Biomarker-Linked Outcomes of Cellcept in Lupus Arthritis
We hypothesize that mycophenolate mofetil(Cellcept)is safe and effective for lupus arthritis. In this study, patients with lupus will be randomly assigned to receive mycophenolate mofetil or placebo (inert pills) for three months. At the end of three months all patients will receive mycophenolate mofetil for three additional months. The effectiveness on arthritis and other symptoms of lupus will be measured by joint counts and by the BILAG instrument (a measure of overall lupus disease activity. Additionally special blood tests aimed at understanding the biologic effects of mycophenolate mofetil will also be performed at some visits. The primary outcome measurement will be the safety and effectiveness of this treatment (as compared to placebo) at the three month point. The trial will continue in a blinded fashion (neither the investigator or the participants know who is getting mycophenolate and who is getting placebo) until 24 patients have completed the first three months of the protocol.
Systemic Lupus Erythematosus
Drug: mycophenolate mofetil
Drug: Mycophenolate mofetil
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Biomarker-Linked Outcomes of Cellcept in Lupus Arthritis|
- Complete response (</= 0.25 tender and swollen joints at baseline and BILAG C or D score in Musculoskeletal system) at three months, comparing treatment to placebo group [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Adverse events assessed by organ system comparing treatment vs placebo [ Time Frame: 3 months and 6 months ] [ Designated as safety issue: Yes ]
- Changes in inflammatory markers (surface expression of cell activation markers and circulating cytokines) in response to Cellcept vs placebo [ Time Frame: 3 months and 6 months ] [ Designated as safety issue: No ]
- Special Ancillary study: Effects of treatment vs placebo on activation of circulating endothelial cells and nitric oxide (in collaboration with Dr. Robert Clancy of New York University Medical Center) [ Time Frame: 3 months and 6 months ] [ Designated as safety issue: No ]
- Expression of interferon alpha inducible gene panel and inosine-monophosphate dehydrogenase II expression in response to mycophenolate vs placebo [ Time Frame: 3 months and 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||November 2006|
|Study Completion Date:||April 2009|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
Experimental: Arm I:
Participants randomly assigned to Arm I will receive mycophenolate mofetil in ascending doses during Month 1, and 3 grams/day (or less if there are tolerance issues) for Months 2 through 6.
Drug: mycophenolate mofetil
First treatment month: mycophenolate mofetil ascending doses orally Second treatment month to end of study: mycophenolate mofetil 3 gms/day (or less if tolerance issues arise)
Placebo Comparator: Arm 2a
Patients Randomly Assigned to Arm 2 will enter Arm 2a for three months as a placebo comparator. The placebo treatment will be structured so that they will undergo the same type of dosing in Month 1 that the ascending dose patient from Arm 1 undergo, but will have placebo in both bottles of pills. At the end of three months, after assessment of primary outcome, these patients enter Arm 2b which is a treatment arm.
oral placebo will be given in ascending "doses" during the first month and at full "dose" during the second and third month (or at lower "dose" if tolerance issues warrant)
Active Comparator: Arm 2b Open Lable Mycophenolate Mofetil
Arm 2b begins for patients in Arm 2 after three months. They will receive ascending doses of mycophenolate for the first month (which is Month 4 of the study). This will still be blinded since patients in Arm 1 will be undergoing an identical ascending dose regimen during this month, except that there will be active treatment in both bottles. At the end of Month 4 all patients will know that they are on full dose of 3 gms/day mycophenolate (or a lower dose if there are tolerance issues).
Drug: Mycophenolate mofetil
Please see the Arm Description
Other Name: Cellcept
Patients and Methods:
27 patients with active BILAG B or A arthritis, with at least 6 swollen and 6 tender joints entered a six month study of MMF vs placebo for three months followed by open label MMF. 14 patients (12 women and 2 men) received placebo at baseline and 13 patients (11 women and 2 men) received MMF. Primary Outcome was Major Clinical Response at 3 months, then all patients received open label Cellcept for another 3 months. Blood was drawn for safety, lupus disease activity measures and exploratory Biomarkers, Joint counts were performed monthly. At baseline background DMARDs were stopped. Plaquenil was allowed. All patients received 160 mg depomedrol at baseline and were allowed 80 mg shots at subsequent months after blood draws and procedures had been completed.
At entry into the study, there was no difference between MMF and placebo in: age, gender, ethnicity, number of ACR criteria for lupus, or number of swollen and tender joints.
DEFINITION of RESPONSE
Prespecified Primary Endpoint: Complete Clinical Response:
BILAG C in musculoskeletal by Week 12 and decrease to 0.25 or less of tender +swollen jt counts
Prespecified Secondary Endpoint: Partial response:
One letter drop in musculoskeletal by Week 12 OR decrease to 0.5 or less tender + swollen jt counts
Exploratory Measure (not prespecified): Major Clinical Response:
BILAG C in musculoskeletal by Week 12 and decrease to 0.5 or less of tender +swollen jt counts. (In the primary analysis the one patient who met this endpoint was designated as a partial responder since those prespecified criteria were also met.
Does not meet above criteria for complete or partial response
Additional Measures: (prespecified secondary endpoints) included joint counts, changes in BILAG and SLEDAI and physician and patient global assessments.
|United States, Oklahoma|
|Oklahoma Medical Research Foundation|
|Oklahoma City, Oklahoma, United States, 73104|
|Principal Investigator:||Joan T. Merrill, M.D.||Oklahoma Medical Research Foundation|
|Study Chair:||Robert Clancy, PhD||New York University School of Medicine|