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Key inclusion & exclusion criteria
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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.
Age minimum:
18 Years
Age maximum:
70 Years
Gender:
All
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Secondary Outcome(s)
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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]
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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]
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Number of Grade 3, 4, or 5 Hematological Adverse Events (AEs).
[Time Frame: Baseline (Treatment Randomization) to Week 60]
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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]
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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]
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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]
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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]
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Number of Grade 3, 4, or 5 Adverse Events (AEs) Related to Systemic Lupus Erythematosus (SLE)
[Time Frame: Baseline (Treatment Randomization) to Week 60]
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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]
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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]
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Time to Clinically Significant Disease Reactivation
[Time Frame: Baseline (Treatment Randomization) to Week 60]
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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]
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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]
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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]
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All-Cause Mortality
[Time Frame: Baseline (Treatment Randomization) to Week 60]
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Number of Malignancies Reported as Adverse Events (AEs).
[Time Frame: Baseline (Treatment Randomization) to Week 60]
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Number of Serious Adverse Events (SAEs).
[Time Frame: Baseline (Treatment Randomization) to Week 60]
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Time From Clinically Significant Disease Reactivation to Return to Pre-Flare Steroid Dose
[Time Frame: Baseline (Treatment Randomization) to Week 60]
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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]
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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]
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Mortality Related to Systemic Lupus Erythematosus (SLE)
[Time Frame: Baseline (Treatment Randomization) to Week 60]
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Number of Grade 3, 4, or 5 Adverse Events (AEs)
[Time Frame: Baseline (Treatment Randomization) to Week 60]
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Change From Baseline in the Lupus Quality of Life (QoL)Score
[Time Frame: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60]
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Cumulative Systemic Steroid Dose by Week 60
[Time Frame: Baseline (Treatment Randomization) to Week 60]
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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]
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Number of Grade 3, 4, or 5 Adverse Events (AEs) Related to Mycophenolate Mofetil (MMF)
[Time Frame: Baseline (Treatment Randomization) to Week 60]
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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]
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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]
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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]
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Number of Participants Experiencing Any British Isles Lupus Assessment Group (BILAG) A Flare by Week 60
[Time Frame: Baseline (Treatment Randomization) to Week 60]
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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]
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Number of Infection-Related Adverse Events (AEs)
[Time Frame: Baseline (Treatment Randomization) to Week 60]
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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]
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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]
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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]
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