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Original Research: Diffuse Lung Disease |

Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial

Marilyn K. Glassberg, MD; Julia Minkiewicz, PhD; Rebecca L. Toonkel, MD; Emmanuelle S. Simonet, MA; Gustavo A. Rubio, MD; Darcy DiFede, RN, BSN; Shirin Shafazand, MD; Aisha Khan, PhD; Marietsy V. Pujol, MBA; Vincent F. LaRussa, PhD; Lisa H. Lancaster, MD; Glenn D. Rosen, MD; Joel Fishman, MD, PhD; Yolanda N. Mageto, MD, MPH; Adam Mendizabal, PhD; Joshua M. Hare, MD
Author and Funding Information

FUNDING/SUPPORT: Financial support for the AETHER trial came from the Lester and Sue Smith Foundation.

aDepartment of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL

bDepartment of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL

cDepartment of Pediatrics, University of Miami Leonard M. Miller School of Medicine, Miami, FL

dDepartment of Medicine, Florida International University Herbert Wertheim College of Medicine, Miami, FL

eUniversity of Miami Interdisciplinary Stem Cell Institute, Miami, FL

fDepartment of Cardiology, University of Louisville, Louisville, KY

gDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN

hBristol-Myers Squibb, Lawrenceville, NJ

iDepartment of Medicine, University of Vermont College of Medicine, Burlington, VT

jThe EMMES Corporation, Rockville, MD

CORRESPONDENCE TO: Marilyn Glassberg, MD, Department of Medicine, Interstitial Lung Disease Program, University of Miami Miller School of Medicine. 1600 NW 10th Ave RMSB 7056 (D-60), Miami, FL 33136


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2017;151(5):971-981. doi:10.1016/j.chest.2016.10.061
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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 × 106 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.

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