Infliximab to Treat Children With Juvenile Rheumatoid Arthritis
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
|Official Title:||A Randomized Double Blind Controlled Intra-Patient Dose Escalation Phase II Trial of Infliximab in Pediatric Patients With Refractory Juvenile Rheumatoid Arthritis|
|Study Start Date:||January 2002|
|Study Completion Date:||October 2005|
Infliximab, a murine chimeric monoclonal antibody targeted against TNF-alpha has recently been licensed for the treatment of adult patients with established rheumatoid arthritis (RA). A double blind placebo controlled trial in children with juvenile rheumatoid arthritis (JRA) using a single dose fixed infusion regimen is currently ongoing. This dose finding study is designed to determine whether a clinically guided intravenous (iv) infusion regimen allowing for intra-patient dose escalation is superior in achieving a 70% clinical response to fixed dose administration of infliximab in children with a polyarticular course of JRA. We will model the pharmacokinetic profile in both phases of the study. We plan to enroll a maximum of 48 patients to allow for 36 patients to be randomized into the two treatment arms. In the first phase of the study all patients will receive a fixed dose of 5mg/kg/dose for a total of 3 infusions over 6 weeks (weeks 0, 2, 6). In the second phase at week 14, patients who have not achieved a 70% improvement will be randomized at a 2:1 ratio to either receive intra-patient dose escalation capped at 15mg/kg/dose every 8 weeks or continue to receive 5mg/kg/dose every 8 weeks in a blinded fashion. After 6 additional IV doses, patients will again be evaluated clinically, radiographically and serologically for clinical response. Patients who achieved a 70% response by week 14 will be kept on 5mg/kg/dose every 8 weeks for the trial duration of 62 weeks, but will not be included in the primary endpoint analysis. We also plan to evaluate patients endocrinologically and metabolically to determine the effect of TNF blockade on these systems.
|United States, Maryland|
|National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)|
|Bethesda, Maryland, United States, 20892|