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

Phase 3CompletedNCT02032004

Mesoblast, Inc.566 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

566

Conditions

Chronic Heart Failure

Interventions

Allogeneic Mesenchymal Precursor Cells (MPCs)BIOLOGICAL

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

Sham ComparatorOTHER

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (59)

Outcomes

Primary Outcomes

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

Time frame: 6 Month minimum

Secondary Outcomes

Time-to-first terminal cardiac event (TCE)

Time frame: 6 Month minimum

Time-to-hospital admissions for non-fatal decompensated HF events

Time frame: 6 Month minimum

Time-to-urgent care outpatient HF visits

Time frame: 6 Month minimum

Time-to-successfully resuscitated cardiac death (RCD) events

Time frame: 6 Month minimum

Total length of in-hospital stay in intensive care unit for non-fatal decompensated HF events

Time frame: 6 Month minimum

Time-to-first HF-MACE (composite of hospital admissions for decompensated HF, urgent care outpatient HF visit, and successfully RCD events)

Time frame: 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)

Time frame: 6 Month minimum

Time-to-cardiac death

Time frame: 6 Month minimum

Time-to-all-cause death

Time frame: 6 Month minimum

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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 10779 - Mercy Gilbert Medical Center

Gilbert, Arizona, United States

Mesoblast Investigational Site 10786 - Cardiovascular Associates of Mesa

Mesa, Arizona, United States

Mesoblast Investigational Site 10756 - Mayo Clinic

Phoenix, Arizona, United States

Mesoblast Investigational Site 13023 - University of Arizona Medical Center

Tucson, Arizona, 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 13265 - University of California, Los Angeles

Los Angeles, California, United States

Mesoblast Investigational Site 10775 - Cedars-Sinai Medical Care Foundation

Los Angeles, California, United States

...and 49 more locations

Time-to-first non-fatal MI (myocardial infarction), non-fatal CVA (cerebrovascular attack) or coronary artery revascularization

Time frame: 6 Month minimum

Left Ventricular (LV) remodeling in LVESV determined by 2-D echocardiography

Time frame: 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

Time frame: 6 Month minimum

Correlations between baseline LVESV <=100 mL and LVESV >100 mL and change in Month 6 to baseline LVESV and clinical outcomes

Time frame: 6 Month minimum

LV remodeling in LVEDV determined by 2-D echocardiography

Time frame: 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])

Time frame: Screening, day 0 (post-procedure), months 3, 6, and 12, and every 12 months thereafter during study conduct (6 Month minimum)

Functional exercise capacity as assessed by 6 Minute Walk Test

Time frame: 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

Time frame: 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

Time frame: Screening, months 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)

Quality of Life Measure - European Quality of Life (EuroQoL) 5-dimensional (EQ-5D) questionnaire

Time frame: 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

Time frame: Day 0 through discharge from Day 0 hospitalization

Safety as assessed by occurrence of treatment-emergent adverse events

Time frame: Screening through 6 Month minimum

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)

Time frame: Screening, day 0 (post-procedure), day 10, months 1, 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)

Safety as assessed by urinalysis (blood, glucose, ketones, total protein)

Time frame: 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)

Time frame: 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 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.

Time frame: 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 telemetry monitoring findings (clinically significant arrhythmias)

Time frame: 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

Time frame: Day 10, months 1, 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)

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)

Time frame: Screening, day 0 (post-procedure), day 10, months 1 and 3

Safety as assessed by physical examination findings judged as clinically significant changes from baseline by the investigator or newly occurring abnormalities (including weight)

Time frame: 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)

Safety as assessed by important cardiovascular events from adjudicated data

Time frame: 6 Month minimum