Randomized MMF Withdrawal in Systemic Lupus Erythematosus (SLE)
Condition: Systemic Lupus Erythematosus; SLE
MeSH terms: Lupus Erythematosus, Systemic
Intervention: Mycophenolate Mofetil; Hydroxychloroquine or Chloroquine; Prednisone
Intervention description: 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.; 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; 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.
Intervention MeSH terms: Mycophenolic Acid; Hydroxychloroquine; Chloroquine; Chloroquine diphosphate; Prednisone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Systemic Lupus Erythematosus; Mycophenolate Mofetil (MMF)

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.
    

Eligibility criteria:

        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.