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Biomarker-Linked Outcomes of Cellcept in Lupus Arthritis

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ClinicalTrials.gov Identifier: NCT00594932
Recruitment Status : Completed
First Posted : January 16, 2008
Results First Posted : October 9, 2020
Last Update Posted : October 9, 2020
Sponsor:
Collaborator:
NYU Langone Health
Information provided by (Responsible Party):
Oklahoma Medical Research Foundation

Brief Summary:
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 or disease Intervention/treatment Phase
Systemic Lupus Erythematosus Arthritis Drug: mycophenolate mofetil Other: placebo Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Biomarker-Linked Outcomes of Cellcept in Lupus Arthritis
Study Start Date : November 2006
Actual Primary Completion Date : July 2008
Actual Study Completion Date : April 2009


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.
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
  • Cellcept

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.
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). 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:
  • inert tablet
  • oral placebo pill




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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.



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Ages Eligible for Study:   14 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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 -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00594932


Locations
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United States, Oklahoma
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
Oklahoma Medical Research Foundation
NYU Langone Health
Investigators
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Principal Investigator: Joan T. Merrill, M.D. Oklahoma Medical Research Foundation
Study Chair: Robert Clancy, PhD NYU Langone Health
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Responsible Party: Oklahoma Medical Research Foundation
ClinicalTrials.gov Identifier: NCT00594932    
Other Study ID Numbers: OMRF 06-23
Aspreva Pharmaceuticals grant ( Other Grant/Funding Number: Aspreva Pharmaceutical Investigator-Initiated Study )
First Posted: January 16, 2008    Key Record Dates
Results First Posted: October 9, 2020
Last Update Posted: October 9, 2020
Last Verified: October 2020
Keywords provided by Oklahoma Medical Research Foundation:
lupus, arthritis, mycophenolate, biomarkers
Additional relevant MeSH terms:
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Arthritis
Lupus Erythematosus, Systemic
Joint Diseases
Musculoskeletal Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Mycophenolic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action