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
Overview
- Phase
- Phase 3
- Intervention
- Sirolimus
- Conditions
- Systemic Lupus Erythematosus
- Sponsor
- Chinese SLE Treatment And Research Group
- Enrollment
- 146
- Locations
- 6
- Primary Endpoint
- The Proportion of Patients Who Achieve an SLE Responder Index-4 (SRI-4) Composite Response at Week 24
- Status
- Active, not recruiting
- Last Updated
- 7 months ago
Overview
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.
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
Investigators
Xiaofeng Zeng
Director of Rheumatology and Immunology Department Chinese Academy of Medical Sciences &Peking Union Medical College Hospital
Chinese SLE Treatment And Research Group
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;
Arms & Interventions
Sirolimus plus SOC
Sirolimus plus standard therapy (SOC) for SLE; Generic name: sirolimus (0.5mg capsule); Dosage: 1.5mg/day; Administration route: Oral
Intervention: Sirolimus
Placebo plus SOC
Placebo plus standard therapy (SOC) for SLE; Drug: Placebo comparator plus SOC; Administration route: Oral
Intervention: Placebo
Outcomes
Primary Outcomes
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).
Secondary Outcomes
- 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)
- Change From Baseline in Complement Level at Week 24(24 weeks)