Biomarker-Linked Outcomes of Cellcept in Lupus Arthritis

This study has been completed.
Sponsor:
Collaborator:
New York University School of Medicine
Information provided by (Responsible Party):
Joan Merrill, MD, Oklahoma Medical Research Foundation
ClinicalTrials.gov Identifier:
NCT00594932
First received: January 4, 2008
Last updated: December 26, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention
Systemic Lupus Erythematosus
Arthritis
Drug: mycophenolate mofetil
Other: placebo
Drug: Mycophenolate mofetil

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Oklahoma Medical Research Foundation:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 27
Study Start Date: November 2006
Study Completion Date: April 2009
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
Other Names:
  • mycophenolate mofetil
  • mycophenolate
  • Cellcept
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.
Other: placebo
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)
Other Names:
  • inert tablet
  • oral placebo pill
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

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.

Baseline Characteristics:

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.

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.

  Eligibility

Ages Eligible for Study:   14 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of SLE by the 1995 modification of revised ACR criteria (includes antiphospholipid antibodies)
  2. BILAG A arthritis or BILAG B arthritis with at least 6 tender and 4 swollen joints at screening and baseline
  3. Stable prednisone dose at 20 mg of less for one month at baseline.
  4. If on antimalarials must be stable for at least one month at baseline
  5. If on NSAIDS must be on a stable regimen for at least one month but can be prn dosing
  6. Must be willing to withdraw from azathioprine or MTX at the time of screening.
  7. Between ages 14 and 70
  8. Women of childbearing potential must have a negative pregnancy test at screening and at each month during the study.
  9. 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:

  1. Inability to understand informed consent
  2. Drug or alcohol abuse within the past six months
  3. 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.
  4. Unstable medical condition that, in the opinion of the investigator would contraindicate study participation
  5. 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).
  6. Use of cyclosporine, leflunomide, cyclophosphamide or ay biologic agent within three months prior to screening.
  7. Participation in any clinical study of an investigational agent within three months of screening -
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00594932

Locations
United States, Oklahoma
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
Oklahoma Medical Research Foundation
New York University School of Medicine
Investigators
Principal Investigator: Joan T. Merrill, M.D. Oklahoma Medical Research Foundation
Study Chair: Robert Clancy, PhD New York University School of Medicine
  More Information

No publications provided

Responsible Party: Joan Merrill, MD, Head, Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation
ClinicalTrials.gov Identifier: NCT00594932     History of Changes
Other Study ID Numbers: OMRF 06-23, Aspreva Pharmaceuticals grant
Study First Received: January 4, 2008
Last Updated: December 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Oklahoma Medical Research Foundation:
lupus, arthritis, mycophenolate, biomarkers

Additional relevant MeSH terms:
Arthritis
Lupus Erythematosus, Systemic
Joint Diseases
Musculoskeletal Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Mycophenolate mofetil
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014