Efficacy and Safety of Sirolimus in Active Systemic Lupus Erythematosus

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2024
• Main ID: NCT04582136
• Date of registration: 03/10/2020
• Prospective Registration: Yes
• Primary sponsor: Chinese SLE Treatment And Research Group
• Public title: Efficacy and Safety of Sirolimus in Active Systemic Lupus Erythematosus SIRIUS
• Scientific title: 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
• Date of first enrolment: March 4, 2021
• Target sample size: 146
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04582136
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

China

Contacts

• Name: Mengtao Li, MD

• Name: Xiaofeng Zeng, MD
• Affiliation: Chinese SLE Treatment and Registration Group

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Drug: Sirolimus

Drug: Placebo

Primary Outcome(s)

The Proportion of Patients Who Achieve an SLE Responder Index-4 (SRI-4) Composite Response at Week 24 [Time Frame: 24 weeks]

Secondary Outcome(s)

Change From Baseline in Physician's Global Assessment of Disease Activity (PGA) Score at Week 24 [Time Frame: 24 weeks]

Change From Baseline in Complement Level at Week 24 [Time Frame: 24 weeks]

Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score at Week 24 [Time Frame: 24 weeks]

Number of Participants With BILAG-based Combined Lupus Assessment (BICLA) Response at Week 24 [Time Frame: 24 weeks]

Change From Baseline in Titers of Anti-dsDNA Antibody at Week 24 [Time Frame: 24 weeks]

Secondary ID(s)

CSTAR_RCT_SLE_001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Beijing Municipal Science & Technology Commission

North China Pharmaceutical Group Corporation