Efficacy and Safety of Allogeneic Mesenchymal Precursor Cells (Rexlemestrocel-L) for the Treatment of Heart Failure.

Phase 3

Completed

Conditions: Chronic Heart Failure

Interventions: Biological: Allogeneic Mesenchymal Precursor Cells (MPCs)
Other: Sham Comparator

Registration Number: NCT02032004

Lead Sponsor: Mesoblast, Inc.

Brief Summary: The primary objective of this study is to determine whether transendocardial delivery of allogeneic human bone marrow-derived mesenchymal precursor cells (MPCs \[rexlemestrocel-L\]) is effective in the treatment of chronic heart failure (HF) due to left ventricular (LV) systolic dysfunction.

Detailed Description: The purpose of this study is to evaluate the efficacy and safety of a single transendocardial delivery in the cardiac catheterization laboratory of human bone marrow-derived allogeneic MPCs (rexlemestrocel-L) for improvement in clinical outcomes (heart failure major adverse cardiac events \[HF-MACE\]), preventing further adverse cardiac remodeling (left ventricular end systolic volume \[LVESV\] and left ventricular end-diastolic volume \[LVEDV\]), and increasing exercise capacity (six-minute walking test \[6MWT\]) in patients with chronic HF due to LV systolic dysfunction of either ischemic or nonischemic etiology who have received optimal medical/revascularization therapy.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 566

Inclusion Criteria

The patient is 18 to 80 years of age, inclusive; both men and women will be enrolled.
The patient has a diagnosis of chronic HF of ischemic or nonischemic etiology for at least 6 months
The patient is on stable, optimally tolerated dosages of HF therapies including beta-blockers (approved for country-specific usage), angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and/or aldosterone antagonists, without change in dose for at least 1 month before study intervention
The patient is on a stable, outpatient, oral diuretic dosing regimen in which the patient remains clinically stable during screening.
Other Criteria apply, please contact the investigator

Exclusion Criteria

The patient has NYHA Functional Class I or Functional Class IV symptoms.
Other Criteria apply, please contact the investigator

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Allogeneic Mesenchymal Precursor Cells	Allogeneic Mesenchymal Precursor Cells (MPCs)	Participants randomly assigned to treatment will undergo a single index cardiac catheterization involving transendocardial delivery of rexlemestrocel-L into the myocardium at a cell injection center by an interventional cardiology team not involved with review or assessment of subsequent study results.
Control Treatment	Sham Comparator	Participants randomly assigned to control treatment will undergo a single cardiac catheterization involving a scripted sham cardiac mapping and cell delivery procedure at a cell injection center by an interventional cardiology team not involved with review or assessment of subsequent study results.

Primary Outcome Measures

Name	Time	Method
Time to recurrent non-fatal decompensated heart failure major adverse cardiac events (HF-MACE) that occur prior to the first terminal cardiac event (TCE).	6 Month minimum

Secondary Outcome Measures

Name	Time	Method
Time-to-first terminal cardiac event (TCE)	6 Month minimum
Total length of in-hospital stay in intensive care unit for non-fatal decompensated HF events	6 Month minimum
Time-to-first HF-MACE (composite of hospital admissions for decompensated HF, urgent care outpatient HF visit, and successfully RCD events)	6 Month minimum
Time-to-hospital admissions for non-fatal decompensated HF events	6 Month minimum
Time-to-first HF-MACE (composite of hospital admissions for decompensated HF, urgent care outpatient HF visit, successfully RCD events or TCE)	6 Month minimum
Time-to-cardiac death	6 Month minimum
Time-to-all-cause death	6 Month minimum
Time-to-urgent care outpatient HF visits	6 Month minimum
Time-to-successfully resuscitated cardiac death (RCD) events	6 Month minimum
Left Ventricular (LV) remodeling in LVESV determined by 2-D echocardiography	Screening, day 0 (post-procedure), months 3, 6, and 12, and every 12 months thereafter during study conduct (6 Month minimum)
Correlations between baseline LVESV <=100 mL and LVESV >100 mL and clinical outcomes	6 Month minimum
Safety as assessed by occurrence of treatment-emergent adverse events	Screening through 6 Month minimum
Safety as assessed by urinalysis (blood, glucose, ketones, total protein)	Screening, day 10, months 1, 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)
Safety as assessed by vital signs (pulse, systolic blood pressure [BP], diastolic BP)	Screening, day 0 (pre and post-procedure), day 1, day 10, months 1, 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)
Time-to-first non-fatal MI (myocardial infarction), non-fatal CVA (cerebrovascular attack) or coronary artery revascularization	6 Month minimum
LV remodeling in LVEDV determined by 2-D echocardiography	Screening, day 0 (post-procedure), months 3, 6, and 12, and every 12 months thereafter during study conduct (6 Month minimum)
Overall Left Ventricular systolic performance as assessed by left ventricular ejection fraction (LVEF [radionuclide ventriculography {RVG} or echocardiogram])	Screening, day 0 (post-procedure), months 3, 6, and 12, and every 12 months thereafter during study conduct (6 Month minimum)
Correlations between baseline LVESV <=100 mL and LVESV >100 mL and change in Month 6 to baseline LVESV and clinical outcomes	6 Month minimum
Quality of Life Measure - European Quality of Life (EuroQoL) 5-dimensional (EQ-5D) questionnaire	Screening, months 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)
Safety as assessed by telemetry monitoring findings (clinically significant arrhythmias)	Day 0 through Day 0 overnight post-procedure
Safety as assessed by rhythm analysis (specifically, ventricular arrhythmias) by interrogation of any implanted device capable of defibrillation	Day 10, months 1, 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)
Safety as assessed by important cardiovascular events from adjudicated data	6 Month minimum
Functional exercise capacity as assessed by 6 Minute Walk Test	Screening, months 3, 6, and 12, and every 12 months thereafter during study conduct (6 Month minimum)
Functional status by New York Heart Association (NYHA) class	Screening, months 3, 6, and 12, and every 12 months thereafter during study conduct (6 Month minimum)
Quality of Life Measure - Minnesota Living With Heart Failure (MLHF) questionnaire	Screening, months 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)
Safety as assessed by occurrence of adverse events related to the index cardiac catheterization on Day 0	Day 0 through discharge from Day 0 hospitalization
Safety as assessed by clinical laboratory tests (serum chemistry - ALT, AST, alkaline phosphate, GGT, LDH, BUN, creatinine, uric acid, total bilirubin - and hematology - hematocrit, hemoglobin, WBCs, eosinophils, ANC, platelet count)	Screening, day 0 (post-procedure), day 10, months 1, 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)	ALT (alanine transaminase), AST (aspartate aminotransferase), GGT (gamma-glutamyl transferase), LDH (lactate dehydrogenase), BUN (blood urea nitrogen), WBCs (white blood cells), ANC (absolute neutrophil count)
Safety as assessed by 24-hr Holter monitoring (HR, rate & duration of arrhythmias, a-fib average rate, supra- & ventricular ectopy singles/couplets/runs/totals, sustained & non-sustained ventricular tachycardia, longest pauses RR duration, total pauses)	Screening, day 0 (post-procedure), day 10, months 1 and 3
Safety as assessed by 12-lead electrocardiogram (ECG) findings - QT interval with Fridericia's correction (QTcF), heart rate-corrected QT interval (QTcB), QT, Q wave, R wave and S wave (QRS) complex, HR and T waves.	Screening, day 0 (pre and post-procedure), day 1, day 10, months 1, 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)
Safety as assessed by physical examination findings judged as clinically significant changes from baseline by the investigator or newly occurring abnormalities (including weight)	Screening, month 12 and every 12 months thereafter until study conclusion (weight measured at screening, day 0 - pre and post-procedure, day 1, day 10, months 1, 3, 6 and 12 and every 6 months thereafter)

Trial Locations

Locations (59): Mesoblast Investigational Site 10775 - Cedars-Sinai Medical Care Foundation
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Los Angeles, California, United States
Mesoblast Investigational Site 13027 - Emory University School of Medicine
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Atlanta, Georgia, United States
Mesoblast Investigational Site 10772 - University Cardiologist, Rush University Medical Center
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Chicago, Illinois, United States
Mesoblast Investigational Site 13278 - OhioHealth Research Institute
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Columbus, Ohio, United States
Mesoblast Investigational Site 10782
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Boston, Massachusetts, United States
Mesoblast Investigational Site 10771 - Heart & Vascular Research, Swedish Medical Center
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Seattle, Washington, United States
Mesoblast Investigational Site 10755 - Texas Heart Institute
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Houston, Texas, United States
Mesoblast Investigational Site 13268 - Houston Methodist Hospital
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Houston, Texas, United States
Mesoblast Investigational Site 10768 - University of Miami
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Miami, Florida, United States
Mesoblast Investigational Site 13281
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Las Vegas, Nevada, United States
Mesoblast Investigational Site 10758 - The Christ Hospital
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Cincinnati, Ohio, United States
Mesoblast Investigational Site 10770 - University of Cincinnati
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Cincinnati, Ohio, United States
Mesoblast Investigational Site 10762 - Minneapolis Heart Institute
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Minneapolis, Minnesota, United States
Mesoblast Investigational Site 10781 - Duke University
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Durham, North Carolina, United States
Mesoblast Investigational Site 13023 - University of Arizona Medical Center
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Tucson, Arizona, United States
Mesoblast Investigational Site 11027
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Edmonton, Alberta, Canada
Mesoblast Investigational Site 10763 - University Hospital
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Salt Lake City, Utah, United States
Mesoblast Investigational Site 10757 - Cardiology, P.C.
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Birmingham, Alabama, United States
Mesoblast Investigational Site 13262 - University of Alabama at Birmingham Hospital
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Birmingham, Alabama, United States
Mesoblast Investigational Site 10754 - University of California, San Diego
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La Jolla, California, United States
Mesoblast Investigational Site 10759 - Scripps Clinic
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La Jolla, California, United States
Mesoblast Investigational Site 13265 - University of California, Los Angeles
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Los Angeles, California, United States
Mesoblast Investigational Site 13275 - Stanford University Hospital
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Stanford, California, United States
Mesoblast Investigational Site 13031 - St. John's Regional Medical Center
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Oxnard, California, United States
Mesoblast Investigational Site 10778 - Orange County Cardiology
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Orange, California, United States
Mesoblast Investigational Site 13273 - University of Florida Health
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Jacksonville, Florida, United States
Mesoblast Investigational Site 13267 - Bethesda Heart Hospital
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Boynton Beach, Florida, United States
Mesoblast Investigational Site 10780 - Morton Plant Hospital
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Clearwater, Florida, United States
Mesoblast Investigational Site 10760 - Shands Hospital, University of Florida
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Gainesville, Florida, United States
Mesoblast Investigational Site 10765 - Georgia Regents University
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Augusta, Georgia, United States
Mesoblast Investigational Site 13030 - University of Iowa
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Iowa City, Iowa, United States
Mesoblast Investigational Site 10783 - Gill Heart Institute, University of Kentucky
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Lexington, Kentucky, United States
Mesoblast Investigational Site 13022 - University of Louisville
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Louisville, Kentucky, United States
Mesoblast Investigational Site 13266
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New Orleans, Louisiana, United States
Mesoblast Investigational Site 10766 - Michigan Cardiovascular Institute
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Saginaw, Michigan, United States
Mesoblast Investigational Site 10761 - Mayo Clinic
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Rochester, Minnesota, United States
Mesoblast Investigational Site 13263 - RWJ Barnabas Heart Center
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Newark, New Jersey, United States
Mesoblast Investigational Site 10776 - Columbia University Medical Center
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New York, New York, United States
Mesoblast Investigational Site 10773
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Cleveland, Ohio, United States
Mesoblast Investigational Site 10785 - Lehigh Valley Hospital
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Allentown, Pennsylvania, United States
Mesoblast Investigational Site 10767 - Temple University Hospital
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Philadelphia, Pennsylvania, United States
Mesoblast Investigational Site 10777 - Stern Cardiovascular Foundation
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Germantown, Tennessee, United States
Mesoblast Investigational Site 10774 - University of Pittsburgh
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Pittsburgh, Pennsylvania, United States
Mesoblast Investigational Site 13024 - Austin Heart, PLLC
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Austin, Texas, United States
Mesoblast Investigational Site 13279
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Milwaukee, Wisconsin, United States
Mesoblast Investigational Site 10764 - University of Wisconsin
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Madison, Wisconsin, United States
Mesoblast Investigational Site 11025 - St. Michael's Hospital
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Toronto, Ontario, Canada
Mesoblast Investigational Site 13274 - Soltero CV Research Center, Baylor Scott & White Research Institute
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Dallas, Texas, United States
Mesoblast Investigational Site 10789 - Aspirus Research Institute
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Wausau, Wisconsin, United States
Mesoblast Investigational Site 13261 - University of Pennsylvania
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Philadelphia, Pennsylvania, United States
Mesoblast Investigational Site 13277
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Philadelphia, Pennsylvania, United States
Mesoblast Investigational Site 10779 - Mercy Gilbert Medical Center
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Gilbert, Arizona, United States
Mesoblast Investigational Site 10786 - Cardiovascular Associates of Mesa
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Mesa, Arizona, United States
Mesoblast Investigational Site 10756 - Mayo Clinic
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Phoenix, Arizona, United States
Mesoblast Investigational Site 11024 - Victoria Heart Institute Foundation
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Victoria, British Columbia, Canada
Mesoblast Investigational Site 13280
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Orlando, Florida, United States
Mesoblast Investigational Site 13264 - Florida Hospital Pepin Heart Institute
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Tampa, Florida, United States
Mesoblast Investigational Site 13026 - Sanger Heart and Vascular Institute, Carolinas Healthcare System
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Charlotte, North Carolina, United States
Mesoblast Investigational Site 10769 - Aurora Healthcare
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Milwaukee, Wisconsin, United States