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Trial record 1 of 1 for:    ALE06
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Randomized MMF Withdrawal in Systemic Lupus Erythematosus (SLE) (ALE06)

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ClinicalTrials.gov Identifier: NCT01946880
Recruitment Status : Terminated (Slow enrollment.)
First Posted : September 20, 2013
Results First Posted : August 17, 2020
Last Update Posted : August 17, 2020
Sponsor:
Collaborators:
Autoimmunity Centers of Excellence
Rho Federal Systems Division, Inc.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE September 13, 2013
First Posted Date  ICMJE September 20, 2013
Results First Submitted Date  ICMJE July 3, 2020
Results First Posted Date  ICMJE August 17, 2020
Last Update Posted Date August 17, 2020
Actual Study Start Date  ICMJE November 20, 2013
Actual Primary Completion Date July 3, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 14, 2020)
Number of Participants Experiencing Clinically Significant Disease Reactivation by Week 60 [ Time Frame: Baseline (Treatment Randomization) to 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
Original Primary Outcome Measures  ICMJE
 (submitted: September 17, 2013)
The proportion of subjects in each arm experiencing clinically significant disease reactivation. [ Time Frame: Week 60 ]
Clinically significant SLE reactivation requires both:
  1. A SELENA-SLEDAI*-defined mild/moderate or severe flare and
  2. Increased immunosuppressive therapy on a sustained basis
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2020)
  • Time to Clinically Significant Disease Reactivation [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • 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 [ Time Frame: Baseline (Treatment Randomization) to 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.
  • 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 [ Time Frame: Baseline (Treatment Randomization) to 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.
  • 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 [ Time Frame: Baseline (Treatment Randomization) to 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.
  • 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 [ Time Frame: Baseline (Treatment Randomization) to 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. MMF: mycophenolate mofetil
  • 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 [ Time Frame: Baseline (Treatment Randomization) to 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. MMF: mycophenolate mofetil
  • 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 [ Time Frame: Baseline (Treatment Randomization) to 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.
  • 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 [ Time Frame: Baseline (Treatment Randomization) to 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.
  • 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 [ Time Frame: Baseline (Treatment Randomization) to 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.
  • 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 [ Time Frame: Baseline (Treatment Randomization) to 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. MMF: mycophenolate mofetil
  • 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 [ Time Frame: Baseline (Treatment Randomization) to 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. MMF: mycophenolate mofetil
  • Time to First Mild/Moderate or Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • Time to First Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • Number of Participants Experiencing Any British Isles Lupus Assessment Group (BILAG) A Flare by Week 60 [ Time Frame: Baseline (Treatment Randomization) to 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.
  • Number of Participants in the Lupus Nephritis Subgroup Experiencing a British Isles Lupus Assessment Group (BILAG) A Renal Flare by Week 60 [ Time Frame: Baseline (Treatment Randomization) to 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.
  • 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 [ Time Frame: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60 ]
    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.
  • The Addition of Aggressive Adjunctive Therapy to Mycophenolate Mofetil (MMF) or Change in MMF Therapy to Cytotoxic Drug Due to Flare by Week 60 [ Time Frame: Baseline (Treatment Randomization) to 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.
  • Cumulative Systemic Steroid Dose by Week 60 [ Time Frame: Baseline (Treatment Randomization) to 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.
  • Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT-F) Fatigue Scale (FS): Total Score [ Time Frame: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60 ]
    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.
  • Change From Baseline in the Short Form Health Survey (SF-36) Physical Functioning (PF) Score [ Time Frame: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60 ]
    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.
  • Change From Baseline in the Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score [ Time Frame: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60 ]
    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.
  • Change From Baseline in the Lupus Quality of Life (QoL)Score [ Time Frame: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60 ]
    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.
  • Time From Clinically Significant Disease Reactivation to Improvement in British Isles Lupus Assessment Group (BILAG) From Maximum Level During Flare [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • Time From Clinically Significant Disease Reactivation to Recovery to Baseline British Isles Lupus Assessment Group (BILAG) Score or BILAG C [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • Cumulative Excess Systemic Steroid Dose From Time of Clinically Significant Disease Reactivation to Return to Pre-Flare Dose or End of Trial Participation [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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).
  • Time From Clinically Significant Disease Reactivation to Return to Pre-Flare Steroid Dose [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • Number of Grade 3, 4, or 5 Adverse Events (AEs) Related to Systemic Lupus Erythematosus (SLE) [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • Number of Grade 3, 4, or 5 Adverse Events (AEs) Related to Mycophenolate Mofetil (MMF) [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • Number of Grade 3, 4, or 5 Adverse Events (AEs) [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • Number of Serious Adverse Events (SAEs). [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • Number of Infection-Related Adverse Events (AEs) [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • Number of Malignancies Reported as Adverse Events (AEs). [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • Number of Grade 3, 4, or 5 Hematological Adverse Events (AEs). [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • Mortality Related to Systemic Lupus Erythematosus (SLE) [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
  • All-Cause Mortality [ Time Frame: Baseline (Treatment Randomization) to Week 60 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2013)
  • Time to Clinically Significant Disease Reactivation [ Time Frame: Up to week 60 ]
  • Aggregate of proportion of subjects with any SELENA-SLEDAI flare and proportion of subjects with any severe SELENA-SLEDAI* flare [ Time Frame: Week 60 ]
    Defined by disease manifestation (renal disease / extra-renal disease) and by baseline MMF dosing group (≤ 2000 mg per day / > 2000 mg per day).
  • Time from initiation of withdrawal to first SELENA-SLEDAI* flare and time to first severe SELENA-SLEDAI* flare [ Time Frame: Up to Week 60 ]
  • Proportion of subjects with any BILAG A flare [ Time Frame: Week 60 ]
  • Proportion of subjects in the renal subgroup with BILAG* Renal A flare [ Time Frame: Week 60 ]
  • Change in SLICC/DI [ Time Frame: Baseline to Week 24 ]
  • Change in SLICC/DI [ Time Frame: Baseline to Week 48 ]
  • Change in SLICC/DI [ Time Frame: Baseline to Week 60 ]
  • Proportion of subjects with aggressive adjunctive therapy added to MMF [ Time Frame: Week 60 ]
    Proportion of subjects with aggressive adjunctive therapy added to MMF (including IV immunoglobulin or rituximab) or change in MMF therapy to cytotoxic drug (e.g., cyclophosphamide) due to flare.
  • Cumulative systemic steroid dose [ Time Frame: Week 60 ]
  • Change in FACIT fatigue score [ Time Frame: Baseline to Week 24 ]
  • Change in FACIT fatigue score [ Time Frame: Baseline to Week 48 ]
  • Change in FACIT fatigue score [ Time Frame: Baseline to Week 60 ]
  • Change in Lupus QoL-US [ Time Frame: Baseline to Week 24 ]
  • Change in Lupus QoL-US [ Time Frame: Baseline to Week 48 ]
  • Change in Lupus QoL-US [ Time Frame: Baseline to Week 60 ]
  • Time to improvement in BILAG from maximum level during flare [ Time Frame: Maximum BILAG score during clinically significant disease reactivation to BILAG improvement up to week 60 ]
  • Time to recovery of baseline BILAG scores [ Time Frame: Clinically significant disease reactivation to recovery of baseline BILAG scores or BILAG C, whichever is worse, up to week 60 ]
  • Cumulative excess systemic steroid dose [ Time Frame: From time of clinically significant disease reactivation to return to pre-flare dose or week 60 ]
  • Time to return to pre-flare steroid dose [ Time Frame: clinically significant disease reactivation (flare) to pre-flare steroid dose or week 60 ]
  • Amount of SLE Related Grade 3-5 adverse events [ Time Frame: Up to Week 60 ]
    As defined by the National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) system, which are defined as possibly, probably, or definitely related to SLE.
  • Amount of MMF related Grade 3-5 adverse events [ Time Frame: Up to Week 60 ]
    As defined by the NCI-CTCAE system, which are defined as possibly, probably, or definitely related to MMF.
  • Amount of all NCI-CTCAE Grade 3-5 adverse events. [ Time Frame: Up to Week 60 ]
  • Amount of serious adverse events. [ Time Frame: Up to Week 60 ]
  • Frequency of malignancies [ Time Frame: Up to Week 60 ]
  • Amount of NCI-CTCAE Grade 3-5 hematological events. [ Time Frame: Up to Week 60 ]
  • Total incidence of mortality possibly, probably, or definitely related to SLE. [ Time Frame: Up to Week 60 ]
  • Total incidence of all-cause mortality [ Time Frame: Up to Week 60 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Randomized MMF Withdrawal in Systemic Lupus Erythematosus (SLE)
Official Title  ICMJE An Investigator-Initiated, Phase II, Randomized, Withdrawal Study of Mycophenolate Mofetil (MMF) in Patients With Stable, Quiescent Systemic Lupus Erythematosus (SLE)
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Systemic Lupus Erythematosus
  • SLE
Intervention  ICMJE
  • 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 Name: 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 Name: corticosteroid
Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: Mycophenolate Mofetil
    • Drug: Hydroxychloroquine or Chloroquine
    • Drug: Prednisone
  • 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).
    Interventions:
    • Drug: Mycophenolate Mofetil
    • Drug: Hydroxychloroquine or Chloroquine
    • Drug: Prednisone
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. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 15, 2018)
102
Original Estimated Enrollment  ICMJE
 (submitted: September 17, 2013)
120
Actual Study Completion Date  ICMJE July 3, 2019
Actual Primary Completion Date July 3, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01946880
Other Study ID Numbers  ICMJE DAIT ALE06
NIAID CRMS ID#: 20154 ( Other Identifier: DAIT NIAID )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE
  • Autoimmunity Centers of Excellence
  • Rho Federal Systems Division, Inc.
Investigators  ICMJE
Study Chair: Eliza Chakravarty, MD Oklahoma Medical Research Foundation
Study Chair: Judith A. James, MD, PhD Oklahoma Medical Research Foundation
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP