AzTrials
AzTrials

Systemic Lupus ErythematosusPhase 2ALE06NCT01946880

Randomized MMF Withdrawal in Systemic Lupus Erythematosus (SLE)

A Phase 2 study testing Mycophenolate Mofetil, Hydroxychloroquine or Chloroquine and Prednisone in people with Systemic Lupus Erythematosus and SLE, run by National Institute of Allergy and Infectious Diseases (NIAID) at 19 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Systemic Lupus Erythematosus, SLE
What is being tested?
Mycophenolate Mofetil, Hydroxychloroquine or Chloroquine and Prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
102 participants
Where
19 sitesUnited States
Study dates
20 Nov 2013to 3 Jul 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Able and willing to give written informed consent and comply with requirements of the study;
  • Age 18 - 70 years, inclusive, at randomization;
  • Diagnosis of SLE, per the American College of Rheumatology (ACR) criteria;
  • m-SLEDAI score < 4 at screening visit (SLEDAI score without serologies);
  • Physician Global Assessment (0-3) score of 1 or less at screening visit;
  • On a stable dose of MMF (1000-3000 mg/day) for at least 12 weeks prior to randomization;
Show all 14Show fewer
  • 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.
  • 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).
  • 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;
  • On maintenance HCQ or chloroquine at a stable dose for at least 12 weeks prior to randomization.

Who cannot join

  • A history of life-threatening neuropsychiatric SLE within 1 calendar year prior to randomization;
  • 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;
Show all 27Show fewer
  • 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).
  • Prednisone > 25 mg/day (or its equivalent) within 24 weeks prior to randomization for lupus activity;
  • 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;
  • Plasmapheresis or IV immunoglobulin within 12 weeks prior to randomization;
  • Cyclophosphamide therapy within 24 weeks prior to randomization;
  • Concomitant therapy with belimumab within 24 weeks prior to randomization;
  • B cell depleting therapy within two calendar years of randomization;
  • Experimental therapy within the 24 weeks, or five half-lives of the agent, whichever is longer, prior to randomization;
  • Solid organ or stem cell transplantation;
  • 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.
  • 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;
  • 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.
  • 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;
  • Pregnant or lactating, or intention to pursue pregnancy within three months after the completion of the study;
  • 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).
  • Drug or alcohol abuse within one calendar year of randomization;
  • Other medical or psychiatric conditions that the investigator feels would place the subject at special risk by participation in this protocol.

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University

    Atlanta, Georgia, 30303

  • Brigham & Women's Hospital

    Boston, Massachusetts, 02115

  • Medical University of South Carolina

    Charleston, South Carolina, 29412

  • University of Chicago

    Chicago, Illinois, 60637-1426

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • University of Colorado

    Denver, Colorado, 80204

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Penn State University

    Hershey, Pennsylvania, 17033

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Feinstein Institute for Medical Research

    Manhasset, New York, 11025

  • University of Miami Hospitals and Clinics

    Miami, Florida, 33136

  • New York University, Langone Medical Center

    New York, New York, 10016

  • Weill Cornell Medical College: Hospital for Special Surgery - Rheumatology Division

    New York, New York, 10021

  • Oklahoma Medical Research Foundation

    Oklahoma City, Oklahoma, 73104

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • UCSD

    San Diego, California, 92093-0943

  • UCSF School of Medicine

    San Francisco, California, 94143-0633

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Mycophenolate Mofetil, Hydroxychloroquine or Chloroquine, Prednisone
Keywords
Systemic Lupus Erythematosus, Mycophenolate Mofetil (MMF)
Medical subject headings
Lupus Erythematosus, Systemic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mycophenolate MofetilDrug

    Also called MMF

    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.

  • Hydroxychloroquine or ChloroquineDrug

    Also called Plaquenil®, Chloroquine Phosphate®

    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

  • PrednisoneDrug

    Also called corticosteroid

    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.

Study groups in NCT01946880
Study groupRoleWhat they receive
Mycophenolate Mofetil WithdrawalExperimentalThese 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).
Receives: Drug: Mycophenolate Mofetil; Drug: Hydroxychloroquine or Chloroquine; Drug: Prednisone
Mycophenolate Mofetil MaintenanceActive comparatorThese subjects will continue MMF treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Receives: Drug: Mycophenolate Mofetil; Drug: Hydroxychloroquine or Chloroquine; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Baseline (Treatment Randomization) to Week 60

Secondary outcomes (35)

  1. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  2. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  3. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  4. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  5. 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

    Measured: Baseline (Treatment Randomization) to Week 60

  6. 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

    Measured: Baseline (Treatment Randomization) to Week 60

  7. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  8. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  9. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  10. 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

    Measured: Baseline (Treatment Randomization) to Week 60

  11. 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

    Measured: Baseline (Treatment Randomization) to Week 60

  12. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  13. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  14. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  15. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  16. 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.

    Measured: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60

  17. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  18. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  19. 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.

    Measured: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60

  20. 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.

    Measured: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60

  21. 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.

    Measured: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60

  22. 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.

    Measured: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60

  23. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  24. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  25. 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).

    Measured: Baseline (Treatment Randomization) to Week 60

  26. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  27. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  28. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  29. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  30. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  31. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  32. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  33. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  34. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

  35. 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.

    Measured: Baseline (Treatment Randomization) to Week 60

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2013 (estimated)
  2. Study start20 Nov 2013
  3. Primary completion3 Jul 2019
  4. Study completion3 Jul 2019

Why it stopped: Slow enrollment.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
102 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01946880
Sponsor's protocol ID
DAIT ALE06
Other IDs
NIAID CRMS ID#: 20154
Acronym
ALE06
Status last verified
Aug 2020
First submitted
13 Sep 2013
Last updated
17 Aug 2020
Data monitoring committee
Yes

Publications

  • Chakravarty EF, Utset T, Kamen DL, Contreras G, McCune WJ, Aranow C, Kalunian K, Massarotti E, Clowse MEB, Rovin BH, Lim SS, Majithia V, Dall'Era M, Looney RJ, Erkan D, Saxena A, Olsen NJ, Ko K, Guthridge JM, Goldmuntz E, Springer J, D'Aveta C, Keyes-Elstein L, Barry B, Pinckney A, McNamara J, James JA. Mycophenolate mofetil withdrawal in patients with systemic lupus erythematosus: a multicentre, open-label, randomised controlled trial. Lancet Rheumatol. 2024 Mar;6(3):e168-e177. doi: 10.1016/S2665-9913(23)00320-X. Epub 2024 Jan 29.

    PubMed 38301682

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

    PubMed 30454753

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Mycophenolate Mofetil, Hydroxychloroquine or Chloroquine and Prednisone in people with Systemic Lupus Erythematosus and SLE, run by National Institute of Allergy and Infectious Diseases (NIAID) at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing Clinically Significant Disease Reactivation by Week 60 (time frame: Baseline (Treatment Randomization) to Week 60). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01946880, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in