Monoclonal Antibody Treatment for Systemic Lupus Erythematosus
This study will examine the safety and effects of the monoclonal antibody MRA in patients with systemic lupus erythematosus (SLE). Antibodies normally fight invading organisms. In autoimmune diseases, such as lupus, however, antibodies attack the body s own tissues. MRA is an antibody manufactured in the laboratory that blocks the action of interleukin-6 (IL-6), a substance that increases antibody production and is involved in inflammation that may cause organ damage in SLE.
Patients 18 years of age and older with moderately active systemic lupus erythematosus may be eligible for this 6-month study. Candidates will be screened with blood and urine tests, chest X-ray, electrocardiogram (EKG), and screening tests for certain cancers.
Participants will receive a total of up to seven infusions of MRA given every 2 weeks in the clinic. The MRA is infused over a period of about 1 hour through a catheter (thin plastic tube) inserted into an arm vein. Patients will be observed for 1 to 2 hours after each infusion for drug side effects. For the first and last infusions, patients will return to the clinic for blood tests 24 to 48 hours after the infusion. Additional tests may be done if medically indicated.
Three different doses of MRA will be used in three groups of patients. The first group (4 patients) will receive the lowest dose. If this dose is well tolerated, a second group (6 patients) will receive a higher dose. If this dose is also well tolerated, a third group (6 patients) will receive the highest study dose.
Patients will be evaluated at various intervals for up to 3 months after the last dose of MRA. The follow-up visits will include a review of the patient s medical history, a physical examination, blood and urine tests, and an EKG.
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I, Open-Labeled, Dose-Ascending Clinical Trial of Immunotherapy of MRA, A Humanized Anti-IL 6 Receptor Monoclonal Antibody, In Patients With Systemic Lupus Erythematosus|
- Safety/tolerance of MRA in pts w/SLE [ Time Frame: Wks 0,2,6,12,14,20 ]
- Clinical Pharmacokinetics of MRA [ Time Frame: Wks 0,2,6,12,14,20 ]
|Study Start Date:||September 2, 2002|
|Study Completion Date:||July 2, 2007|
|Primary Completion Date:||January 1, 2007 (Final data collection date for primary outcome measure)|
Interleukin-6 (IL-6) levels are elevated in both human and murine systemic lupus erythematosus (SLE). Blocking the action of IL-6 ameliorates disease activity in murine models of SLE. MRA is a humanized monoclonal antibody against the human IL-6 receptor. Data from clinical trials in patients with rheumatoid arthritis suggest that MRA may be a safe agent to block the effect of IL-6 and therefore may be used to evaluate the effects of IL-6 blockade in patients with SLE. In this open label, dose-escalating, Phase I study, up to 27 subjects with moderately active SLE may be enrolled. Subjects will be treated with bi-weekly infusions of one of three doses (2mg/kg, 4 mg/kg or 8 mg/kg) of MRA for 12 weeks and followed for 8 weeks after the last dose. Patients with or without lupus nephritis may be enrolled if they do not require immediate immunosuppressive therapy other than prednisone at doses of less than or equal to 0.3 mg/kg/day. Safety will be evaluated using standard clinical and laboratory parameters. To assess the potential effect of MRA on SLE, clinical and laboratory evaluations and surrogate markers of inflammation and disease activity, such as autoantibody production and lymphocyte subsets, will be compared before and after the treatment. Patients who either do not tolerate the drug or those who have a clinically significant increase in their disease activity that does not respond to moderate doses of corticosteroids will be withdrawn from the protocol.
If this regimen is shown to be well tolerated, studies of efficacy will be planned. This agent is expected to be devoid of the most common toxicities of therapies commonly used in the treatment of SLE, such as myelosuppression, amenorrhea and osteoporosis.
This study will provide important preliminary information about the safety and possible effect of IL-6 blockade in SLE patients, an intervention that has been successful in animal models but has not yet been studied in humans.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00046774
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Sarfaraz A Hasni, M.D.||National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)|