Systemic Lupus ErythematosusPhase 3SIRIUSNCT04582136
Efficacy and Safety of Sirolimus in Active Systemic Lupus Erythematosus
A Phase 3 study testing Sirolimus in people with Systemic Lupus Erythematosus, run by Chinese SLE Treatment And Research Group at 6 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 146 participants
- Where
- 6 sitesChina
- Study dates
- 4 Mar 2021to Jan 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
China6 sites
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100053
First Affiliated Hospital of Kunming Medical University
Kunming, Yunnan
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi
The First Hospital of China Medical University
Shenyang, Liaoning
Shenzhen People's Hospital
Shenzhen, Guangdong
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan
About this study
Official 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 3 Trial
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.
Read the detailed description
This study is a multi-center, double-blinded, randomized, placebo-controlled, phase 3 clinical trial to assess the efficacy and safety of sirolimus in patients with active systemic lupus erythematosus despite receiving standard background therapy.
Six large rheumatological referring centers across from China will participate in the study.
The study is divided into two phases. The first phase is a 24-week randomized, double-blinded, placebo-controlled trial, from which the primary end point will be generated, and the second phase is a 24-week open-labeled extension trial.
The study enrolls SLE patients between 18~65 years old who have SLEDAI-2K score ≥4 (not including scores for anti-dsDNA antibody and hypocomplementemia), despite conventional treatment (e.g., immunosuppressants, antimalarial drugs, glucocorticoids, NSAIDs, anti-hypertensive drugs, and/or topical medications). In addition, subjects must be serologically active (positive anti-dsDNA antibody and/or hypocomplementemia).
Subjects will be randomly assigned by 1:1 ratio to receive sirolimus (1.5mg/day) or placebo for the first 24-week phase. In the second 24-week open-labeled phase, sirolimus patients receive the same dose of sirolimus, and placebo group are switched to receive sirolimus at 1.5mg/day
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- Sirolimus, Placebo
- Keywords
- mTOR, systemic lupus erythematosus, SLE, lupus erythematosus, sirolimus, rapamycin
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called rapamycin
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus plus SOC | Experimental | Sirolimus plus standard therapy (SOC) for SLE; Generic name: sirolimus (0.5mg capsule); Dosage: 1.5mg/day; Administration route: Oral Receives: Drug: Sirolimus |
| Placebo plus SOC | Placebo comparator | Placebo plus standard therapy (SOC) for SLE; Drug: Placebo comparator plus SOC; Administration route: Oral Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 24 weeks
Secondary outcomes (5)
Change From Baseline in Complement Level at Week 24
Serum complement refers to C3 and C4, which are both detected in the central lab.
Measured: 24 weeks
Change From Baseline in Titers of Anti-dsDNA Antibody at Week 24
Anti-dsDNA antibody is detected in the central lab using chemiluminescence.
Measured: 24 weeks
Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score at Week 24
The SLEDAI-2K is an established, validated SLE activity index. It is based on the presence of 24 features in 9 organ systems and measures disease activity in SLE patients in the previous 30 days. It is weighted according to the feature. Features are scored by the assessing physician if present within the last 30 days with more severe features having higher scores, and then simply added to determine the total SLEDAI 2K score, which ranges from 0 to 105, with higher scores representing increased disease activity.
Measured: 24 weeks
Change From Baseline in Physician's Global Assessment of Disease Activity (PGA) Score at Week 24
PGA is recorded on a visual analogue scale (VAS; 0.0 to 10.0 centimeter [cm]). The scale for the physician's assessment ranges for 'no lupus activity' (0.0) to 'extremely active lupus' (10.0).
Measured: 24 weeks
Number of Participants With BILAG-based Combined Lupus Assessment (BICLA) Response at Week 24
BICLA response defined as participants meeting following criteria: 1. BILAG improvement (all BILAG A scores at baseline improved to either B, C or D and all BILAG B scores at baseline improved to C or D and no worsening in disease activity defined as no new BILAG A scores and <= 1 new BILAG B score) and 2. no worsening of total SLEDAI-2K from baseline 3. < 1 cm increase in PGA and 4. no treatment failure criteria met. BILAG: assesses disease extent, severity (range: A [severe] to E [no disease]). SLEDAI-2K: assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). PGA: assesses worsening in participant's general health status (0.0= 'no lupus activity' to 10.0 = 'extremely active lupus').
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2020
- Study start4 Mar 2021
- Primary completion21 Apr 2025
- Study completionJan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 146 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese SLE Treatment And Research Group
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing Municipal Science & Technology Commission, North China Pharmaceutical Group Corporation
- Responsible party
- Principal investigator, Xiaofeng Zeng, Chinese SLE Treatment And Research Group
- Investigators
- Xiaofeng Zeng, MD, Principal investigator, Chinese SLE Treatment and Registration Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04582136
- Sponsor's protocol ID
- CSTAR_RCT_SLE_001
- Acronym
- SIRIUS
- Status last verified
- Sep 2025
- First submitted
- 3 Oct 2020
- Last updated
- 26 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all IPD that underlie results in a publication
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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 3 Trial
- ClinicalTrials.gov ID
- NCT04582136
- Acronym / sponsor ID
- SIRIUS / CSTAR_RCT_SLE_001
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- mTOR, systemic lupus erythematosus, SLE, lupus erythematosus, sirolimus, rapamycin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 146 participants (estimated)
- Lead sponsor
- Chinese SLE Treatment And Research GroupUniversity, hospital or other
- Collaborators
- Beijing Municipal Science & Technology Commission, North China Pharmaceutical Group Corporation
- Study start
- 4 Mar 2021 (actual)
- Primary completion
- 21 Apr 2025 (actual)
- Study completion
- Jan 2026 (estimated)
- First posted
- 9 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study is a multi-center, double-blinded, randomized, placebo-controlled, phase 3 clinical trial to assess the efficacy and safety of sirolimus in patients with active systemic lupus erythematosus despite receiving standard background therapy.
Six large rheumatological referring centers across from China will participate in the study.
The study is divided into two phases. The first phase is a 24-week randomized, double-blinded, placebo-controlled trial, from which the primary end point will be generated, and the second phase is a 24-week open-labeled extension trial.
The study enrolls SLE patients between 18~65 years old who have SLEDAI-2K score ≥4 (not including scores for anti-dsDNA antibody and hypocomplementemia), despite conventional treatment (e.g., immunosuppressants, antimalarial drugs, glucocorticoids, NSAIDs, anti-hypertensive drugs, and/or topical medications). In addition, subjects must be serologically active (positive anti-dsDNA antibody and/or hypocomplementemia).
Subjects will be randomly assigned by 1:1 ratio to receive sirolimus (1.5mg/day) or placebo for the first 24-week phase. In the second 24-week open-labeled phase, sirolimus patients receive the same dose of sirolimus, and placebo group are switched to receive sirolimus at 1.5mg/day
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sirolimus plus SOC | Experimental | Drug: SirolimusSirolimus plus standard therapy (SOC) for SLE; Generic name: sirolimus (0.5mg capsule); Dosage: 1.5mg/day; Administration route: Oral |
| Placebo plus SOC | Placebo comparator | Drug: PlaceboPlacebo plus standard therapy (SOC) for SLE; Drug: Placebo comparator plus SOC; Administration route: Oral |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (18 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusAlso: rapamycinIn 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. | Drug | Sirolimus plus SOC |
| PlaceboIn 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. | Drug | Placebo plus SOC |
Primary outcome
The Proportion of Patients Who Achieve an SLE Responder Index-4 (SRI-4) Composite Response at Week 24
Time frame: 24 weeks
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).
5 secondary outcomes
Change From Baseline in Complement Level at Week 24
Time frame: 24 weeks
Change From Baseline in Titers of Anti-dsDNA Antibody 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
Change From Baseline in Physician's Global Assessment of Disease Activity (PGA) 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2025.
- Individual participant dataSharing planned: Yes. all IPD that underlie results in a publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaofeng Zeng, MD principal investigator
Chinese SLE Treatment and Registration Group
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sirolimus in people with Systemic Lupus Erythematosus, run by Chinese SLE Treatment And Research Group at 6 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Proportion of Patients Who Achieve an SLE Responder Index-4 (SRI-4) Composite Response at Week 24 (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2025.