Official Title: “Trial of Early Aggressive Therapy in Juvenile Idiopathic Arthritis (TREAT in JIA)”

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

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2009

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.

Intervention(s) in this Clinical Trial

• Drug: methotrexate
  • Methotrexate 0.5 mg/kg given by sub cutaneous injection once per week, plus placebo etanercept and and placebo prednisolone
• Drug: methotrexate, etanercept, prednisolone
  • methotrexate 0.5 mg/kg given by sub cutaneous injection once per week, plus etanercept 0.8 mg/kg given by sub cutaneous injection once per week, plus prednisolone, by mouth daily with decreasing dose tapered over 16 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Methotrexate 0.5 mg/kg given by subcutaneous injection once per week, plus placebo etanercept and placebo prednisolone
• Experimental: 2
  • Methotrexate 0.5 mg/kg given by subcutaneous injection once per week, plus etanercept 0.8 mg/kg given by subcutaneous injection once per week, plus prednisolone by mouth daily with decreasing dose tapered over 16 weeks

Primary Measures

• Proportion of participants who attain inactive disease by 6 months
  • Time Frame: 6 months after initiation of study intervention
    Safety Issue?: No

Secondary Measures

• Safety profiles, including the number of treatment-emergent, serious, or unexpected adverse events and other important medical events
  • Time Frame: Over 12 months maximum study participation per subject
    Safety Issue?: Yes

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 6 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 biologic disease-modifying antirheumatic drugs (DMARDs) 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, intra-articular, 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 2 weeks 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 or oral antibiotics within 14 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 4 Years

Maximum Age for this Clinical Trial: 16 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Overall Clinical Trial Officials and Contacts

Carol A. Wallace, MD Principal Investigator Childrens Hospital and Regional Medical Center  

Overall Contact: Carol A. Wallace, MD 206-987-2057 carrainfo@stanford.edu

Information obtained from ClinicalTrials.gov on August 08, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00443430

Study ID Number: R01 AR049762

ClinicalTrials.gov Identifier: NCT00443430

Health Authority: United States: Federal Government

Click here for the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Web site