Efficacy and Safety of Sirolimus in Active Systemic Lupus Erythematosus

Phase 3Active Not RecruitingNCT04582136

Chinese SLE Treatment And Research Group146 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

146

Conditions

Systemic Lupus Erythematosus

Interventions

SirolimusDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (6)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Shenzhen People's Hospital

Shenzhen, Guangdong, China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Outcomes

Primary Outcomes

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).

Time frame: 24 weeks

Secondary Outcomes

Change From Baseline in Complement Level at Week 24

Serum complement refers to C3 and C4, which are both detected in the central lab.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 24 weeks

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.