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

Marilyn K Glassberg Csete, Julia Minkiewicz, Rebecca L. Toonkel, Emmanuelle S. Simonet, Gustavo A. Rubio, Darcy DiFede, Shirin Shafazand, Aisha Khan, Marietsy V. Pujol, Vincent F. LaRussa, Lisa H. Lancaster, Glenn D. Rosen, Joel Fishman, Yolanda N. Mageto, Adam Mendizabal, Joshua Hare

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)971-981
Number of pages11
JournalChest
Volume151
Issue number5
DOIs
StatePublished - May 1 2017

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Idiopathic Pulmonary Fibrosis
Clinical Trials, Phase I
Mesenchymal Stromal Cells
Safety
Lung Volume Measurements
Drug Approval
Bone and Bones
United States Food and Drug Administration
Therapeutics
Carbon Monoxide
Pulmonary Embolism
Dyspnea
Lung Diseases
Registries
Disease Progression
Hospitalization
Stroke
Mortality
Incidence
Pharmaceutical Preparations

Keywords

  • bone marrow
  • idiopathic pulmonary fibrosis
  • mesenchymal stem cells
  • safety trial

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

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

In: Chest, Vol. 151, No. 5, 01.05.2017, p. 971-981.

Research output: Contribution to journalArticle

Glassberg Csete, MK, Minkiewicz, J, Toonkel, RL, Simonet, ES, Rubio, GA, DiFede, D, Shafazand, S, Khan, A, Pujol, MV, LaRussa, VF, Lancaster, LH, Rosen, GD, Fishman, J, Mageto, YN, Mendizabal, A & Hare, J 2017, 'Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial', Chest, vol. 151, no. 5, pp. 971-981. https://doi.org/10.1016/j.chest.2016.10.061
Glassberg Csete, 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. / Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER) : A Phase I Safety Clinical Trial. In: Chest. 2017 ; Vol. 151, No. 5. pp. 971-981.
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abstract = "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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T2 - A Phase I Safety Clinical Trial

AU - Glassberg Csete, Marilyn K

AU - Minkiewicz, Julia

AU - Toonkel, Rebecca L.

AU - Simonet, Emmanuelle S.

AU - Rubio, Gustavo A.

AU - DiFede, Darcy

AU - Shafazand, Shirin

AU - Khan, Aisha

AU - Pujol, Marietsy V.

AU - LaRussa, Vincent F.

AU - Lancaster, Lisa H.

AU - Rosen, Glenn D.

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AU - Hare, Joshua

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N2 - 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.

AB - 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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