#AHA16 Randomized Comparison of Allogeneic vs. Autologous Mesenchymal Stem Cells for Non-lschemic Dilated Cardiomyopathy (POSEIDON-DCM Trial) Joshua M Hare, Darcy L DiFede, Angela M Castellanos, Victoria Florea, Ana M Landin, Jill El-Khorazaty, Aisha Khan, Muzammil Mushtaq, Maureen H Lowery, John J Byrnes, Robert C Hendel, Mauricio G Cohen, Carlos E Alfonso, Krystalenia Valasaki, Marietsy V Pujol, Samuel Golpanian, Eduard Ghersin, Joel E Fishman, Pradip Pattany, Samirah A Gomes, Cindy Delgado, Roberto Miki, Fouad Abuzeid, Mayra Vidro-Casiano , Courtney Premer, Audrey Medina, Valeria Porras, Konstantinos E Hatzistergos, Erica Anderson, Adam Mendizabal, Raul Mitrani, Alan W Heldman ISCI, University of Miami Miller School of Medicine / EMMES Corp. November 14, 2016 Funded by the NHLBI RO1 HL RO110737 Acknowledgements: Mark Martin, Doug Suehr, Jonathan Wong, Jim Taylor, BDS / NHLBI DSMB
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#AHA16
Randomized Comparison of Allogeneic vs. Autologous Mesenchymal Stem Cells for Non-lschemic Dilated
Cardiomyopathy (POSEIDON-DCM Trial)
Joshua M Hare, Darcy L DiFede, Angela M Castellanos, Victoria Florea, Ana M Landin, Jill El-Khorazaty, Aisha Khan, Muzammil Mushtaq, Maureen H Lowery, John J Byrnes, Robert C Hendel, Mauricio G Cohen, Carlos E Alfonso, Krystalenia Valasaki, MarietsyV Pujol, Samuel Golpanian, Eduard Ghersin, Joel E Fishman, Pradip Pattany, Samirah
A Gomes, Cindy Delgado, Roberto Miki, Fouad Abuzeid, Mayra Vidro-Casiano , Courtney Premer, Audrey Medina, Valeria Porras, Konstantinos E Hatzistergos, Erica
Anderson, Adam Mendizabal, Raul Mitrani, Alan W Heldman
ISCI, University of Miami Miller School of Medicine / EMMES Corp.November 14, 2016
Funded by the NHLBI RO1 HL RO110737
Acknowledgements: Mark Martin, Doug Suehr, Jonathan Wong, Jim Taylor, BDS / NHLBI DSMB
#AHA16
Background
• Non-ischemic dilated cardiomyopathy (NIDCM) is anincurable condition with significant genetic and immunologicunderpinning
• Mesenchymal Stem Cells (MSCs) are immunomodulatory /immunoprivileged, pro-regenerative cells that are safe andpromote reverse remodeling in ischemic CM
• POSEIDON-DCM is a randomized comparison of the safetyand efficacy of autologous vs. allogeneic bone marrow-derived hMSCs in NIDCM.
#AHA16
Methods
• Phase I/II, randomized comparison of alllogeneic (Allo)and autologous (Auto) hMSCs with 12m follow-up
• Institution: University of Miami• Patients: 37 with LV dysfunction due to NIDCM – Dec 2011
to July 2015• Interventions: Allo or Auto MSCs were delivered by
transendocardial stem cell injection (TESI) into 10 LV sitesby NOGA Catheter System
Study FlowChart57 Patients assessed for eligibility
20 Excluded:14 Did not meet inclusion criteria 4 Declined to participate2 Other reasons
37 Randomized 1:1
19 Randomized to receive allogeneic mesenchymal stem cell treatment
18 Randomized to receive autologous mesenchymal stem cell treatment
15 complete on year follow-up:3 withdrawn or lost to follow-up
12 completed one year follow-up:2 withdrawn or lost to follow-up2 deaths
18 Included in the primary analysis(30-day TE-SAEa)
16 Included in the primary analysis(30-day TE-SAEa)
18 Received treatment as randomized 1 Did not receive treatment as randomized:
1 death post randomization
16 Received treatment as randomized2 Did not receive treatment as randomized:
1 withdrew consent1 underwent AICD placement and could no longer be
injected
#AHA16
Endpoints
SAFETY–30 Day safety–1 Year safety–FEV-1
EFFICACY–Major Adverse Cardiac Event–6 Minute walk test–Peak VO2–Minnesota Living with Heart Failure Questionnaire–NYHA Class–Cardiac Imaging for Global and Regional analysis–Endothelial function–Immunologic status
#AHA16
Patient Characteristics by Cell TypeCell Type
Baseline Characteristics
Allo
(n=18)
Auto
(n=16)
Age at injection (years) 54.4 (±11.5) 57.4 (±11.0)
Gender
Male 14 (77.8%) 10 (62.5%)
Female 4 (22.2%) 6 (37.5%)
Years of NIDCM diagnosis before TESI 6.05 (±6.2) 6.93 (±7.3)
History of adriamycin chemotherapy 1 (5.5%) 2 (12.5%)
AICD or BIV/CRT 15 (83.3%) 14 (87.5%)
End Diastolic Diameter (cm) 7.2 (±1.3) 7.1 (±1.7)
History of Coronary Interventions 2 (11.1%) 1 (6.3%)
Previously Referred for AICD Placement 15 (83.3%) 14 (87.5%)
History of Atrial or Ventricular Arrhythmia 5 (27.8%) 1 (6.3%)
History of Hypertension 7 (38.9%) 3 (18.8%)
New York Heart Association Class
Class I - No Limitation 4 (22.2%) 6 (37.5%)
Class II - Slight Limitation of Physical Activity 9 (50.0%) 8 (50.0%)
Class III - Marked Limitation of Physical
Activity
5 (27.8%) 2 (12.5%)
History of Congestive Heart Failure 11 (61.1%) 7 (43.8%)
#AHA16
SAFETY
Safety Summary Post-TESI Allo (n=18) Auto (n=16)
n % (95% CI) n % (95% CI) Day 30 Post-TESI
Incidence of AE 7 38.9% (20.8-64.7) 4 25.0% (10.2-53.7)
Incidence of SAE 2 11.1% (2.9-37.6) 1 6.3% (0.9-36.8) Incidence of TE-SAE 0 0.0% (0.0-18.5) 0 0.0% (0.0-20.6)
Incidence of MACE 0 0.0% (0.0-18.5) 0 0.0% (0.0-20.6) Day 180 Post-TESI
Incidence of AE 12 66.7% (45.5-86.3) 11 68.8% (46.4-88.6) Incidence of SAE 4 22.2% (9.0-48.9) 4 25.0% (10.2-53.7)
Incidence of MACE 1 5.6% (0.8-33.4) 3 18.8% (6.5-47.5)
Incidence of Death 0 0.0% (0.0-18.5) 1 6.3% (0.9-36.)
Day 365 Post-TESI
Incidence of AE 12 66.7% (45.5-86.3) 12 75.0% (52.8-92.2) Incidence of SAE 5 28.2% (12.8-55.1) 10 63.5% (40.8-85.7)
Incidence of MACE 3 20.3% (6.8-52.1)ϯ 9 57.1% (34.9-81.2)
Incidence of Death 0 0.0% (0.0-18.5) 2 12.5% (3.3-41.4)