Sirolimus Treatment Of Patients With SLE

Inclusion criteria

• Age > 18;
• Male or female;
• ≥ 4 ACR SLE classification criteria;
• Positive ANA at a titer of ≥ 1/80;
• Stable immunosuppressants (MMF ≤ 3 g/day, azathioprine ≤ 100 mg/day; methotrexate ≤ 15 mg/day) and/or antimalarials (hydroxychloroquine ≤ 400 mg/day) for 30 days prior to screening; stable oral corticosteroids for 2 weeks prior to screening; ≤ 20 mg/day prednisone or equivalent; stable belimumab for 90 days prior to screening;
• BILAG 2004 index (3) level A disease activity in ≥ 1 organ/system except renal or central nervous system or (ii) BILAG 2004 index level B disease activity in ≥ 2 organs/systems if no level A disease activity is present and (iii) SLEDAI ≥ 6;
• Enrollment is approved by adjudication committee.

Exclusion criteria

• Acute SLE flare threatening vital organs;
• Pregnant or lactating;
• Female subjects who are planning to become pregnant during the study or within 3 months after last dosing or male subjects who are considering fathering a child within 3 months after last dosing;
• Abnormal laboratory test results: hemoglobin ≤ 8 g/L (8 g/dL), platelet count ≤ 70 x 109/L (70,000 cells/mm³), white blood cell count ≤ 2.0 x 109/L (2,000 cells/mm³), neutrophils: ≤ 1.5 X 109/L, proteinuria > 3 g/day measured by 24 hour collection or spot urine protein to creatinine ratio of >3;
• Glomerular filtration rate (GFR) < 50 mL/min/1.73 m², any other clinically significant abnormal screening laboratory results as evaluated by the Investigator;
• Moderately serious or serious comorbidities (e.g., diabetes mellitus, congestive heart failure, chronic obstructive pulmonary disease, chronic renal insufficiency) that in investigator's opinion confers high risk for adverse events;
• Patients receiving cyclophosphamide within 3 months;
• Active chronic infections (e.g., HIV, hepatitis B virus, hepatitis C virus, mycobacteria); patients with oral steroid-dependent asthma;
• Infections requiring intravenous antibiotics within a month or oral antibiotics within two weeks of screening;
• Patients taking (unwilling or unable to stop) NAC or other antioxidants within 1 month of screening (which is considered sufficient time to revert GSH to pre-treatment levels;
• Patients receiving rituximab within 12 months or other biologic therapy within five half lives;
• Patients receiving mTOR inhibitors (rapamycin/sirolimus, everolimus);
• Patients enrolled in other interventional trials.