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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Chronic Heart Failure

Intervention / Treatment
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* Biological: Allogeneic Mesenchymal Precursor Cells (MPCs)
* Other: Sham Comparator


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogeneic Mesenchymal Precursor Cells<br>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. | Biological: Allogeneic Mesenchymal Precursor Cells (MPCs)<br>* 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<br>* Other names: rexlemestrocel-L;|
| Sham Comparator: Control Treatment<br>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. | Other: Sham Comparator<br>* The sham procedure will be staged to script and will not include actual cardiac mapping or delivery of rexlemestrocel-L.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-first terminal cardiac event (TCE) |  | 6 Month minimum | 
| Time-to-hospital admissions for non-fatal decompensated HF events |  | 6 Month minimum | 
| Time-to-urgent care outpatient HF visits |  | 6 Month minimum | 
| Time-to-successfully resuscitated cardiac death (RCD) events |  | 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-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-first non-fatal MI (myocardial infarction), non-fatal CVA (cerebrovascular attack) or coronary artery revascularization |  | 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 | 
| Correlations between baseline LVESV <=100 mL and LVESV >100 mL and change in Month 6 to baseline LVESV and clinical outcomes |  | 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) | 
| 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) | 
| 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 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 occurrence of treatment-emergent adverse events |  | 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) | 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) |  | 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) | 
| 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 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 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 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) | 
| Safety as assessed by important cardiovascular events from adjudicated data |  | 6 Month minimum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allogeneic Mesenchymal Precursor Cells, CHF, Chronic Heart Failure, Left Ventricular Systolic Dysfunction, Ischemic Heart Failure, Nonischemic Heart Failure, Stem Cells