Trial of Early Aggressive Drug Therapy in Juvenile Idiopathic Arthritis

Juvenile Idiopathic Arthritis Clinical Trial

Official title:

Trial of Early Aggressive Therapy in Juvenile Idiopathic Arthritis (TREAT in JIA)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00443430
• Other study ID #: R01AR049762
• Secondary ID: 5R01AR049762-02
• Status: Completed
• Phase: Phase 4
• First received: March 2, 2007
• Last updated: May 30, 2013
• Start date: May 2007
• Est. completion date: October 2010

Study information

• Verified date: May 2013
• Source: Seattle Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 17 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Arthritis, Rheumatoid
• Juvenile Chronic Polyarthritis
• Juvenile Idiopathic Arthritis
• Juvenile Rheumatoid Arthritis

Intervention

Drug:
• methotrexate
Methotrexate 0.5 mg/kg given by sub cutaneous injection once per week, plus placebo etanercept and and placebo prednisolone
• methotrexate - etanercept - prednisolone arm
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.

Locations

Country	Name	City	State
United States	Children's Hospital of Boston	Boston	Massachusetts
United States	Children's Hospital at Montefiore	Bronx	New York
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Children's Hospital of Columbus	Columbus	Ohio
United States	Texas Scottish Rite Hospital	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Schneider Children's Hospital	New Hyde Park	New York
United States	Oklahoma University Health Science Center	Oklahoma City	Oklahoma
United States	Stanford University Medical Center	Palo Alto	California
United States	University of Utah	Salt Lake City	Utah
United States	Rady Children's Hospital	San Diego	California
United States	University of California San Francisco Medical Center	San Francisco	California
United States	Seattle Children's Hospital and Regional Medical Center	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Seattle Children's Hospital	Amgen, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View Citation

Wallace CA. Current management of juvenile idiopathic arthritis. Best Pract Res Clin Rheumatol. 2006 Apr;20(2):279-300. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants Who Attain Inactive Disease by 6 Months		6 months after initiation of study intervention	No
Secondary	Safety Profiles, Including the Number of Treatment-emergent, Serious, or Unexpected Adverse Events and Other Important Medical Events		Over 12 months maximum study participation per subject	Yes
Secondary	Clinical Remission on Medication	6 months of clinical inactive disease	12 months or end of study	No

External Links

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