Trial of Early Aggressive Drug Therapy in Juvenile Idiopathic Arthritis

May 30, 2013 updated by: Carol Wallace, Seattle Children's Hospital

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) and extended oligo JIA.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

85

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94305
        • Stanford University Medical Center
      • San Diego, California, United States, 92123-4282
        • Rady Children's Hospital
      • San Francisco, California, United States, 94143
        • University Of California San Francisco Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital of Boston
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • Bronx, New York, United States, 10467
        • Children's Hospital at Montefiore
      • New Hyde Park, New York, United States, 11040
        • Schneider Children's Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Columbus, Ohio, United States, 43205
        • Children's Hospital of Columbus
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University Health Science Center
    • Texas
      • Dallas, Texas, United States, 75219
        • Texas Scottish Rite Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital and Regional Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Methotrexate Arm
Methotrexate 0.5 mg/kg given by subcutaneous injection once per week, plus placebo etanercept and placebo prednisolone
Drug: methotrexate
Methotrexate 0.5 mg/kg given by sub cutaneous injection once per week, plus placebo etanercept and and placebo prednisolone
Other Names:
  • placebo enbrel
  • placebo prednisolone
Active Comparator: Methotrexate-Etanercept-Prednisolone Arm
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
Drug: 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.
Other Names:
  • enbrel
  • prednisone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of Participants Who Attain Inactive Disease by 6 Months
Time Frame: 6 months after initiation of study intervention
6 months after initiation of study intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Over 12 months maximum study participation per subject
Clinical Remission on Medication
Time Frame: 12 months or end of study
6 months of clinical inactive disease
12 months or end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seattle Children's Hospital

Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Amgen

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (Actual)

October 1, 2010

Study Completion (Actual)

October 1, 2010

Study Registration Dates

First Submitted

March 2, 2007

First Submitted That Met QC Criteria

March 2, 2007

First Posted (Estimate)

March 6, 2007

Study Record Updates

Last Update Posted (Estimate)

May 31, 2013

Last Update Submitted That Met QC Criteria

May 30, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R01AR049762 (U.S. NIH Grant/Contract)
  • 5R01AR049762-02 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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