A Phase II Controlled Trial of Allogeneic Mesenchymal Stem Cells for the Treatment of Refractory Lupus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 9
- 主要终点
- Clinical response at Week 24 as defined by the SLE Responder Index (SRI):
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of mesenchymal stem cells (MSCs) obtained from umbilical cords for the treatment of adults with systemic lupus erythematosus (SLE). The goal of this study is to determine if patients receiving an MSC infusion plus standard of care respond better than patients receiving placebo infusion plus standard of care.
详细描述
A phase 2 multicenter (several medical research centers participating), placebo controlled, randomized (assigned by chance), double blind (neither the participant nor the investigator will know if active drug or placebo is assigned) trial to evaluate the safety and efficacy of mesenchymal stem cells (MSCs) for the treatment of systemic lupus erythematosus (SLE) in adults.
The MSCs will be obtained from healthy donor umbilical cords and two doses of MSCs will be tested. The cells will be produced at the Medical University of South Carolina (MUSC) and will be shipped to other participating centers for patients with SLE. Participants will receive either active drug or placebo through a single IV infusion. All participants will receive standard of care and their safety will be monitored throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients between 18 and 65 years old, male or female, of any race
- •Historical presence of at least 4 of 11 of the ACR Classification Criteria
- •Evidence of a positive ANA (≥1:80 titer) or positive dsDNA antibody test within 6 months of screening
- •Clinically active SLE determined by SLEDAI score ≥6 and the presence of at least one BILAG A or BILAG B at screening, despite standard-of-care therapy
- •If the patient has a BILAG A or BILAG B score in the renal organ system, he/she must have completed at least 6 months of therapy for the current episode of nephritis prior to Screening. Therapy must include at least 6 months of mycophenolate or at least 3 months of cyclophosphamide followed by mycophenolate or azathioprine
- •Able and willing to give written informed consent
排除标准
- •Active CNS lupus affecting mental status
- •Active lupus nephritis requiring dialysis
- •Laboratory exclusions: eGFR <30, WBC <2.0/mm3, hemoglobin <8 g/dL, platelet count <30,000/mm3, liver enzymes AST or ALT >4 times upper limit normal.
- •Positive testing for HIV, hepatitis B or hepatitis C, tuberculosis (TB), or chest X-ray (CXR) findings consistent with TB or latent fungal infection.
- •History of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix
- •Pregnant or breast feeding
- •A woman of childbearing potential (not post-menopausal or surgically sterile) who is not willing to use adequate contraception
- •History of renal transplantation
- •Herpes zoster within the past 90 days or any infection requiring hospitalization or intravenous or intramuscular antibiotics within the past 60 days
- •Clinically significant EKG or chest X-ray changes
- •Any other medical condition, related or unrelated to SLE, that in the opinion of the investigator would render the patient inappropriate or too unstable to complete study protocol
- •Use of prednisone >0.5 mg/kg/day (or equivalent corticosteroid) within 1 month of Baseline visit
- •Change or addition to immunosuppressant regimen within 3 months of Baseline visit (except corticosteroids); Use of other experimental therapeutic agents within 3 months of Baseline visit
- •Having received belimumab within 2 months of Baseline, or having received rituximab or other B cell depleting biologic therapy within 6 months of Baseline.
- •Comorbidities requiring corticosteroid therapy
- •Current substance abuse or recent (within one year) history of substance abuse
研究组 & 干预措施
Low Dose Mesenchymal Stem Cells (MSCs)
Mesenchymal Stem Cells (MSCs) 1 x 10^6 cells/kg in Plasma-Lyte A solution
干预措施: Low Dose Mesenchymal Stem Cells (MSCs) (Drug)
High Dose Mesenchymal Stem Cells (MSCs)
Mesenchymal Stem Cells MSCs 5 x 10^6 cells/kg in Plasma-Lyte A solution
干预措施: High Dose Mesenchymal Stem Cells (MSCs) (Drug)
Plasma Lyte A Solution
Placebo Infusion (Plasma-Lyte A solution only)
干预措施: Placebo Infusion (Drug)
结局指标
主要结局
Clinical response at Week 24 as defined by the SLE Responder Index (SRI):
时间窗: Week 24
Systemic Lupus Erythematosus Responder Index (SRI) is defined as a greater than or equal to (≥) 4 point reduction in the Systemic Lupus Erythematosus Disease Activity Index score (SLEDAI), no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B domain score, and no deterioration from Baseline in the Physician's Global Assessment (PGA) by greater than or equal to (≥) 0.3 points. Additionally, to be a "responder", corticosteroid dose must be less than of equal to (≤)10 mg/day of prednisone or equivalent by the Week 20 visit and be maintained at less than or equal to 10 mg/day through Week 24.
次要结局
- Cumulative systemic steroid dose(Week 52)
- Changes in Depression(Baseline to Week 52)
- Steroid-sparing effect(Baseline to Week 52)
- Change in SLEDAI score between groups(Baseline to Weeks 12, 24, and 52)
- Changes in SLICC-DI(Baseline to Week 52)
- Changes in HR-QOL(Baseline to Week 52)
- Changes in patient-reported lupus-specific disease status(Baseline to Week 52)
- Renal and non-renal organ system flares(At or before Weeks 12, 24, and 52)
- Changes in Fatigue(Baseline to Week 52)
- Changes in the presence of serum and urine biomarkers of SLE activity:(Baseline to Week 52)
- Changes in Pain(Baseline to Week 52)
研究者
Gary Gilkeson
Professor-Faculty
Medical University of South Carolina