静脉输注异体人骨髓间充质干细胞治疗特发性肺纤维化（AETHER）：一项I期安全性临床试验
Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial.
作者信息
Glassberg Marilyn K, Minkiewicz Julia, Toonkel Rebecca L, Simonet Emmanuelle S, Rubio Gustavo A, DiFede Darcy, Shafazand Shirin, Khan Aisha, Pujol Marietsy V, LaRussa Vincent F, Lancaster Lisa H, Rosen Glenn D, Fishman Joel, Mageto Yolanda N, Mendizabal Adam, Hare Joshua M
机构信息
Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL; Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL; Department of Pediatrics, University of Miami Leonard M. Miller School of Medicine, Miami, FL.
Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL.
出版信息
Chest. 2017 May;151(5):971-981. doi: 10.1016/j.chest.2016.10.061. Epub 2016 Nov 24.
BACKGROUND
Despite Food and Drug Administration approval of 2 new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Preclinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition. The Allogeneic Human Cells (hMSC) in patients with Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER) trial was the first study designed to evaluate the safety of a single infusion of bone marrow-derived mesenchymal stem cells in patients with idiopathic pulmonary fibrosis.
METHODS
Nine patients with mild to moderate IPF were sequentially assigned to 1 of 3 cohorts and dosed with a single IV infusion of 20, 100, or 200 × 10 human bone marrow-derived mesenchymal stem cells per infusion from young, unrelated, men. All baseline patient data were reviewed by a multidisciplinary study team to ensure accurate diagnosis. The primary end point was the incidence (at week 4 postinfusion) of treatment-emergent serious adverse events, defined as the composite of death, nonfatal pulmonary embolism, stroke, hospitalization for worsening dyspnea, and clinically significant laboratory test abnormalities. Safety was assessed until week 60 and additionally 28 days thereafter. Secondary efficacy end points were exploratory and measured disease progression.
RESULTS
No treatment-emergent serious adverse events were reported. Two nontreatment-related deaths occurred because of progression of IPF (disease worsening and/or acute exacerbation). By 60 weeks postinfusion, there was a 3.0% mean decline in % predicted FVC and 5.4% mean decline in % predicted diffusing capacity of the lungs for carbon monoxide.
CONCLUSIONS
Data from this trial support the safety of a single infusion of human mesenchymal stem cells in patients with mild-moderate IPF.
TRIAL REGISTRY
ClinicalTrials.gov; No.: NCT02013700; URL: www.clinicaltrials.gov.
背景
尽管美国食品药品监督管理局已批准两种用于特发性肺纤维化（IPF）的新药，但治愈性疗法仍难以捉摸，死亡率依然很高。临床前和临床数据支持人骨髓间充质干细胞作为这种致命疾病潜在新疗法的安全性。特发性肺纤维化患者静脉输注异基因人细胞（hMSC）（AETHER）试验是首个旨在评估单次输注骨髓源性间充质干细胞对特发性肺纤维化患者安全性的研究。
方法
9例轻度至中度IPF患者被依次分配到3个队列中的1个，并接受单次静脉输注，每次输注来自年轻、无关男性供者的20×10、100×10或200×10人骨髓源性间充质干细胞。多学科研究团队对所有患者的基线数据进行了审查，以确保诊断准确。主要终点是输注后4周出现的治疗突发严重不良事件的发生率，其定义为死亡、非致命性肺栓塞、中风、因呼吸困难加重住院以及具有临床意义的实验室检查异常的综合情况。安全性评估至第60周，并在此后额外评估28天。次要疗效终点为探索性指标，用于衡量疾病进展。
结果
未报告治疗突发严重不良事件。因IPF进展（疾病恶化和/或急性加重）发生了2例与治疗无关的死亡。输注后60周时，预测用力肺活量（FVC）百分比平均下降3.0%，预测肺一氧化碳弥散量百分比平均下降5.4%。
结论
该试验数据支持单次输注人骨髓间充质干细胞对轻度至中度IPF患者的安全性。
试验注册
ClinicalTrials.gov；编号：NCT02013700；网址：www.clinicaltrials.gov 。
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