Efficacy and Safety of Sirolimus in Active Systemic Lupus Erythematosus

Prior treatment

• Concomitant connective tissue disease or inflammatory disease that might confound efficacy assessments, e.g., systemic sclerosis, rheumatoid arthritis, dermatomyositis/polymyositis, etc;
• Previous treatment with sirolimus or allergic to sirolimus;
• Calcineurin inhibitors (e.g., tacrolimus or cyclosporin A) within 1 month;
• Concurrent active or uncontrolled infection (such as tuberculosis and hepatitis) requiring antibiotics or antivirus;
• Major surgery within the past month;
• Previous stem cell transplantation (including hematopoietic stem cell transplantation and mesenchymal stem cell transplantation);

Other illness

• Any condition that may require multiple courses of systemic corticosteroids (e.g., uncontrolled asthma, COPD);
• Suffering from malignant tumors or a history of malignant tumors within 5 years before screening, or a history of lymphoproliferative diseases: Patients with previously treated cutaneous squamous cell carcinoma and basal cell carcinoma without evidence of recurrence are allowed to enroll; and Patients with cervical cancer in situ who have documented formal surgical cure are allowed to enroll;
• Have a history of splenectomy;
• Subjects has certain conditions that may lead to dropping out of the study in advance or that may bring risk to subjects themselves if they participate in the study. This is judged by experienced clinicians.

Lab values

• Severe active lupus nephritis (urinary protein ≥3.5g/24h or urine protein/creatine ration\> 3500mg/g or eGFR \< 60ml/1.73m2/min);
• WBC count \<3×10\^9/L;
• Abnormal biochemical indices including: alanine transaminase (ALT) or aspartate aminotransferase (AST) \>1.5 times upper limit of laboratory reference range; total bilirubin or blood lipid (including total cholesterol, triglycerides, and low-density lipoprotein) \>2 times upper limit of laboratory reference range;

Other

• Neuropsychiatric SLE;
• Pregnant or breast-feeding women;
• Intravenous CTX within 6 months of enrollment;
• Intravenous immunoglobulin or prednisone dose \>100mg/day within 3 months;
• Traditional Chinese Herb (such as Tripterygium wilfordii Hook F) within 1 month;

• Age between 18\~65 years;
• Fulfilling the 2012 SLICC criteria for SLE; time from SLE diagnosis ≥ 3 months;
• Active disease as defined by a SLEDAI-2K score of ≥4 (not including scores for anti-dsDNA antibody and hypocomplementemia) at screening;
• Serologically active defining as positive anti-dsDNA antibody (\>10IU/ml) or hypocomplementemia (C3\<0.90g/L)
• Before the first dose of sirolimus, a stable regimen of oral corticoids (0-20 mg/day, prednisone or equivalent) ≥4 weeks; doses of antimalarials, or immunosuppressive agents (mycophenolate mofetil \[MMF\]/mycophenolic acid \[MPA\] ≤1.5g/day, or MTX ≤15mg/week) are required to be stable for at least 12 weeks prior to first dose). In addition, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, NSAIDs or other analgesics should be stable for at least 2 weeks.