- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00594932
Biomarker-Linked Outcomes of Cellcept in Lupus Arthritis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
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.
Non response:
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Oklahoma
-
Oklahoma City, Oklahoma, United States, 73104
- Oklahoma Medical Research Foundation
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of SLE by the 1995 modification of revised ACR criteria (includes antiphospholipid antibodies)
- BILAG A arthritis or BILAG B arthritis with at least 6 tender and 4 swollen joints at screening and baseline
- Stable prednisone dose at 20 mg of less for one month at baseline.
- If on antimalarials must be stable for at least one month at baseline
- If on NSAIDS must be on a stable regimen for at least one month but can be prn dosing
- Must be willing to withdraw from azathioprine or MTX at the time of screening.
- Between ages 14 and 70
- Women of childbearing potential must have a negative pregnancy test at screening and at each month during the study.
All participants (male and female) must, if fertile, agree to practice contraception during the entire course of the study. This may include barrier, oral contraceptives, depo-provera, intrauterine device and/or abstinence.
-
Exclusion Criteria:
- Inability to understand informed consent
- Drug or alcohol abuse within the past six months
- In the opinion of the investigator, it is not likely the patient can comply with the protocol for any reason, or participation in the protocol is not in the patient's best interest.
- Unstable medical condition that, in the opinion of the investigator would contraindicate study participation
- History of malignancy (except for basal cell carcinoma at any time and/or cervical cancer or squamous cell cancer at least five years previous to screening).
- Use of cyclosporine, leflunomide, cyclophosphamide or ay biologic agent within three months prior to screening.
- Participation in any clinical study of an investigational agent within three months of screening -
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: 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.
During Month 1 these participants receive the same number of pills as every other month, but with ascending doses of mycophenolate mofetil and descending numbers of placebo pills.
Week one for a total of 1.5 gm/day of mycophenolate mofetil, Week two 2.0 gm/day, Week three 2.5 gm/day and Week 4 3 gm/day.
Dose can be held or decreased for tolerance issues at any time.
|
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)
Other Names:
|
PLACEBO_COMPARATOR: Arm 2
Patients Randomly Assigned to Arm 2 will receive 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 open label treatment for three more months.
During the fourth month this group continues to receive the same number of pills as they received before, with ascending doses of mycophenolate mofetil given vs descending placebo pills so that their induction is the same as those in Arm 1 at the first month.
|
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).
During the fourth month mycophenolate mofetil will be given in ascending doses to 3 gms/day (or less if tolerance issues arise) and continues until the end of the study at 6 months.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Arthritis Complete Response
Time Frame: 3 months
|
Complete response at three months (This is defined as </= 0.25 of the total tender plus swollen joints observed at baseline and British Isles Lupus Assessment Group (BILAG) index C (mild) or D (no longer present) score in the Musculoskeletal system), comparing treatment to placebo group as complete responder or not complete responder.
This was an intent to treat analysis so dropouts were counted as non-responders.
|
3 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Major Arthritis Response
Time Frame: 3 months
|
This is defined as at least a 50% reduction in tender + swollen joint counts and severity rated as mild as defined by the British Isles Lupus Assessment Group Index
|
3 months
|
Major and Partial Clinical Response
Time Frame: 3 Months
|
Those meeting the Criteria for Major or Complete Clinical Response as listed in the preceding endpoints or who meet criteria for partial response defined as at least a 25% decrease in tender and swollen joint count and improvement of at least one severity rating for arthritis as at least one level on the British Isles Lupus Assessment Group Index.
|
3 Months
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Joan T. Merrill, M.D., Oklahoma Medical Research Foundation
- Study Chair: Robert Clancy, PhD, NYU Langone Health
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Connective Tissue Diseases
- Arthritis
- Lupus Erythematosus, Systemic
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antitubercular Agents
- Antibiotics, Antitubercular
- Mycophenolic Acid
Other Study ID Numbers
- OMRF 06-23
- Aspreva Pharmaceuticals grant (OTHER_GRANT: Aspreva Pharmaceutical Investigator-Initiated Study)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Arthritis
-
Northumbria Healthcare NHS Foundation TrustUniversity of YorkRecruitingKnee Arthritis | Hip ArthritisUnited Kingdom
-
MedShape, IncOrthopedic Foot and Ankle Center, Ohio; CurveBeam LLCRecruitingAnkle Arthritis | Arthritis FootUnited States
-
MedShape, IncUniversity of Alabama at BirminghamRecruitingAnkle Arthritis | Foot ArthritisUnited States
-
University of Alabama at BirminghamMedShape, IncRecruiting
-
MedShape, IncThe University of Texas Medical Branch, GalvestonRecruitingAnkle Arthritis | Foot ArthritisUnited States
-
Chang Gung Memorial HospitalNot yet recruitingArthritis Knee | Arthritis HipTaiwan
-
MedShape, IncSaint Alphonsus Medical GroupUnknownAnkle Arthritis | Foot ArthritisUnited States
-
Saint Alphonsus Regional Medical CenterCompletedArthritis Knee | Arthritis of HipUnited States
-
Sunnybrook Health Sciences CentreUniversity Health Network, Toronto; University of TorontoCompleted
-
Smith & Nephew, Inc.TerminatedRheumatoid Arthritis | Traumatic Arthritis | Osteo Arthritis ShouldersUnited States
Clinical Trials on mycophenolate mofetil
-
University of GiessenNovartis; Hoffmann-La Roche; Astellas Pharma Inc; Heidelberg UniversityCompletedPolyomavirus InfectionsGermany
-
Novartis PharmaceuticalsCompletedRenal TransplantationUnited States
-
Nanjing University School of MedicineCompletedNephritis | Henoch-Schoenlein PurpuraChina
-
Nanjing University School of MedicineCompletedVasculitis | Anti-Neutrophil Cytoplasmic AntibodyChina
-
Children's Hospital of Fudan UniversityShanghai Children's Hospital; Shanghai Children's Medical Center; Xinhua Hospital...WithdrawnSteroid-Dependent Nephrotic Syndrome | Frequently Relapsing Nephrotic SyndromeChina
-
Teva Branded Pharmaceutical Products R&D, Inc.ParexelTerminatedStable Renal Transplant Recipients
-
Panacea Biotec LtdCompletedHealthy VolunteersIndia
-
Panacea Biotec LtdCompletedHealthy VolunteersIndia
-
Fred Hutchinson Cancer CenterUniversity of WashingtonCompleted
-
Samsung Medical CenterUnknown