Clinical trial NCT02032004: Efficacy and Safety of Allogeneic Mesenchymal Precursor Cells (Rexlemestrocel-L) for the Treatment of Heart Failure.
Official title: Double-blind, Randomized, Sham-procedure-controlled, Parallel-Group Efficacy and Safety Study of Allogeneic Mesenchymal Precursor Cells (Rexlemestrocel-L) in Chronic Heart Failure Due to LV Systolic Dysfunction (Ischemic or Nonischemic) Dream HF-1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Heart Failure
Keywords: Chronic Heart Failure
CHF
Left Ventricular Systolic Dysfunction
Ischemic Heart Failure
Nonischemic Heart Failure
Stem Cells
Allogeneic Mesenchymal Precursor Cells
Lead sponsor: Mesoblast, Ltd.
Sponsor class: INDUSTRY
First posted: 2014-01-09
Enrollment: 566
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to recurrent non-fatal decompensated heart failure major adverse cardiac events (HF-MACE) that occur prior to the first terminal cardiac event (TCE).
timeFrame: 6 Month minimum
Secondary outcomes:
measure: Time-to-first terminal cardiac event (TCE)
timeFrame: 6 Month minimum
measure: Time-to-hospital admissions for non-fatal decompensated HF events
timeFrame: 6 Month minimum
measure: Time-to-urgent care outpatient HF visits
timeFrame: 6 Month minimum
measure: Time-to-successfully resuscitated cardiac death (RCD) events
timeFrame: 6 Month minimum
measure: Total length of in-hospital stay in intensive care unit for non-fatal decompensated HF events
timeFrame: 6 Month minimum
measure: Time-to-first HF-MACE (composite of hospital admissions for decompensated HF, urgent care outpatient HF visit, and successfully RCD events)
timeFrame: 6 Month minimum
measure: Time-to-first HF-MACE (composite of hospital admissions for decompensated HF, urgent care outpatient HF visit, successfully RCD events or TCE)
timeFrame: 6 Month minimum
measure: Time-to-cardiac death
timeFrame: 6 Month minimum
measure: Time-to-all-cause death
timeFrame: 6 Month minimum
measure: Time-to-first non-fatal MI (myocardial infarction), non-fatal CVA (cerebrovascular attack) or coronary artery revascularization
timeFrame: 6 Month minimum
measure: Left Ventricular (LV) remodeling in LVESV determined by 2-D echocardiography
timeFrame: Screening, day 0 (post-procedure), months 3, 6, and 12, and every 12 months thereafter during study conduct (6 Month minimum)
measure: Correlations between baseline LVESV <=100 mL and LVESV >100 mL and clinical outcomes
timeFrame: 6 Month minimum
measure: Correlations between baseline LVESV <=100 mL and LVESV >100 mL and change in Month 6 to baseline LVESV and clinical outcomes
timeFrame: 6 Month minimum
measure: LV remodeling in LVEDV determined by 2-D echocardiography
timeFrame: Screening, day 0 (post-procedure), months 3, 6, and 12, and every 12 months thereafter during study conduct (6 Month minimum)
measure: Overall Left Ventricular systolic performance as assessed by left ventricular ejection fraction (LVEF [radionuclide ventriculography {RVG} or echocardiogram])
timeFrame: Screening, day 0 (post-procedure), months 3, 6, and 12, and every 12 months thereafter during study conduct (6 Month minimum)
measure: Functional exercise capacity as assessed by 6 Minute Walk Test
timeFrame: Screening, months 3, 6, and 12, and every 12 months thereafter during study conduct (6 Month minimum)
measure: Functional status by New York Heart Association (NYHA) class
timeFrame: Screening, months 3, 6, and 12, and every 12 months thereafter during study conduct (6 Month minimum)
measure: Quality of Life Measure - Minnesota Living With Heart Failure (MLHF) questionnaire
timeFrame: Screening, months 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)
measure: Quality of Life Measure - European Quality of Life (EuroQoL) 5-dimensional (EQ-5D) questionnaire
timeFrame: Screening, months 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)
measure: Safety as assessed by occurrence of adverse events related to the index cardiac catheterization on Day 0
timeFrame: Day 0 through discharge from Day 0 hospitalization
measure: Safety as assessed by occurrence of treatment-emergent adverse events
timeFrame: Screening through 6 Month minimum
measure: 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)
timeFrame: Screening, day 0 (post-procedure), day 10, months 1, 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)
measure: Safety as assessed by urinalysis (blood, glucose, ketones, total protein)
timeFrame: Screening, day 10, months 1, 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)
measure: Safety as assessed by vital signs (pulse, systolic blood pressure [BP], diastolic BP)
timeFrame: 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)
measure: 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.
timeFrame: 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)
measure: Safety as assessed by telemetry monitoring findings (clinically significant arrhythmias)
timeFrame: Day 0 through Day 0 overnight post-procedure
measure: Safety as assessed by rhythm analysis (specifically, ventricular arrhythmias) by interrogation of any implanted device capable of defibrillation
timeFrame: Day 10, months 1, 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)
measure: 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)
timeFrame: Screening, day 0 (post-procedure), day 10, months 1 and 3
measure: Safety as assessed by physical examination findings judged as clinically significant changes from baseline by the investigator or newly occurring abnormalities (including weight)
timeFrame: 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)
measure: Safety as assessed by important cardiovascular events from adjudicated data
timeFrame: 6 Month minimum
Other outcomes:
measure: Pharmacodynamics Measures (N-terminal (NT)-pro hormone BNP [NT-proBNP] and high-sensitivity C-reactive protein [hs-CRP])
timeFrame: Screening, months 3, 6, 12 and every 12 months thereafter until study conclusion
measure: Pharmacogenomics (PGx) Analysis
timeFrame: Screening (only from those subjects who provide consent to participate in PGx sample collection)
measure: Immunogenicity Measures (panel reactive antibodies, donor specific antibody, if panel-reactive antibody (PRA) test is positive, antibodies against bovine and murine products)
timeFrame: Screening, day 10, months 1, 3, 6, and 12
Locations:
city: Birmingham
country: United States
facility: Mesoblast Investigational Site 10757 - Cardiology, P.C.
state: Alabama
city: Birmingham
country: United States
facility: Mesoblast Investigational Site 13262 - University of Alabama at Birmingham Hospital
state: Alabama
city: Gilbert
country: United States
facility: Mesoblast Investigational Site 10779 - Mercy Gilbert Medical Center
state: Arizona
city: Mesa
country: United States
facility: Mesoblast Investigational Site 10786 - Cardiovascular Associates of Mesa
state: Arizona
city: Phoenix
country: United States
facility: Mesoblast Investigational Site 10756 - Mayo Clinic
state: Arizona
city: Tucson
country: United States
facility: Mesoblast Investigational Site 13023 - University of Arizona Medical Center
state: Arizona
city: La Jolla
country: United States
facility: Mesoblast Investigational Site 10754 - University of California, San Diego
state: California
city: La Jolla
country: United States
facility: Mesoblast Investigational Site 10759 - Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: Mesoblast Investigational Site 13265 - University of California, Los Angeles
state: California
city: Los Angeles
country: United States
facility: Mesoblast Investigational Site 10775 - Cedars-Sinai Medical Care Foundation
state: California
city: Orange
country: United States
facility: Mesoblast Investigational Site 10778 - Orange County Cardiology
state: California
city: Oxnard
country: United States
facility: Mesoblast Investigational Site 13031 - St. John's Regional Medical Center
state: California
city: Stanford
country: United States
facility: Mesoblast Investigational Site 13275 - Stanford University Hospital
state: California
city: Boynton Beach
country: United States
facility: Mesoblast Investigational Site 13267 - Bethesda Heart Hospital
state: Florida
city: Clearwater
country: United States
facility: Mesoblast Investigational Site 10780 - Morton Plant Hospital
state: Florida
city: Gainesville
country: United States
facility: Mesoblast Investigational Site 10760 - Shands Hospital, University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mesoblast Investigational Site 13273 - University of Florida Health
state: Florida
city: Miami
country: United States
facility: Mesoblast Investigational Site 10768 - University of Miami
state: Florida
city: Orlando
country: United States
facility: Mesoblast Investigational Site 13280
state: Florida
city: Tampa
country: United States
facility: Mesoblast Investigational Site 13264 - Florida Hospital Pepin Heart Institute
state: Florida
city: Atlanta
country: United States
facility: Mesoblast Investigational Site 13027 - Emory University School of Medicine
state: Georgia
city: Augusta
country: United States
facility: Mesoblast Investigational Site 10765 - Georgia Regents University
state: Georgia
city: Chicago
country: United States
facility: Mesoblast Investigational Site 10772 - University Cardiologist, Rush University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: Mesoblast Investigational Site 13030 - University of Iowa
state: Iowa
city: Lexington
country: United States
facility: Mesoblast Investigational Site 10783 - Gill Heart Institute, University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Mesoblast Investigational Site 13022 - University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Mesoblast Investigational Site 13266
state: Louisiana
city: Boston
country: United States
facility: Mesoblast Investigational Site 10782
state: Massachusetts
city: Saginaw
country: United States
facility: Mesoblast Investigational Site 10766 - Michigan Cardiovascular Institute
state: Michigan
city: Minneapolis
country: United States
facility: Mesoblast Investigational Site 10762 - Minneapolis Heart Institute
state: Minnesota
city: Rochester
country: United States
facility: Mesoblast Investigational Site 10761 - Mayo Clinic
state: Minnesota
city: Las Vegas
country: United States
facility: Mesoblast Investigational Site 13281
state: Nevada
city: Newark
country: United States
facility: Mesoblast Investigational Site 13263 - RWJ Barnabas Heart Center
state: New Jersey
city: New York
country: United States
facility: Mesoblast Investigational Site 10776 - Columbia University Medical Center
state: New York
city: Charlotte
country: United States
facility: Mesoblast Investigational Site 13026 - Sanger Heart and Vascular Institute, Carolinas Healthcare System
state: North Carolina
city: Durham
country: United States
facility: Mesoblast Investigational Site 10781 - Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Mesoblast Investigational Site 10758 - The Christ Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Mesoblast Investigational Site 10770 - University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Mesoblast Investigational Site 10773
state: Ohio
city: Columbus
country: United States
facility: Mesoblast Investigational Site 13278 - OhioHealth Research Institute
state: Ohio
city: Allentown
country: United States
facility: Mesoblast Investigational Site 10785 - Lehigh Valley Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Mesoblast Investigational Site 13261 - University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Mesoblast Investigational Site 10767 - Temple University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Mesoblast Investigational Site 13277
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Mesoblast Investigational Site 10774 - University of Pittsburgh
state: Pennsylvania
city: Germantown
country: United States
facility: Mesoblast Investigational Site 10777 - Stern Cardiovascular Foundation
state: Tennessee
city: Austin
country: United States
facility: Mesoblast Investigational Site 13024 - Austin Heart, PLLC
state: Texas
city: Dallas
country: United States
facility: Mesoblast Investigational Site 13274 - Soltero CV Research Center, Baylor Scott & White Research Institute
state: Texas
city: Houston
country: United States
facility: Mesoblast Investigational Site 10755 - Texas Heart Institute
state: Texas
city: Houston
country: United States
facility: Mesoblast Investigational Site 13268 - Houston Methodist Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Mesoblast Investigational Site 10763 - University Hospital
state: Utah
city: Seattle
country: United States
facility: Mesoblast Investigational Site 10771 - Heart & Vascular Research, Swedish Medical Center
state: Washington
city: Madison
country: United States
facility: Mesoblast Investigational Site 10764 - University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Mesoblast Investigational Site 10769 - Aurora Healthcare
state: Wisconsin
city: Milwaukee
country: United States
facility: Mesoblast Investigational Site 13279
state: Wisconsin
city: Wausau
country: United States
facility: Mesoblast Investigational Site 10789 - Aspirus Research Institute
state: Wisconsin
city: Edmonton
country: Canada
facility: Mesoblast Investigational Site 11027
state: Alberta
city: Victoria
country: Canada
facility: Mesoblast Investigational Site 11024 - Victoria Heart Institute Foundation
state: British Columbia
city: Toronto
country: Canada
facility: Mesoblast Investigational Site 11025 - St. Michael's Hospital
state: Ontario
Study officials:
affiliation: Mesoblast, Ltd.
name: Fred Grossman, DO
role: STUDY_DIRECTOR
References:
citation: Borow KM, Yaroshinsky A, Greenberg B, Perin EC. Phase 3 DREAM-HF Trial of Mesenchymal Precursor Cells in Chronic Heart Failure. Circ Res. 2019 Jul 19;125(3):265-281. doi: 10.1161/CIRCRESAHA.119.314951. Epub 2019 Jul 18.