Randomized MMF Withdrawal in Systemic Lupus Erythematosus (SLE) (ALE06)

An Investigator-Initiated, Phase II, Randomized, Withdrawal Study of Mycophenolate Mofetil (MMF) in Patients With Stable, Quiescent Systemic Lupus Erythematosus (SLE)

This trial seeks to describe the effect of withdrawal from mycophenolate mofetil (MMF) on risk of clinically significant disease reactivation in quiescent SLE patients who have been on long-term MMF therapy.

Study Overview

• Status: Terminated
• Conditions: Systemic Lupus Erythematosus; SLE
• Intervention / Treatment: Drug: Mycophenolate Mofetil; Drug: Hydroxychloroquine or Chloroquine; Drug: Prednisone

Detailed Description

Participants who have had inactive disease for at least 24 weeks will be enrolled. Half the subjects will continue on MMF and half the subjects will be tapered off their MMF within 12 weeks. All subjects will continue hydroxychloroquine and small doses of prednisone as needed. Subject visits to assess endpoints will occur every 4 weeks from Day 0 through Week 24 and then at Weeks 32, 40, 48, and 60.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • San Diego, California, United States, 92093-0943
      • UCSD
    • San Francisco, California, United States, 94143-0633
      • UCSF School of Medicine
  • Colorado
    • Denver, Colorado, United States, 80204
      • University of Colorado
  • Florida
    • Miami, Florida, United States, 33136
      • University Of Miami Hospitals And Clinics
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637-1426
      • University of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New York
    • Manhasset, New York, United States, 11025
      • Feinstein Institute for Medical Research
    • New York, New York, United States, 10016
      • New York University, Langone Medical Center
    • New York, New York, United States, 10021
      • Weill Cornell Medical College: Hospital for Special Surgery - Rheumatology Division
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Medical Research Foundation
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State University
  • South Carolina
    • Charleston, South Carolina, United States, 29412
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able and willing to give written informed consent and comply with requirements of the study;
2. Age 18 - 70 years, inclusive, at randomization;
3. Diagnosis of SLE, per the American College of Rheumatology (ACR) criteria;
4. m-SLEDAI score < 4 at screening visit (SLEDAI score without serologies);
5. Physician Global Assessment (0-3) score of 1 or less at screening visit;
6. On a stable dose of MMF (1000-3000 mg/day) for at least 12 weeks prior to randomization;

7. Total duration of stable or decreasing MMF therapy must be at least:

   • two years for subjects initiating MMF for renal indications (with or without concurrent extra-renal manifestations), or
   • one year for subjects initiating MMF for extra-renal indications.

8. If the subject is on prednisone or other corticosteroid, the following criteria must be met:

   • the dose may not exceed 10 mg/day (or its equivalent) for the 12 weeks prior to randomization; however, temporary (up to 4 total days) increases, not to exceed 20mg/day, are permitted;
   • the dose must be held stable for the four weeks prior to randomization (no temporary increases within 4 weeks of randomization are permitted).
9. If the subject has a history of B cell depleting therapy within the past 3 years, presence of CD19 positive cells must be documented within 12 weeks prior to screening;
10. On maintenance HCQ or chloroquine at a stable dose for at least 12 weeks prior to randomization.

Exclusion Criteria:

1. A history of life-threatening neuropsychiatric SLE within 1 calendar year prior to randomization;

2. Any of the following laboratory abnormalities at the screening visit:

   • Proteinuria as defined by a spot protein/creatinine ratio > 1.0 mg/mg;
   • Serum creatinine > 2.0 mg/dL;
   • Transaminases > 2.5x the upper limit of normal (ULN);
   • Hemoglobin < 9 g/dL, unless the subject has documented hemoglobinopathy;
   • White blood count (WBC) < 2000/mm^3 (equivalent to < 2 x10^9/L);
   • Neutrophils < 1000/mm^3 (equivalent to < 1 x10^9/L); or
   • Platelet count < 75,000/mm^3 (equivalent to < 75 x 10^9/L).
3. Prednisone > 25 mg/day (or its equivalent) within 24 weeks prior to randomization for lupus activity;
4. Concomitant immunosuppressants including but not limited to azathioprine, methotrexate, 6-mercaptopurine, leflunomide, calcineurin inhibitors, anti-tumor necrosis factor agents within 12 weeks prior to randomization;
5. Plasmapheresis or IV immunoglobulin within 12 weeks prior to randomization;
6. Cyclophosphamide therapy within 24 weeks prior to randomization;
7. Concomitant therapy with belimumab within 24 weeks prior to randomization;
8. B cell depleting therapy within two calendar years of randomization;
9. Experimental therapy within the 24 weeks, or five half-lives of the agent, whichever is longer, prior to randomization;
10. Solid organ or stem cell transplantation;
11. Identified definitive diagnosis of another autoimmune disease that may require immunosuppression for treatment, including but not limited to: rheumatoid arthritis, scleroderma, primary Sjogren's syndrome, primary vasculitis, psoriasis, multiple sclerosis, ankylosing spondylitis, and inflammatory bowel disease.
12. Chronic infections including, but not limited to, human immunodeficiency virus (HIV), active tuberculosis (TB), currently receiving therapy)), hepatitis B or hepatitis C, or latent systemic fungal infection;

13. At or within 12 weeks of screening:

    • a history of or current positive purified protein derivative (PPD) (> 5 mm induration regardless of prior Bacillus Calmette-Guérin (BCG) vaccine administration) or positive QuantiFERON unless documentation exists of completion of at least one month of prophylaxis for latent TB or completed treatment for active TB; or
    • an indeterminate QuantiFERON® unless followed by a subsequent negative PPD or negative QuantiFERON.
14. History of malignancy within the last five years, except for resected basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ cervical cancer Grade I;
15. Pregnant or lactating, or intention to pursue pregnancy within three months after the completion of the study;
16. Unable or unwilling to use reliable methods of contraception, as outlined in the Mycophenolate REMS (e.g., Risk Evaluation and Mitigation Strategy), from four weeks prior to randomization to 6 weeks after completion of the study. This criterion applies to females of reproductive potential. (Reference: Mycophenolate REMS, Program Resources and Educational Materials, Information for Patients, What are my birth control options? Access the link at: (https://www.mycophenolaterems.com/PatientOverview.aspx).
17. Drug or alcohol abuse within one calendar year of randomization;
18. Other medical or psychiatric conditions that the investigator feels would place the subject at special risk by participation in this protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Mycophenolate Mofetil Withdrawal; These subjects will taper off MMF per the protocol-specified schedule over 12 weeks and remain off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation is met, whichever comes first).	Drug: Mycophenolate Mofetil; Subjects will enter the trial on 1000-3000 mg/day of MMF and will be randomized to remain on MMF treatment or to be tapered off MMF within 12 weeks.; Other Names: MMF; Drug: Hydroxychloroquine or Chloroquine; Subjects will be on concurrent anti-malarial agents (hydroxychloroquine or chloroquine). Hydroxychloroquine is approved by the FDA for the treatment of SLE. Hydroxychloroquine has been shown to help prevent flare in SLE, and to improve skin and musculoskeletal activity in particular.Even lupus nephritis outcomes appear improved on a background of hydroxychloroquine therapy; Other Names: Plaquenil®; Chloroquine Phosphate®; Drug: Prednisone; Once the subject is randomized into the trial, the prednisone (or other corticosteroid) dose must be stable through Week 36 (24 weeks following protocol taper of MMF), in the absence of flares as described in Section 3.2 of the study protocol, Description of Primary Endpoint. Further taper of prednisone after that point is by the investigator's discretion based on the subject's clinical status.; Other Names: corticosteroid
ACTIVE_COMPARATOR: Mycophenolate Mofetil Maintenance; These subjects will continue MMF treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).	Drug: Mycophenolate Mofetil; Subjects will enter the trial on 1000-3000 mg/day of MMF and will be randomized to remain on MMF treatment or to be tapered off MMF within 12 weeks.; Other Names: MMF; Drug: Hydroxychloroquine or Chloroquine; Subjects will be on concurrent anti-malarial agents (hydroxychloroquine or chloroquine). Hydroxychloroquine is approved by the FDA for the treatment of SLE. Hydroxychloroquine has been shown to help prevent flare in SLE, and to improve skin and musculoskeletal activity in particular.Even lupus nephritis outcomes appear improved on a background of hydroxychloroquine therapy; Other Names: Plaquenil®; Chloroquine Phosphate®; Drug: Prednisone; Once the subject is randomized into the trial, the prednisone (or other corticosteroid) dose must be stable through Week 36 (24 weeks following protocol taper of MMF), in the absence of flares as described in Section 3.2 of the study protocol, Description of Primary Endpoint. Further taper of prednisone after that point is by the investigator's discretion based on the subject's clinical status.; Other Names: corticosteroid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Clinically Significant Disease Reactivation by Week 60	Disease reactivation requires:1) SELENA-SLEDAI mild/moderate or severe flare,and 2) Increased immunosuppressive therapy on a sustained basis,defined by one of the following criteria:a) Sustained activity:Significant prolonged SLE flare requiring steroid increase/burst to ≥15 mg/day prednisone (or equivalent) for >4 weeks.b) Frequent relapsing/remitting:Participant flares requiring an increase/burst of steroids and is successfully tapered to <15 mg/day within 4 weeks, but this occurs on >2 occasions, or IA, IM or IV steroids on more than1 occasion.c)Clinical activity of sufficient severity to warrant resumption of/increased dose of MMF or addition of other major immunosuppressive including AZA or MTX.Regardless of steroid use, if the investigator observes disease activity of sufficient severity to warrant resumption, addition or increase in dosage of major immunosuppressant in the setting of a SELENA-SLEDAI flare, participant has met the primary endpoint.Risk difference also included	Baseline (Treatment Randomization) to Week 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Clinically Significant Disease Reactivation	The time to clinically significant disease reactivation was defined as the time from Baseline/Day 0 to the date of the first Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) assessment that met (or went on to meet) the criteria for clinically significant disease reactivation. Time to clinically significant disease reactivation was defined in study weeks as: date of SELENA-SLEDAI assessment that met reactivation criteria minus (-) baseline date.	Baseline (Treatment Randomization) to Week 60
Number of Participants Experiencing a Mild/Moderate or Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60	The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes mild/moderate or severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.	Baseline (Treatment Randomization) to Week 60
Number of Participants Experiencing a Mild/Moderate or Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 Within the Lupus Nephritis Subgroup	The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.	Baseline (Treatment Randomization) to Week 60
Number of Participants Experiencing a Mild/Moderate or Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 Within the Non-Lupus Nephritis Subgroup	The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.	Baseline (Treatment Randomization) to Week 60
Number of Participants Experiencing a Mild/Moderate or Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 in the Baseline MMF<2000 mg/Day Subgroup	The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included. MMF: mycophenolate mofetil	Baseline (Treatment Randomization) to Week 60
Number of Participants Experiencing a Mild/Moderate or Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 in the Baseline MMF ≥ 2000 mg/Day Subgroup	The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included. MMF: mycophenolate mofetil	Baseline (Treatment Randomization) to Week 60
Number of Participants Experiencing a Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60	The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.	Baseline (Treatment Randomization) to Week 60
Number of Participants Experiencing a Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 Within the Lupus Nephritis Subgroup	The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.	Baseline (Treatment Randomization) to Week 60
Number of Participants Experiencing a Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 Within the Non-Lupus Nephritis Subgroup	The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.	Baseline (Treatment Randomization) to Week 60
Number of Participants Experiencing Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 in the Baseline MMF <2000 mg/Day Subgroup	The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included. MMF: mycophenolate mofetil	Baseline (Treatment Randomization) to Week 60
Number of Participants Experiencing Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 in the Baseline MMF ≥ 2000 mg/Day Subgroup	The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included. MMF: mycophenolate mofetil	Baseline (Treatment Randomization) to Week 60
Time to First Mild/Moderate or Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare	The time to first mild/moderate or severe SELENA-SLEDAI flare was defined as the time from Baseline/Day 0 to the date of the first mild/moderate or severe SELENA-SLEDAI flare. Time to SELENA-SLEDAI flare was defined in study weeks as: date of SELENA-SLEDAI flare minus (-) baseline date. The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes mild/moderate or severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE.	Baseline (Treatment Randomization) to Week 60
Time to First Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare	The time to first severe SELENA-SLEDAI flare was defined as the time from Baseline/Day 0 to the date of the first severe SELENA-SLEDAI flare. Time to severe SELENA-SLEDAI flare was defined in study weeks as: date of SELENA-SLEDAI flare minus (-) baseline date. The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes mild/moderate or severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE.	Baseline (Treatment Randomization) to Week 60
Number of Participants Experiencing Any British Isles Lupus Assessment Group (BILAG) A Flare by Week 60	The BILAG assesses participants on a variety of disease activity criteria in nine body system categories (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal, and hematological). Each category is scored as an A, B, C, or D/E, where A indicates most severe disease activity and D/E indicates inactive/no disease activity. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.	Baseline (Treatment Randomization) to Week 60
Number of Participants in the Lupus Nephritis Subgroup Experiencing a British Isles Lupus Assessment Group (BILAG) A Renal Flare by Week 60	The BILAG assesses participants on a variety of disease activity criteria in nine body system categories (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal, and hematological). Each category is scored as an A, B, C, or D/E, where A indicates most severe disease activity and D/E indicates inactive/no disease activity. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.	Baseline (Treatment Randomization) to Week 60
Change From Baseline in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Disease Damage Index for Systemic Lupus Erythematosus (SLICC/DI): Total Score	The SLICC/DI measures accumulated damage that has occurred since the onset of systemic lupus erythematosus (SLE), regardless of cause, in 12 organ systems. SLE damage is defined as an irreversible change in an organ or system that has been present for at least 6 months. The SLICC/DI includes 39 areas of damage in 12 domains, where each item is rated as present or absent; if evidence of damage is present for a particular item, it is given a score of 1. Some items are scored with 2 or 3 points in the case of recurring events or end stage renal disease. The SLICC/DI total score will be computed as the sum of all scores for items indicated as present; scores can range from 0 to 45. Higher scores indicate more damage.	Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60
The Addition of Aggressive Adjunctive Therapy to Mycophenolate Mofetil (MMF) or Change in MMF Therapy to Cytotoxic Drug Due to Flare by Week 60	The addition of aggressive adjunctive therapy could include intravenous (IV) immunoglobulin or rituximab at any point during the participant's study participation. A change in therapy to cytotoxic drug due to flare could include drugs such as cyclophosphamide, etc. A blinded list of study medications was reviewed to identify the addition of aggressive adjunctive therapy or cytotoxic drugs.	Baseline (Treatment Randomization) to Week 60
Cumulative Systemic Steroid Dose by Week 60	Steroids include medications that code to a medication class which includes the terms "glucocorticoid" or "corticosteroid". Systemic steroids will include any of these steroids that are taken by mouth (PO), intravenous (IV), or intramuscular (IM). Total cumulative systemic steroid dose, in milligrams, was summarized over the 60 week study period, or until early study termination, for each participant.	Baseline (Treatment Randomization) to Week 60
Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT-F) Fatigue Scale (FS): Total Score	FACIT-Fatigue scale (FS) is a 13-item questionnaire completed by the patient (participant), that provides a measure of fatigue/quality of life, with a 7-day recall period. The participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-FS score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status. A decrease in the FACIT-FS score reflects worse fatigue/quality of life.	Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60
Change From Baseline in the Short Form Health Survey (SF-36) Physical Functioning (PF) Score	The SF-36 is a 36-item, patient-reported survey of patient health. Higher scores indicate better outcomes while lower scores indicate more disability. The PF score is used to assess changes in physical functioning. It is scaled from 0 to 100 with a score of 0 equivalent to maximum disability and a score of 100 equivalent to no disability.	Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60
Change From Baseline in the Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score	The SF-36 is a 36-item, patient-reported survey of patient health. Higher scores indicate better outcomes while lower scores indicate more disability. The Physical Component Score is comprised of the Physical Functioning Scale, the Role-Physical Scale, the Bodily Pain Scale, and the General Health Scale. It is scaled from 0 to 100 with a score of 0 equivalent to maximum disability and a score of 100 equivalent to no disability.	Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60
Change From Baseline in the Lupus Quality of Life (QoL)Score	The Lupus QoL assessment is a 34 item questionnaire across 8 domains that is designed to find out how systemic lupus erythematosus (SLE) affects a participant's life over the preceding 4 weeks. Scores range from 0 (worst QoL) to 100 (best QoL). Domains include physical health, pain, planning, intimate relationships, burden to others, emotional health, body image, and fatigue.	Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60
Time From Clinically Significant Disease Reactivation to Improvement in British Isles Lupus Assessment Group (BILAG) From Maximum Level During Flare	For each participant who experienced disease reactivation, time from clinically significant disease reactivation to improvement in BILAG from maximum level (at least an A or B) during the flare was calculated in study days as: date of clinically significant disease reactivation minus (-) date of BILAG improvement. If multiple body systems had a BILAG flare at the visit, then the body system with the most severe score was tracked for improvement; if multiple body systems had the same score (at least an A or B), then just one needed to show improvement.	Baseline (Treatment Randomization) to Week 60
Time From Clinically Significant Disease Reactivation to Recovery to Baseline British Isles Lupus Assessment Group (BILAG) Score or BILAG C	For each participant who experienced disease reactivation, time from clinically significant disease reactivation to recovery to baseline BILAG scores or BILAG C, whichever is worse, was calculated in study days as: date of clinically significant disease reactivation minus (-) date of BILAG recovery.	Baseline (Treatment Randomization) to Week 60
Cumulative Excess Systemic Steroid Dose From Time of Clinically Significant Disease Reactivation to Return to Pre-Flare Dose or End of Trial Participation	For each participant who experienced disease reactivation, excess systemic steroid dose was summed from the time of clinically significant disease reactivation until the dose returns to pre-flare levels or the end of study participation, whichever occurred first. Excess systemic steroid dose was defined as the total dose given for the flare minus (-) a participant's pre-flare steroid dose. Participants who do not have an increase in their steroid use due to the flare had their excess dose set to zero. Steroids include medications that code to a medication class which includes the terms "glucocorticoid" or "corticosteroid". Systemic steroids will include any of these steroids that are taken by mouth (PO), intravenous (IV), or intramuscular (IM).	Baseline (Treatment Randomization) to Week 60
Time From Clinically Significant Disease Reactivation to Return to Pre-Flare Steroid Dose	For each participant who experienced disease reactivation, time from clinically significant disease reactivation to recovery to pre-flare steroid dose was calculated in study days as: date of clinically significant disease reactivation minus (-) date of return to pre-flare steroid dose.	Baseline (Treatment Randomization) to Week 60
Number of Grade 3, 4, or 5 Adverse Events (AEs) Related to Systemic Lupus Erythematosus (SLE)	The number of Grade 3, 4, or 5 AEs classified as possibly, probably, or definitely related to SLE. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.	Baseline (Treatment Randomization) to Week 60
Number of Grade 3, 4, or 5 Adverse Events (AEs) Related to Mycophenolate Mofetil (MMF)	The number of Grade 3, 4, or 5 AEs classified as possibly, probably, or definitely related to MMF. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.	Baseline (Treatment Randomization) to Week 60
Number of Grade 3, 4, or 5 Adverse Events (AEs)	The number of Grade 3, 4, or 5 AEs. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.	Baseline (Treatment Randomization) to Week 60
Number of Serious Adverse Events (SAEs).	The number of SAEs. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.	Baseline (Treatment Randomization) to Week 60
Number of Infection-Related Adverse Events (AEs)	The number of AEs classified as infections. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.	Baseline (Treatment Randomization) to Week 60
Number of Malignancies Reported as Adverse Events (AEs).	The number of malignancies reported as AEs. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.	Baseline (Treatment Randomization) to Week 60
Number of Grade 3, 4, or 5 Hematological Adverse Events (AEs).	The number of Grade 3, 4, or 5 hematological AEs. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.	Baseline (Treatment Randomization) to Week 60
Mortality Related to Systemic Lupus Erythematosus (SLE)	Mortality related to SLE is defined as any death possibly, probably, or definitely related to SLE. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.	Baseline (Treatment Randomization) to Week 60
All-Cause Mortality	All-cause mortality is defined as death from any cause occurring after randomization. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.	Baseline (Treatment Randomization) to Week 60

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Rho Federal Systems Division, Inc.; Autoimmunity Centers of Excellence
• Investigators: Study Chair: Eliza Chakravarty, MD, Oklahoma Medical Research Foundation; Study Chair: Judith A. James, MD, PhD, Oklahoma Medical Research Foundation

Publications and helpful links

General Publications

• Wenderfer SE, Eldin KW. Lupus Nephritis. Pediatr Clin North Am. 2019 Feb;66(1):87-99. doi: 10.1016/j.pcl.2018.08.007.

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Division of Allergy, Immunology, and Transplantation (DAIT) website
• Autoimmunity Centers of Excellence (ACE) website

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 20, 2013
• Primary Completion (ACTUAL): July 3, 2019
• Study Completion (ACTUAL): July 3, 2019

Study Registration Dates

• First Submitted: September 13, 2013
• First Submitted That Met QC Criteria: September 17, 2013
• First Posted (ESTIMATE): September 20, 2013

Study Record Updates

• Last Update Posted (ACTUAL): August 17, 2020
• Last Update Submitted That Met QC Criteria: August 14, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus; Mycophenolate Mofetil (MMF)
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antiprotozoal Agents; Antiparasitic Agents; Antitubercular Agents; Antimalarials; Amebicides; Filaricides; Antinematodal Agents; Anthelmintics; Antibiotics, Antitubercular; Prednisone; Chloroquine; Chloroquine diphosphate; Mycophenolic Acid; Hydroxychloroquine
• Other Study ID Numbers: DAIT ALE06; NIAID CRMS ID#: 20154 (OTHER: DAIT NIAID)