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Biomarker-Linked Outcomes of Cellcept in Lupus Arthritis

Primary Purpose

Systemic Lupus Erythematosus, Arthritis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
mycophenolate mofetil
placebo
Sponsored by
Oklahoma Medical Research Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Lupus Erythematosus focused on measuring lupus, arthritis, mycophenolate, biomarkers

Eligibility Criteria

14 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 -

Sites / Locations

  • Oklahoma Medical Research Foundation

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm I:

Arm 2

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Arthritis Complete Response
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

Major Arthritis Response
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
Major and Partial Clinical Response
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.

Full Information

First Posted
January 4, 2008
Last Updated
October 7, 2020
Sponsor
Oklahoma Medical Research Foundation
Collaborators
NYU Langone Health
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1. Study Identification

Unique Protocol Identification Number
NCT00594932
Brief Title
Biomarker-Linked Outcomes of Cellcept in Lupus Arthritis
Official Title
Biomarker-Linked Outcomes of Cellcept in Lupus Arthritis
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
November 2006 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Oklahoma Medical Research Foundation
Collaborators
NYU Langone Health

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus, Arthritis
Keywords
lupus, arthritis, mycophenolate, biomarkers

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I:
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Arm 2
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Other Intervention Name(s)
mycophenolate, Cellcept
Intervention Description
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)
Intervention Type
Other
Intervention Name(s)
placebo
Other Intervention Name(s)
inert tablet, oral placebo pill
Intervention Description
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.
Primary Outcome Measure Information:
Title
Arthritis Complete Response
Description
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.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Major Arthritis Response
Description
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
Time Frame
3 months
Title
Major and Partial Clinical Response
Description
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.
Time Frame
3 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joan T. Merrill, M.D.
Organizational Affiliation
Oklahoma Medical Research Foundation
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Robert Clancy, PhD
Organizational Affiliation
NYU Langone Health
Official's Role
Study Chair
Facility Information:
Facility Name
Oklahoma Medical Research Foundation
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States

12. IPD Sharing Statement

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Biomarker-Linked Outcomes of Cellcept in Lupus Arthritis

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