Efficacy and Safety of Sirolimus in Active Systemic Lupus Erythematosus

NCT04582136 | Active Not Recruiting Phase 3

• 1 other identifier: CSTAR_RCT_SLE_001
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 6

Brief Summary

This is a multi-center, double-blinded, randomized, placebo-controlled, phase 3 study to evaluate the efficacy and safety of sirolimus administered in addition to standard therapy, in patients with active SLE disease.

Conditions

Systemic Lupus Erythematosus

Keywords

mTOR; systemic lupus erythematosus; SLE; lupus erythematosus; sirolimus; rapamycin

Outcome Measures

Primary Outcomes (1)

• The Proportion of Patients Who Achieve an SLE Responder Index-4 (SRI-4) Composite Response at Week 24

  SLE responder index-4 (SRI-4), is a composite outcome includes all of the following outcomes: a reduction of SLEDAI-2K ≥ 4 points, no new BILAG A organ domain scores and no more than 1 new BILAG B organ domain scores, and no worsening of PGA (increase \< 0.3).

  24 weeks

Secondary Outcomes (5)

• Change From Baseline in Complement Level at Week 24

  24 weeks

• Change From Baseline in Titers of Anti-dsDNA Antibody at Week 24

  24 weeks

• Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score at Week 24

  24 weeks

• Change From Baseline in Physician's Global Assessment of Disease Activity (PGA) Score at Week 24

  24 weeks

• Number of Participants With BILAG-based Combined Lupus Assessment (BICLA) Response at Week 24

  24 weeks

Other Outcomes (12)

• Change From Baseline in SLE Disease Activity Score (SLE-DAS) at Week 24

  24 weeks

• Percentage of Patients With Clinical Remission at week 24

  24 weeks

• Percentage of Patients With Lupus Low Disease Activity State (LLDAS) at week 24

  24 weeks

Study Arms (2)

Sirolimus plus SOC

EXPERIMENTAL

Sirolimus plus standard therapy (SOC) for SLE; Generic name: sirolimus (0.5mg capsule); Dosage: 1.5mg/day; Administration route: Oral

Drug: Sirolimus

Placebo plus SOC

PLACEBO COMPARATOR

Placebo plus standard therapy (SOC) for SLE; Drug: Placebo comparator plus SOC; Administration route: Oral

Drug: Placebo

Interventions

Sirolimus DRUG

In the double-blinded phase, sirolimus 1.5mg/day plus SOC is administered throughout 24 weeks; in the open-label extension period, patients who opt to participate continue on sirolimus 1.5mg/day plus SOC for an additional 24 weeks.

Also known as: rapamycin

Sirolimus plus SOC

Placebo DRUG

In the double-blinded phase, placebo plus SOC is administered throughout 24 weeks; in the open-label extension period, patients who opt to participate are switched to receive sirolimus 1.5mg/day plus SOC for an additional 24 weeks.

Placebo plus SOC

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Chinese SLE Treatment And Research Group: lead
• Beijing Municipal Science & Technology Commission: collaborator
• North China Pharmaceutical Group Corporation: collaborator

Study Sites (6)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100053, China

Location

Shenzhen People's Hospital

Shenzhen, Guangdong, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Location

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Location

The First Hospital of China Medical University

Shenyang, Liaoning, China

Location

First Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, China

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Xiaofeng Zeng, MD

  Chinese SLE Treatment and Registration Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Rheumatology and Immunology Department Chinese Academy of Medical Sciences &Peking Union Medical College Hospital

Study Record Dates

• First Submitted: October 3, 2020
• First Posted: October 9, 2020
• Study Start: March 4, 2021
• Primary Completion: April 21, 2025
• Study Completion: January 1, 2026
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: IPD will be available when the study result is published.

Locations

CN (6)