type of JIA, affects at least five joints in the body within the first 6 months of disease. Long-term remission of poly-JIA is uncommon, and most children must remain on multiple combinations of medications for many years. The usual treatment for poly-JIA is based upon the gradual addition of medications that might be more effective in treating this disease. There is a need to find uniformly effective treatments for children with poly-JIA. Based on previous adult arthritis studies, there appears to be an early window of opportunity in the disease progression during which aggressive therapy has a profound beneficial long-term effect. The purpose of this study is to compare the effectiveness of two aggressive drug regimens in treating children with poly-JIA. Specifically, the study will determine whether aggressive therapy started in the first 6 months of disease onset can result in inactive disease and clinical remission while on these medications.

All participants will receive weekly methotrexate shots while in the study. In addition, participants will be randomly assigned to one of two groups:

* Group 1 participants will receive placebo etanercept shots for up to 12 months and daily placebo prednisolone liquid for 4 months.
* Group 2 participants will receive etanercept shots for up to 12 months and daily prednisolone liquid for 4 months.

The study will last up to 12 months and include two parts. Part A will last 1 to 6 months, depending on response to assigned treatments. If participants are still experiencing active arthritis at 6 months, they will be offered open-label treatment with etanercept and prednisolone. If participants experience inactive disease any time prior to 6 months, they will enter Part B of the study. During Part B, which will last up to 6 months, participants will remain on the same treatment regimen that they were provided in Part A. If participants experience inactive disease followed by a flare of disease any time during the study, they will stop participating.

During the study, there will be 11 study visits for all participants. Study visits will include a physical exam, including joint evaluations; blood and urine collection; and questionnaires regarding function, quality of life, medication compliance, other medications used, infections, and adverse symptoms.

Blood will be collected for translational studies.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of active poly-JIA as determined by International League of Associations for Rheumatology (ILAR) criteria
* Onset of signs and symptoms of poly-JIA for 12 months or less prior to study screening
* Willing to use acceptable forms of contraception for the duration of the study and for 3 months after the study
* Parent or guardian willing to provide informed consent
* Able to attend all study visits

Exclusion Criteria:

* Received or currently receiving disease-modifying antirheumatic drugs (DMARDs), biologic, or prednisone for any duration for treatment of poly-JIA, with the following exceptions:

  1. Methotrexate duration must be less than or equal to 6 weeks at a dose of less than or equal to 0.5 mg/kg/week (40 mg max),
  2. Steroid use has been less than or equal to 4 weeks and the subject is off of steroids for at least 1 week prior to enrollment
* Received intramuscular or soft-tissue injections of corticosteroids for treatment of poly-JIA before receiving the first dose of study medication. Up to 2 joint injections with intra-articular steroids (IAS) will be allowed up to 7 days after the baseline visit.
* History of or active cancer of any type
* Active gastrointestinal disease (e.g., inflammatory bowel disease)
* Chronic or acute kidney or liver disorder
* Significant blood clotting defect
* AST (SGOT), ALT (SGPT), or BUN levels more than two times the upper level of normal, creatinine levels more than 1.5 mg/dl, or any other laboratory abnormality considered to be clinically significant within 28 days prior to baseline
* Chronic condition (e.g., diabetes, epilepsy) that is either not stable or poorly controlled and may interfere with study participation
* Received any investigational medication within 30 days prior to the first dose of study medication or scheduled to receive an investigational drug (other than the study medications) during the course of the study
* Chronic or active infection or any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 30 days prior to study screening
* HIV infected
* Known past or current hepatitis infection
* Received a live virus vaccine within 1 month prior to baseline
* Purified protein derivative (PPD) positive (positive tuberculosis \[TB\] test)
* Pregnancy
* Any medical condition that would make study participation difficult or inadvisable in the opinion of the investigator
* History of or current psychiatric illness that would interfere with study participation
* History of alcohol or drug abuse within the 6 months prior to study entry that would interfere with study participation
* Inability to comply with study requirements for any reason

Primary outcomes:
measure: Proportion of Participants Who Attain Inactive Disease by 6 Months
timeFrame: 6 months after initiation of study intervention
Secondary outcomes:
measure: Safety Profiles, Including the Number of Treatment-emergent, Serious, or Unexpected Adverse Events and Other Important Medical Events
timeFrame: Over 12 months maximum study participation per subject
measure: Clinical Remission on Medication
timeFrame: 12 months or end of study
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Boston
country: United States
facility: Children's Hospital of Boston
state: Massachusetts
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Children's Hospital at Montefiore
state: New York
city: New Hyde Park
country: United States
facility: Schneider Children's Hospital
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Children's Hospital of Columbus
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Health Science Center
state: Oklahoma
city: Dallas
country: United States
facility: Texas Scottish Rite Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital and Regional Medical Center
state: Washington
Study officials:
affiliation: Childrens Hospital and Regional Medical Center
name: Carol A. Wallace, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lovell DJ, Reiff A, Jones OY, Schneider R, Nocton J, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Whitmore JB, White B, Giannini EH; Pediatric Rheumatology Collaborative Study Group. Long-term safety and efficacy of etanercept in children with polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum. 2006 Jun;54(6):1987-94. doi: 10.1002/art.21885.
citation: Wallace CA. Current management of juvenile idiopathic arthritis. Best Pract Res Clin Rheumatol. 2006 Apr;20(2):279-300. doi: 10.1016/j.berh.2005.11.008.
citation: Wallace CA, Ruperto N, Giannini E; Childhood Arthritis and Rheumatology Research Alliance; Pediatric Rheumatology International Trials Organization; Pediatric Rheumatology Collaborative Study Group. Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol. 2004 Nov;31(11):2290-4.
citation: Jiang K, Wong L, Sawle AD, Frank MB, Chen Y, Wallace CA, Jarvis JN. Whole blood expression profiling from the TREAT trial: insights for the pathogenesis of polyarticular juvenile idiopathic arthritis. Arthritis Res Ther. 2016 Jul 7;18(1):157. doi: 10.1186/s13075-016-1059-1.
citation: Wallace CA, Giannini EH, Spalding SJ, Hashkes PJ, O'Neil KM, Zeft AS, Szer IS, Ringold S, Brunner HI, Schanberg LE, Sundel RP, Milojevic DS, Punaro MG, Chira P, Gottlieb BS, Higgins GC, Ilowite NT, Kimura Y, Johnson A, Huang B, Lovell DJ; Childhood Arthritis and Rheumatology Research Alliance (CARRA). Clinically inactive disease in a cohort of children with new-onset polyarticular juvenile idiopathic arthritis treated with early aggressive therapy: time to achievement, total duration, and predictors. J Rheumatol. 2014 Jun;41(6):1163-70. doi: 10.3899/jrheum.131503. Epub 2014 May 1.
citation: Wallace CA, Giannini EH, Spalding SJ, Hashkes PJ, O'Neil KM, Zeft AS, Szer IS, Ringold S, Brunner HI, Schanberg LE, Sundel RP, Milojevic D, Punaro MG, Chira P, Gottlieb BS, Higgins GC, Ilowite NT, Kimura Y, Hamilton S, Johnson A, Huang B, Lovell DJ; Childhood Arthritis and Rheumatology Research Alliance. Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis. Arthritis Rheum. 2012 Jun;64(6):2012-21. doi: 10.1002/art.34343. Epub 2011 Dec 19.