Trial of Early Aggressive Drug Therapy in Juvenile Idiopathic Arthritis

• ClinicalTrials.gov Identifier: NCT00443430
• Recruitment Status: Completed
• First Posted: March 6, 2007
• Results First Posted: May 31, 2013
• Last Update Posted: May 31, 2013
• Sponsor: Seattle Children's Hospital
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Amgen
• Information provided by (Responsible Party): Carol Wallace, Seattle Children's Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Juvenile Chronic Polyarthritis; Juvenile Idiopathic Arthritis; Juvenile Rheumatoid Arthritis	Drug: methotrexate; Drug: methotrexate - etanercept - prednisolone arm	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 85 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Trial of Early Aggressive Therapy in Juvenile Idiopathic Arthritis (TREAT in JIA)
• Study Start Date: May 2007
• Actual Primary Completion Date: October 2010
• Actual Study Completion Date: October 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Proportion of Participants Who Attain Inactive Disease by 6 Months [ Time Frame: 6 months after initiation of study intervention ]

Secondary Outcome Measures :

1. 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 ]
2. Clinical Remission on Medication [ Time Frame: 12 months or end of study ]
   6 months of clinical inactive disease

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Stanford University Medical Center

Palo Alto, California, United States, 94305

Rady Children's Hospital

San Diego, California, United States, 92123-4282

University of California San Francisco Medical Center

San Francisco, California, United States, 94143

United States, Massachusetts

Children's Hospital of Boston

Boston, Massachusetts, United States, 02115

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New York

Children's Hospital at Montefiore

Bronx, New York, United States, 10467

Schneider Children's Hospital

New Hyde Park, New York, United States, 11040

United States, North Carolina

Duke University

Durham, North Carolina, United States, 27710

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229-3039

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

Children's Hospital of Columbus

Columbus, Ohio, United States, 43205

United States, Oklahoma

Oklahoma University Health Science Center

Oklahoma City, Oklahoma, United States, 73104

United States, Texas

Texas Scottish Rite Hospital

Dallas, Texas, United States, 75219

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84132

United States, Washington

Seattle Children's Hospital and Regional Medical Center

Seattle, Washington, United States, 98105

Sponsors and Collaborators

Seattle Children's Hospital

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

Amgen

Investigators

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

More Information

Additional Information:

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

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. doi: 10.1002/art.21885.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

• Responsible Party: Carol Wallace, Principal Investigator, Seattle Children's Hospital
• ClinicalTrials.gov Identifier: NCT00443430
• Other Study ID Numbers: R01AR049762 ( U.S. NIH Grant/Contract ); 5R01AR049762-02 ( U.S. NIH Grant/Contract )
• First Posted: March 6, 2007
• Results First Posted: May 31, 2013
• Last Update Posted: May 31, 2013
• Last Verified: May 2013

Keywords provided by Carol Wallace, Seattle Children's Hospital:

Childhood Arthritis; Juvenile Arthritis; Juvenile Arthritis Treatment; Childhood Arthritis Drug Treatment; Juvenile Arthritis Remission; Inactive Disease in Juvenile Arthritis; Childhood Polyarthritis; Extended Oligoarthritis

Additional relevant MeSH terms:

Arthritis; Arthritis, Juvenile; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Prednisone; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Etanercept; Methotrexate; Prednisolone hemisuccinate; Prednisolone phosphate; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Antimetabolites, Antineoplastic; Antimetabolites