ENBREL(R) (Etanercept) Safety Study in Children With Juvenile Rheumatoid Arthritis

Condition(s) targeted: Juvenile Rheumatoid Arthritis

Intervention: ENBREL(R) (etanercept) (Drug)

Phase: Phase 4

Status: Active, not recruiting

Sponsored by: Amgen

Official(s) and/or principal investigator(s):
MD, Study Director, Affiliation: Amgen

This Phase 4 open-label, nonrandomized multicenter registry study is being conducted to evaluate the long-term safety of ENBREL(R) (etanercept) compared to methotrexate in patients aged 2 to 18 years with polyarticular-course or systemic-onset juvenile rheumatoid arthritis (JRA). Patients will be evaluated for a total of 3 years. The registry will include patients who have recently started and are currently receiving ENBREL alone, ENBREL in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARDs), methotrexate alone, or methotrexate in combination with other DMARDs. Approximately 600 patients will be enrolled at sites in the United States and Canada, with 400 patients receiving ENBREL and 200 receiving methotrexate without ENBREL. One group of patients will receive ENBREL by subcutaneous (SC) injection twice a week for up to 3 years and may continue taking other medicines such as prednisone or methotrexate. Another group will continue to receive methotrexate, either alone or in combination with DMARDs other than ENBREL. Candidates will be screened with a medical history and physical examination, including height, weight, and Tanner scores. A behavioral assessment, quality of life assessment, and physician's global assessment of disease activity will be performed. A blood test and joint evaluation will also be done. Both treatment groups will have on-study evaluations at baseline and months 3, 6, 9, 12, 18, 24, 30, and 36. Each follow-up visit will include a repeat of the screening assessments and an evaluation of adverse events or toxicity, including psychiatric and behavioral effects and new symptoms of autoimmune disorders. The two groups will be compared for safety, including effects on growth and development parameters. Patients will need to purchase or arrange the purchase of commercially available ENBREL. Patients entering the study during the period when ENBREL is in short supply will be able to obtain ENBREL after enrolling in the ENBREL Enrollment Program. Patients will receive ENBREL enrollment information at the time of registration into the study.

Official title: Phase IV Registry of Etanercept (ENBREL) in Children With Juvenile Rheumatoid Arthritis

Study design: Treatment, Non-Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Detailed description: Tumor necrosis factor (TNF) has been implicated in the disease process of rheumatoid arthritis (RA) in adults and children. ENBREL inhibits the binding of TNF to TNF receptors in the body, resulting in a significant reduction in inflammatory activity in RA. ENBREL has been approved by the FDA for reducing signs and symptoms and inhibiting structural damage in patients with moderately to severely active RA, and for reducing signs and symptoms in patients with moderately to severely active polyarticular-course JRA who have had an inadequate response to disease-modifying medicines. The purpose of this registry study is to evaluate the longer-term safety and effectiveness of ENBREL in children with polyarticular-course or systemic-onset JRA.

Minimum age: 2 Months. Maximum age: 18 Months. Gender(s): Both.

Criteria:

- Diagnosis of JRA by American College of Rheumatology (ACR) criteria. Disease onset

may have been systemic, polyarticular, or pauciarticular. - Disease course must be

polyarticular or systemic with active arthritis in 3 or more joints at the time of starting methotrexate alone, methotrexate in combination with other DMARDs, ENBREL alone, or ENBREL added to ongoing methotrexate or other DMARDs. (Alternately, patients may have their disease under control on one or more DMARDs with 0 active

joints at study entry.) - Duration of disease is not limited, but must have been long

enough for the patient to have been given an adequate trial of nonsteroidal

anti-inflammatory drugs (NSAIDs) and/or prednisone. - Patients in the methotrexate arm

must have started methotrexate within 6 months of enrollment in the registry. - At the

time of enrollment of patients into the ENBREL or methotrexate arm, a patient may be receiving methotrexate or other DMARDs provided that the DMARDs do not specifically inhibit TNF (e. g., infliximab, thalidomide, D2E7). Additional DMARDs are allowed after the first study visit. Patients may also be receiving NSAIDs and/or prednisone.

- Patients in the ENBREL arm must have started ENBREL within 6 months of enrollment

into the registry. An exception will be made for patients entering the registry from selected Immunex protocols where they may have received ENBREL for up to 1 year before enrolling in the registry. For these patients, the time of exposure will be counted

from receipt of the original first dose of ENBREL. - Parent or legal guardian must be

able to give informed consent. - Any patient of child-bearing or conceiving potential

must be practicing adequate contraception. Any of the following will exclude a patient

from this registry: - Pregnant or nursing female. - Previously received antibody to

TNF (anti-TNF), antibody to CD4 (anti-CD4), or diphtheria IL-2 fusion protein

(DAB-IL-2). - Participation in a study of an investigational drug or biologic other

than ENBREL requiring informed consent 6 months or less prior to study entry. -

Currently receiving TNF inhibitors other than ENBREL (e. g., infliximab, thalidomide,

D2E7), cyclophosphamide, experimental agents, or other biologic agents. - History of

alcohol or drug abuse that would interfere with the patient's ability to comply with

protocol requirements. - Prior malignancies if the patient has not been disease free

for at least 5 years. - Any serious acute or chronic medical condition other than JRA,

including chronic infection, that requires treatment or would compromise the patient's ability to cooperate with the protocol requirements.

http://www.immunex.com

AmgenTrials clinical trials website

Related publications:

Lovell DJ, Giannini EH, Reiff A, Cawkwell GD, Silverman ED, Nocton JJ, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Whitmore J, Finck BK. Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med. 2000 Mar 16;342(11):763-9.

Starting date: May 2000
Last updated: December 20, 2007