1) Target Disease
a) Subjects with drug-induced SLE, as opposed to idiopathic SLE.
b) Subjects who are renal transplant recipients or candidates.
c) Subjects who are diagnosed as end-stage renal disease.
d) Subjects with persistent non-lupus related pyuria or hematuria (eg, hemorrhagic cystitis).
e) Subjects with a degree of tubulo-interstitial changes that suggests a significant and irreversible decrease in renal function.
2) Medical History and Concurrent Diseases
a) Subjects with autoimmune disease other than SLE as their main diagnosis [eg; Rheumatoid Arthritis (RA), Multiple Sclerosis (MS)].
b) Current symptoms of severe, progressive, or uncontrolled non-SLE related renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, or other concomitant medical conditions that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study.
c) Active CNS lupus (BILAG A or B) with the exception of fatigue or mild stable cognitive dysfunction (screening MRI or other imaging of the brain is not required to rule-out CNS disease in subjects who have no clinical features suggesting active CNS disease).
d) Concomitant illness that in the opinion of the investigator, is likely to require additional moderate to high dose oral corticosteroid therapy (ie, > 10 mg prednisone or prednisone equivalent per day) during the study, (eg; asthma).
e) Female subjects who have evidence of cervical dysplasia that require definitive therapy according to local guidelines or the Consensus Guidelines and have not been definitively treated.
f) Subjects with a history of cancer within the last 5 years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to dosing. Subjects with carcinoma in situ, treated with definitive surgical intervention prior to study entry, are allowed.
g) Subjects with any serious acute bacterial infection (such as pneumonia or pyelonephritis unless treated and complete resolved with antibiotics).
h) Subjects with severe chronic or recurrent bacterial infections (such as recurrent pneumonia, chronic bronchiectasis)
i) Subjects at risk for tuberculosis. Specifically, subjects with:
i) Current clinical, radiographic or laboratory evidence of active or latent TB.
ii) A history of active TB within the last 3 years even if it was treated.
iii) A history of active TB greater than 3 years ago unless there is documentation that the prior anti-TB treatment was appropriate in duration and type.
j) Subjects with herpes zoster that resolved less than 2 months prior to enrollment.
k) Subjects with evidence (as assessed by the Investigator) of active or latent bacterial or viral infections at the time of potential enrollment, including subjects with evidence of Human Immunodeficiency Virus (HIV) infection.
l) Subjects who are impaired, incapacitated, or incapable of completing study related assessments.
3) Physical and Laboratory Test Findings
a) Subjects currently on hydroxychloroquine, chloroquine or quinacrine with retinopathy within 6 months of screening visit. Subjects receiving anti-malarial therapy who are unwilling to follow local standards for routine ophthalmologic follow-up will be excluded.
b) Hepatitis-B surface antigen-positive or Hepatitis B DNA positive subjects.
c) Hepatitis C RNA-positive subjects.
d) Subjects with serum ALT or AST > 3 times upper limit of normal unless in the judgment of the investigator the elevation is explicitly related to SLE.
e) Any other laboratory test results that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study.
4) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for a minimum of 10 weeks (or longer as required by local guidelines) after the dose of study medication.
b) Women who are pregnant or breastfeeding.
c) Women with a positive pregnancy test on enrollment or prior to study drug administration.
d) Males unwilling or unable to follow recommendations for use of contraception specified by the manufacturer of any protocol-permitted disease sparing medication (biologic or non-biologic) being used during the study.
5) Prohibited Therapies and/or Medications
a) Subjects who have at any time in the past received treatment with CTLA4Ig or abatacept for treatment of lupus or lupus nephritis.
b) Subjects not discontinuing azathioprine, leflunomide, methotrexate, cyclophosphamide, belimumab, cyclosporine (or any other calcineurin inhibitor) or any other agents for the treatment of SLE or proteinuria that are not specifically permitted by protocol at least 2 weeks prior to randomization (Day 1).
c) Subjects who have received treatment with any investigational drug within 28 days or within less than 5 terminal half lives of elimination (whichever is longer) of randomization (Day 1).
d) Subjects who have received treatment with rituximab < 6 months prior to the screening visit. (NOTE: subjects who received treatment with rituximab ≥ 6 months prior to the screening visit will be eligible provided their CD 19+ peripheral blood cell count is normal within 2 months of the first dose of study
medication. Subjects not meeting this requirement will be excluded from the study)
e) Subjects who have received therapy with plasmapheresis or lymphapheresis or absorption column within 1 year of screening visit or are scheduled to receive such therapy.
f) Subject who will have need of a live vaccine at any time between enrollment (initiation of screening) within 3 months of discontinuation from the study.
g) Subjects who are scheduled for, or anticipate the need for, non-protocol related surgery (aside from dermatologic procedures and renal biopsies).
h) Subjects in whom MMF treatment is contraindicated or considered inappropriate.
i) Subjects who require dialysis or have been on dialysis within 9 months of the screening visit.
j) Subjects having any transplant surgery requiring maintenance immunosuppressive therapy.
6) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated.
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Eligibility criteria for this study have been carefully considered to ensure the safety of the study subjects and that the results of the study can be used. It is imperative that subjects fully meet all eligibility criteria.