Trial of Early Aggressive Drug Therapy in Juvenile Idiopathic Arthritis

Condition(s) targeted: Polyarticular Juvenile Idiopathic Arthritis; Juvenile Idiopathic Arthritis; Juvenile Rheumatoid Arthritis; Extended Oligoarthritis Juvenile Idiopathic Arthritis

Intervention: methotrexate (Drug); methotrexate, etanercept, prednisolone (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Official(s) and/or principal investigator(s):
Carol A. Wallace, MD, Principal Investigator, Affiliation: Childrens Hospital and Regional Medical Center

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

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

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

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

Primary outcome: Proportion of participants who attain inactive disease by 6 months

Secondary outcome: Safety profiles, including the number of treatment-emergent, serious, or unexpected adverse events and other important medical events

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.

Minimum age: 2 Years. Maximum age: 17 Years. Gender(s): Both.

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 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

- 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

Carol A. Wallace, MD, Phone: 206-987-2057, Email: carrainfo@stanford.edu

University of California San Francisco Medical Center, San Francisco, California 94143, United States; Recruiting
Diana Milojevic, MD, Phone: 415-502-4940, Email: carrainfo@stanford.edu
Diana Milojevic, MD, Principal Investigator

Rady Children's Hospital, San Diego, California 92123-4282, United States; Recruiting
Ilona Szer, MD, Email: carrainfo@stanford.edu
Ilona Szer, MD, Principal Investigator

Stanford University Medical Center, Palo Alto, California, United States; Recruiting
Peter Chiraseveenuprapund, Email: carrainfo@standford.edu
Abirami Sivagnanasundaram, Email: carrainfo@standford.edu
Peter Chiraseveenuprapund, MD, Principal Investigator

James Whitcomb Riley Hospital for Children, Indianapolis, Indiana 46202, United States; Recruiting
Andrea Bamford, Phone: 317-278-0266, Email: abamford@iupui.edu
Suzanne Bowyer, MD, Principal Investigator

Children's Hospital of Boston, Boston, Massachusetts 02115, United States; Recruiting
Robert Sundel, MD, Email: carrainfo@stanford.edu
Robert Sundel, MD, Principal Investigator

Hackensack University Medical Center, Hackensack, New Jersey 07601, United States; Recruiting
Yukiko Kimura, MD, Phone: 201-996-5306, Email: carrainfo@stanford.edu
Yuki Kimura, MD, Principal Investigator

Schneider Children's Hospital, New Hyde Park, New York 11040, United States; Recruiting
Beth Gottlieb, MD, Email: carrainfo@stanford.edu
Beth Gottlieb, MD, Principal Investigator

Children's Hospital at Montefiore, Bronx, New York 10467, United States; Recruiting
Norm Ilowite, MD, Phone: 718-741-2456, Email: nilowite@montefiore.org
Norm Ilowite, MD, Principal Investigator

Duke University, Durham, North Carolina 27710, United States; Recruiting
Laura Schanberg, MD, Email: carrainfo@stanford.edu
Laura Schanberg, MD, Principal Investigator

Children's Hospital of Columbus, Columbus, Ohio 43205, United States; Recruiting
Gloria Higgins, PhD, MD, Phone: 614-722-5525, Email: carrainfo@stanford.edu
Gloria Higgins, Principal Investigator

Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States; Recruiting
Sonya Crook, RN, Email: crooks@ccf.org
Phil Hashkes, MD, Principal Investigator

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States; Recruiting
Daniel J. Lovell, MD, MPH, Phone: 513-636-8071, Email: carrainfo@stanford.edu
Hermine Brunner, MD, Email: carrainfo@stanford.edu
Hermine Brunner, MD, Principal Investigator

Oklahoma University Health Science Center, Oklahoma City, Oklahoma 73104, United States; Recruiting
Kathleen O'Neil, MD, Email: carrainfo@stanford.edu
Kathleen O'Neil, MD, Principal Investigator

Childrens Hospital Pittsburg, Pittsburg, Pennsylvania, United States; Not yet recruiting
Margalit Rosenkranz, Email: carrainfo@stanford.edu
Judy Henry, Email: carrainfo@stanford.edu
Margalit Rosenkranz, Principal Investigator

Texas Scottish Rite Hospital, Dallas, Texas 75219, United States; Recruiting
Heather Benham, RN, CPNP, Email: Heather.Benham@tsrh.org
Lynn Punaro, MD, Principal Investigator

University of Utah, Salt Lake City, Utah 84132, United States; Recruiting
Andrew Zeft, MD, Email: carrainfo@stanford.edu
Andrew Zeft, MD, Principal Investigator

Seattle Children's Hospital and Regional Medical Center, Seattle, Washington 98105, United States; Recruiting
Jennifer Wargula, MD, Phone: 206-884-4558, Email: carrainfo@stanford.edu
Stephanie Hamilton, BA, BSN, Phone: 206-987-4558, Email: stephanie.hamilton@seattlechildrens.org
Jennifer Wargula, MD, Principal Investigator

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

Related publications:

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.

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

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.

Starting date: May 2007
Ending date: December 2009
Last updated: September 3, 2008