Efficacy and Safety of Sirolimus in Active Systemic Lupus Erythematosus

Launched by CHINESE SLE TREATMENT AND RESEARCH GROUP · Oct 3, 2020

Keywords

ClinConnect Summary

This clinical trial is investigating the effectiveness and safety of a medication called sirolimus for patients with active systemic lupus erythematosus (SLE), a condition that causes the immune system to attack the body’s own tissues. The study is designed to see if adding sirolimus to the usual treatments helps improve symptoms for people who are already on stable doses of other medications. The trial is taking place at multiple locations and is currently looking for participants aged 18 to 65 who meet specific criteria, such as having a recent diagnosis of SLE and showing signs of active disease.

Eligible participants will need to have been stable on their current medications for a certain period before starting the trial. They will be randomly assigned to receive either sirolimus or a placebo (a non-active treatment) without knowing which one they are getting. Throughout the study, participants will be closely monitored for any side effects and changes in their condition. It's important to note that some individuals may not qualify for the trial if they have certain other health issues or have recently received specific treatments. Overall, this trial aims to provide more information about sirolimus and how it might help those living with systemic lupus erythematosus.

Gender

ALL

Eligibility 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;
• • Any condition that may require multiple courses of systemic corticosteroids (e.g., uncontrolled asthma, COPD);
• • Major surgery within the past month;
• • 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;
• • Previous stem cell transplantation (including hematopoietic stem cell transplantation and mesenchymal stem cell transplantation);
• • 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.