Efficacy and Safety of Sirolimus in Active Systemic Lupus Erythematosus

• Status: Not yet recruiting
• Trial end date: 2022-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a multi-center, double-blinded, randomized, placebo-controlled, phase 2 study to evaluate the efficacy and safety of sirolimus administered in addition to standard therapy, in patients with active SLE disease.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Chinese SLE Treatment And Research Group
• Collaborators: Beijing Municipal Science & Technology Commission; North China Pharmaceutical Group Corporation
• Treatments: Sirolimus

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Concomitant connective tissue disease or inflammatory disease that might confound efficacy assessments, e.g., systemic sclerosis, rheumatoid arthritis, dermatomyositis/polymyositis, etc;

• Neuropsychiatric SLE;

• Severe active lupus nephritis (urinary protein ≥3.5g/24h or urine protein/creatine ration> 3500mg/g or eGFR < 60ml/1.73m2/min);

• Pregnant or breast-feeding women;

• Previous treatment with sirolimus or allergic to sirolimus;

• Intravenous CTX within 6 months of enrollment;

• Intravenous immunoglobulin or prednisone dose >100mg/day within 3 months;

• Calcineurin inhibitors (e.g., tacrolimus or cyclosporin A) within 1 month;

• Traditional Chinese Herb (such as Tripterygium wilfordii Hook F) within 1 month;

• Concurrent active or uncontrolled infection (such as tuberculosis and hepatitis) requiring antibiotics or antivirus;

• 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;

• 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.