Evaluating sirolimus for treating active systemic lupus erythematosus

Efficacy and Safety of Sirolimus in Patients With Active Systemic Lupus Erythematosus Despite Standard of Care: a Multi-center, Double Blinded, Randomized, Placebo-controlled, Phase 2 Trial

This study is testing if sirolimus can help people with active lupus feel better while they are already on standard treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 146 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Chinese SLE Treatment And Research Group (Academic / other)
• Drugs / interventions: prednisone
• Locations: 6 sites (Beijing, Beijing and 5 other locations)
• Trial ID: NCT04582136 on ClinicalTrials.gov

What this trial studies

This clinical trial is a multi-center, double-blinded, randomized, placebo-controlled phase 2 study aimed at assessing the efficacy and safety of sirolimus in patients with active systemic lupus erythematosus (SLE) who are already receiving standard therapy. Participants aged 18 to 65 with a specific disease activity score will be randomly assigned to receive either sirolimus or a placebo for 24 weeks, followed by an open-label extension phase where all participants will receive sirolimus. The study will take place across six major rheumatological centers in China.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 65 with active systemic lupus erythematosus and specific serological markers despite receiving conventional treatment.

Not a fit: Patients with concomitant connective tissue diseases or those who do not meet the specific disease activity criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with active systemic lupus erythematosus who do not respond adequately to standard therapies.

How similar studies have performed: While this approach is being evaluated in this trial, similar studies using mTOR inhibitors in autoimmune diseases have shown promise, suggesting potential for success.

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.

Where this trial is running

Beijing, Beijing and 5 other locations

• Peking Union Medical College Hospital — Beijing, Beijing, China (Recruiting)
• Shenzhen People's Hospital — Shenzhen, Guangdong, China (Recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Recruiting)
• The Second Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Recruiting)
• The First Hospital of China Medical University — Shenyang, Liaoning, China (Recruiting)
• First Affiliated Hospital of Kunming Medical University — Kunming, Yunnan, China (Recruiting)

Study contacts

• Principal investigator: Xiaofeng Zeng, MD — Chinese SLE Treatment and Registration Group
• Study coordinator: Mengtao Li, MD

Conditions Systemic Lupus Erythematosus; mTOR; systemic lupus erythematosus; SLE; lupus erythematosus; sirolimus; rapamycin