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

Chronic Heart Failure Clinical Trial

— DREAM HF-1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02032004
• Other study ID #: MSB-MPC-CHF001
• Status: Completed
• Phase: Phase 3
• Start date: February 14, 2014
• Est. completion date: May 29, 2020

Study information

• Verified date: January 2022
• Source: Mesoblast, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 566
• Est. completion date: May 29, 2020
• Est. primary completion date: May 29, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

Biological:
• Allogeneic Mesenchymal Precursor Cells (MPCs)
Rexlemestrocel-L consists of human bone marrow-derived allogeneic MPCs isolated from bone mononuclear cells with anti-STRO-3 antibodies, expanded ex vivo, and cryopreserved

Other:
• Sham Comparator
The sham procedure will be staged to script and will not include actual cardiac mapping or delivery of rexlemestrocel-L.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Mesoblast, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacodynamics Measures (N-terminal (NT)-pro hormone BNP [NT-proBNP] and high-sensitivity C-reactive protein [hs-CRP])		Screening, months 3, 6, 12 and every 12 months thereafter until study conclusion
Other	Pharmacogenomics (PGx) Analysis		Screening (only from those subjects who provide consent to participate in PGx sample collection)
Other	Immunogenicity Measures (panel reactive antibodies, donor specific antibody, if panel-reactive antibody (PRA) test is positive, antibodies against bovine and murine products)		Screening, day 10, months 1, 3, 6, and 12
Primary	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	Time-to-first terminal cardiac event (TCE)		6 Month minimum
Secondary	Time-to-hospital admissions for non-fatal decompensated HF events		6 Month minimum
Secondary	Time-to-urgent care outpatient HF visits		6 Month minimum
Secondary	Time-to-successfully resuscitated cardiac death (RCD) events		6 Month minimum
Secondary	Total length of in-hospital stay in intensive care unit for non-fatal decompensated HF events		6 Month minimum
Secondary	Time-to-first HF-MACE (composite of hospital admissions for decompensated HF, urgent care outpatient HF visit, and successfully RCD events)		6 Month minimum
Secondary	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
Secondary	Time-to-cardiac death		6 Month minimum
Secondary	Time-to-all-cause death		6 Month minimum
Secondary	Time-to-first non-fatal MI (myocardial infarction), non-fatal CVA (cerebrovascular attack) or coronary artery revascularization		6 Month minimum
Secondary	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)
Secondary	Correlations between baseline LVESV <=100 mL and LVESV >100 mL and clinical outcomes		6 Month minimum
Secondary	Correlations between baseline LVESV <=100 mL and LVESV >100 mL and change in Month 6 to baseline LVESV and clinical outcomes		6 Month minimum
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	Safety as assessed by occurrence of treatment-emergent adverse events		Screening through 6 Month minimum
Secondary	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)	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)	Screening, day 0 (post-procedure), day 10, months 1, 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Safety as assessed by telemetry monitoring findings (clinically significant arrhythmias)		Day 0 through Day 0 overnight post-procedure
Secondary	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)
Secondary	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
Secondary	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)
Secondary	Safety as assessed by important cardiovascular events from adjudicated data		6 Month minimum