This is a Phase IIA, randomized, double blind, placebo controlled, multicenter study designed to assess the safety, feasibility, and efficacy of umbilical cord derived mesenchymal stromal cells (UC MSCs), administered intravenously (IV) as a single dose or repeated doses, in patients with ischemic cardiomyopathy (ICM).
This is a Phase IIA, randomized, double blind, placebo controlled, multicenter study designed to assess the safety, feasibility, and efficacy of umbilical cord derived mesenchymal stromal cells (UC MSCs), administered intravenously (IV) as a single dose or repeated doses, in patients with ischemic cardiomyopathy (ICM) (see summary in Figure 1). A total of 60 participants will be assigned in a random fashion to three groups on a 1:1:1 basis: control, single dose, and repeated doses. All patients will receive four study product infusions (SPIs) 2 months apart. SPIs (performed in a double blind fashion) will consist of either UC MSCs or placebo (based on randomization), infused by the IV route. Patients in the control group will receive four doses of placebo. Patients in the single dose group will receive one dose of UC MSCs followed by three doses of placebo. Patients in the repeated dose group will receive four doses of UC MSCs. A dose of UC MSCs will consist of 100 million cells suspended in 60 mL, infused at a rate of 2 mL/min. A dose of placebo will consist of an equivalent volume of Plasma Lyte A supplemented with 1% human serum albumin (HSA). After each SPI, patients will be monitored for a minimum of 2 hours and then examined at 1 week and 2 months. After the fourth SPI, patients will be followed for 6 months to complete all safety and efficacy assessments. The UC MSCs will be derived from UC tissue obtained from a healthy pregnant woman at the time of caesarean delivery. The cells will be manufactured at the Interdisciplinary Stem Cell Institute at the University of Miami, Miller School of Medicine and then shipped to the Site for administration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
60
The study product will consist of 100 million UC-MSCs suspended in a final volume of 60 ml given at a rate of 3.3 million cells/min. The product will be infused into vein via intravenous line placed in the arm.
University of Miami Miller School of Medicine
Miami, Florida, United States
RECRUITINGUniversity of Louisville School of Medicine, Institute of Molecular Cardiology
Louisville, Kentucky, United States
RECRUITINGThe Texas Heart Institute Houston Texas
Houston, Texas, United States
RECRUITINGchange in LVEF (D LVEF) between baseline (M0) and 12 months after the first study product infusion (SPI) (M12)
Change in left ventricular ejection fraction as assessed via cardiac MRI. Units: %
Time frame: Baseline, 12 months
Change in LV end-systolic volume index (ESVI)
Change in left ventricular end systolic index (LVESVI) as assessed via cardiac MRI. Units: ml/m2
Time frame: Baseline, 12 months
Change in LV end-diastolic volume index (EDVI)
Change in left ventricular end diastolic index (LVEDVI) as assessed via cardiac MRI. Units: ml/m2
Time frame: Baseline, 12 months
Change in LV end-diastolic wall thickness
Change in LV end-diastolic wall thickness as assessed via cardiac MRI. Units: mm
Time frame: Baseline, 12 months
Change in LV wall thickening
Change in LV wall thickening as assessed via cardiac MRI. Units: mm
Time frame: Baseline, 12 months
Change in LV sphericity index
Change in LV sphericity index as assessed via cardiac MRI. Units: Index score Sphericity index is the ratio of the long and short axis measurements of the left ventricle.
Time frame: Baseline, 12 months
Change in global and regional strain (tagged MRI): global and 16-segment values for peak circumferential strain, global and segmental longitudinal strain
Change in global and regional strain as assessed via cardiac MRI. Units: %
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Time frame: Baseline, 12 months
Change in scar mass (in grams)
Change in scar mass (in grams) as assessed via delayed gadolinium enhancement MRI. Units: grams
Time frame: Baseline, 12 months
Change in scar mass (as %LV)
Change in scar mass (as %LV) as assessed via delayed gadolinium enhancement MRI. Units: %
Time frame: Baseline, 12 months
Change in VO2 max (treadmill test)
Change in maximal oxygen consumption (peak VO2) as assessed via treadmill. Units: mL/kg/min
Time frame: Baseline, month 8, month 12
Change in exercise tolerance (six-minute walk test)
Change in exercise tolerance as assessed as the distance covered via the six-minute walk test. Units: meters
Time frame: Baseline, month 8, month 12
Change in New York Heart Association class
NYHA Classifications of heart failure are as follows: Class I (no limitations); Class II (mild symptoms); Class III (marked limitations); Class IV (Severe limitations). Units: score on a scale
Time frame: Baseline, month 2,4,6,8, & 12
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score
KCCQ is a 12-item questionnaire in which scores are scaled from 0 to 100 and summarized in ranges to represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent. Units: score on a scale
Time frame: Baseline, month 6, month 12
Change in Endothelial Progenitor Cell [EPC]-colony forming unit [EPC-CFU] assay
Change in endothelial function will be reported as the change in Endothelial Progenitor Cell Colony Forming Unit (EPC-CFU) assessed via blood sample assay. Units: CFUs/well
Time frame: Baseline, month 2, 8, & 12
Change in branchial artery flow-mediated dilation [FMD] [diameter percent change]).
Change in branchial artery flow-mediated dilation will be reported as the percent change in flow mediated diameter assessed via flow mediated dilation (FMD). Units: %
Time frame: Baseline, month 2, 8, & 12
Major adverse cardiac events (MACE)
Number of participants with adjudicated events including death, hospitalization for worsening HF, and exacerbation of HF requiring visit to the Emergency Department and/or IV therapy but not requiring hospitalization. Units: number of participants who have an incidence of MACE in each group
Time frame: Month 12
Cumulative days alive and out of hospital for HF
Days alive and out of hospital during the study evaluation period. Units: days
Time frame: Month 12
Biomarkers: Change in NT-proBNP
Change in NT-proBNP as assessed via blood draw. Units: pg/ml
Time frame: Day 0, Month 2, 4, 6, 8, & 12
Biomarkers: hs-CRP
Blood level of hs-CRP as assessed via blood draw. Units: mg/ml
Time frame: Day 0, Week 1, Month 2, 4, 6, 8, & 12