0
Original Research |

Allogeneic human mesenchymal stem cells in patients with idiopathic pulmonary fibrosis via intravenous delivery (AETHER): a phase I, safety, clinical trial

Marilyn K. Glassberg, M.D.; Julia Minkiewicz, Ph.D.; Rebecca L. Toonkel, M.D.; Emmanuelle S. Simonet, M.A.; Gustavo A. Rubio, M.D.; Darcy Difede, R.N., B.S.N.; Shirin Shafazand, M.D.; Aisha Khan, Ph.D.; Marietsy V. Pujol, M.B.A.; Vincent F. LaRussa, Ph.D.; Lisa H. Lancaster, M.D.; Glenn D. Rosen, M.D.; Joel Fishman, M.D., Ph.D.; Yolanda N. Mageto, M.D., M.P.H.; Adam Mendizabal, Ph.D.; Joshua M. Hare, M.D.
Author and Funding Information

Summary of conflict of interests: MK Glassberg is currently participating in a role of an investigator at industry-sponsored clinical trials for Genentech, Boehringer Ingelheim, Bayer and Biogen. MK Glassberg serves as a consultant expert for Genentech and Boehringer Ingelheim. LH Lancaster served as an investigator for Boehringer Ingelheim, Genentech, Global Blood Therapeutics, Celgene, Roche and Veracyte. She has also served on advisory boards for Genentech and Boehringer Ingelheim. YN Mageto has served on the speakers bureau for Boehringer Ingelheim. All other authors have indicated no conflict of interest.

Funding: Financial support for the AETHER trial came from the Lester and Sue Smith Foundation.

ClinicalTrials.gov identifier NCT02013700

1Department of Medicine, University of Miami Miller School of Medicine

2Surgery, University of Miami Miller School of Medicine

3Pediatrics, University of Miami Miller School of Medicine

4Department of Medicine, Florida International University Herbert Wertheim College of Medicine

5University of Miami Interdisciplinary Stem Cell Institute

6Department of Cardiology, University of Louisville

7Department of Medicine, Vanderbilt University Medical Center

8Bristol-Myers Squibb

9Department of Medicine, University of Vermont College of Medicine

10The EMMES Corporation

Correspondence to: Marilyn Glassberg, M.D. Department of Medicine, Interstitial Lung Disease Program, University of Miami Miller School of Medicine. 1600 NW 10th Avenue RMSB 7056 (D-60), Miami, FL 33136, USA.


Copyright 2016, . All Rights Reserved.


Chest. 2016. doi:10.1016/j.chest.2016.10.061
Text Size: A A A
Published online

Abstract

Background  Despite recent FDA approval of two new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Pre-clinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition. The 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 one of three cohorts and dosed with a single intravenous infusion of 20, 100, or 200 x 106 human bone marrow-derived mesenchymal stem cells per infusion from young, unrelated, male donors. All baseline patient data were reviewed by a multidisciplinary study team to ensure accurate diagnosis. The primary endpoint was the incidence (at week four post infusion) of treatment emergent serious adverse events, defined as the composite of: death, non-fatal 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 endpoints were exploratory and measured disease progression.

Results  No treatment-emergent serious adverse events were reported. Two non-treatment related deaths occurred due to progression of IPF (disease worsening and/or acute exacerbation). By 60 weeks post-infusion, there was a 3.0% mean decline in % predicted FVC and 5.4% mean decline in % predicted DLCO.

Conclusions  Data from this trial support the safety of a single infusion of hMSC in patients with mild-moderate IPF.


Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543