Infliximab to Treat Children With Juvenile Rheumatoid Arthritis

NCT00029042 | Terminated Phase 2

• 2 other identifiers: 02008102-AR-0081
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine whether a stepwise increase of the drug infliximab (Remicade® (Registered Trademark)) controls juvenile rheumatoid arthritis more effectively than a fixed dose. It will look at the safety and effectiveness of increasing the dose to a maximum of 15mg/kg body weight per dose, examining the drug's effect on bone and cartilage, and whether it can improve abnormal growth, metabolism and hormones. Infliximab is approved for treating adults with rheumatoid arthritis and Crohn's disease. Children between 4 and 17 years of age with active juvenile rheumatoid arthritis who do not respond adequately to standard therapy may be eligible for this study. Participants will receive nine infusions of infliximab during this 62-week study. The drug is given intravenously (IV, into a vein) over 2 hours. The first three infusions will be at a dose of 5 mg/kg of body weight. Children who improve on this regimen will receive another 6 infusions at the same dose. Children who do not significantly improve on 5 mg/kg at the end of 6 weeks (the third infusion) may continue with phase 2 of the study, in which they will be randomly assigned to receive either: 1) 6 additional doses of the drug at 5 mg/kg per dose, or 2) a gradually increased dose to a maximum of 15 mg/kg. In addition, all children will continue to take methotrexate at the same dose as when they entered the study. Participants will visit the NIH Clinical Center 12 times (about every 8 weeks) during the study for the following tests and procedures:

• History and physical examination, including a complete joint exam
• Puberty assessment - breast development in girls, testicle size in boys, and pubic hair
• Height and weight measurements Children will have imaging studies (x-rays, MRI and Dexa scan) at the beginning and end of the study and will collect a 24-hour urine sample before each infliximab infusion. Patients may elect to have an endocrine evaluation. This involves Clinical Center hospitalizations for 1-1/2 days on visits 1, 4 and 12. Small amounts of blood will be drawn every 20 minutes (through an indwelling catheter to avoid multiple needle sticks) for 8 hours while the child sleeps. The blood will be examined for the normal rhythm of growth hormone and other substances in the body and how they are affected by arthritis. Participants will complete a questionnaire once a year for 2 years to provide information on their health status and any problems that might be related to the study drug.

Conditions

Juvenile Rheumatoid Arthritis

Keywords

MRI; Inflammation; Joint Disability; Imaging; Biologic Therapy; Rheumatoid Arthritis; Juvenile Rheumatoid Arthritis; JRA; Children; Joints; Joint Inflammation

Interventions

Infliximab DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: Patients must be less than 18 years of age and greater than or equal to 4 years of age.
• Diagnosis of pauciarticular, polyarticular or systemic onset JRA according to the 'Criteria for the diagnosis of Juvenile Rheumatoid Arthritis' with evidence of active disease including all of the features within each category:
• Pauciarticular JRA (if patients continue to develop a polyarticular course):
• active synovitis involving at least 4 swollen joints
• tenderness or pain on movement of greater than 4 involved joints
• Polyarticular JRA:
• active synovitis involving at least 4 swollen joints
• tenderness or pain on movement of greater than 4 swollen joints
• elevated acute phase reactants (ESR greater than 20mm/hr or CRP greater than 0.8mg/dl)
• Systemic onset JRA (if patients develop a polyarticular course):
• active synovitis involving at least 4 swollen joints
• tenderness or pain on movement of greater than 4 swollen joints
• elevated acute phase reactants (ESR greater than 20mm/hr or CRP greater than 0.8mg/dl)
• Disease onset at age less than16 years.
• Informed Consent: All parent(s) or their legal guardian(s) must sign a document of informed consent indicating their understanding of the investigational nature and the risks of this study before any protocol related studies are performed (this does not include routine laboratory tests or imaging studies required to establish eligibility). Pediatric patients will be included in all discussions in order to obtain verbal or written assent.

You may not qualify if:

• Pregnant women and nursing mothers, sexually active men or women of childbearing potential not practicing birth control. (Sexually active subjects of childbearing or child-fathering potential must be willing to use an acceptable form of birth control, which includes oral contraceptives, barrier methods with spermicides, intrauterine devices (IUD's), medroxyprogesterone acetate (Depo-Provera), progestin implants or intrauterine system or surgical sterilization. All post-menarche females or females greater than or equal to 12 years must test negative on a urine pregnancy test. Sexually active males and females will be instructed to use condoms).
• Patients with other rheumatic diseases that may confound the analysis including but not limited to Lyme disease, post streptococcal reactive arthritis, psoriatic arthritis, spondyloarthropathy, systemic lupus erythematosus, other infectious or reactive arthritis, or Reiter's syndrome.
• Previous treatment with iv infliximab at doses greater than 3mg/kg/dose every 8 weeks.
• Poor venous access.
• Treatment with any monoclonal antibody in the past other than infliximab.
• Allergy to murine-derived products.
• Previous history or ongoing infection with tuberculosis or pneumocystis and patients with acute or chronic infections requiring anti-microbial therapy, serious viral infections (e.g. hepatitis, herpes zoster, CMV or HIV) or fungal infections or history of recurrent serious bacterial infections.
• History of live vaccinations within the past 3 months.
• Confounding medical illness that in the judgment of the investigators would pose added risk for study participants (e.g. chronic hepatic, hematologic, neurologic, renal, or pulmonary disease).
• Past medical history or be currently diagnosed with any solid organ or hematologic malignancies including lymphoproliferative diseases and leukemias.
• History of substance abuse within the past 5 years.
• History of psychiatric illnesses that in the opinion of psychiatric consultants would pose added risk for study participants.
• Pre-existing or recent onset of demyelinating disorders or type I diabetes.

Sponsors & Collaborators

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): lead

Study Sites (1)

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

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Conditions

Arthritis, Juvenile; Inflammation; Arthritis, Rheumatoid; Arthritis

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: January 4, 2002
• First Posted: January 7, 2002
• Study Start: January 1, 2002
• Study Completion: October 1, 2005
• Last Updated: August 27, 2008

Record last verified: 2008-08

Locations

US (1)