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Efficacy and Safety of Allogeneic Mesenchymal Precursor Cells (Rexlemestrocel-L) for the Treatment of Heart Failure. (DREAM HF-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02032004
Recruitment Status : Active, not recruiting
First Posted : January 9, 2014
Last Update Posted : April 5, 2019
Sponsor:
Information provided by (Responsible Party):
Mesoblast, Ltd. ( Mesoblast, Inc. )

Tracking Information
First Submitted Date  ICMJE January 8, 2014
First Posted Date  ICMJE January 9, 2014
Last Update Posted Date April 5, 2019
Actual Study Start Date  ICMJE January 2014
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 2, 2019)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 8, 2014)
Time to first heart failure (HF)-related major adverse cardiac events (HF-MACE) [ Time Frame: 5 Years ]
Change History Complete list of historical versions of study NCT02032004 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2019)
  • 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 ]
  • 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 LVEF (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 - 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, WBC, eosinophils, ANC, platelet 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 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 - QTcF, QTcB, QT, 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2014)
  • Total hospital admissions for HF [ Time Frame: 5 Years ]
  • Length of in-hospital stay for HF [ Time Frame: 5 years ]
  • Cardiac survival [ Time Frame: 5 Years ]
  • Overall survival (captures all cause deaths) [ Time Frame: 5 years ]
  • Time-to-death from cardiovascular causes [ Time Frame: 5 years ]
  • Change from baseline in 2-D echocardiography [ Time Frame: Baseline, months 3, 6, 12, 24, 36, 48, and 60 ]
  • Change from baseline in exercise capacity during the 6-minute walk test (6MWT) [ Time Frame: Baseline, months 3, 6, 12, 24, 36, 48, and 60 ]
    Assessed by change from baseline in distance covered
  • Change in New York Heart Association (NYHA) functional class [ Time Frame: Baseline, months 3, 6, 12, 24, 36, 48, and 60 ]
    Functional status as assessed by observation and examination by the investigator
  • Change from baseline in the Minnesota Living With Heart Failure (MLHF) questionnaire score [ Time Frame: Baseline and months 3, 6, 12, 24, 36, 48, and 60 ]
    The MLHF questionnaire evaluates a total of 21 facets in questions using a scale ranging from 0 to 5, with 0 indicating 'No', 1 'Very Little' and 5 'Very Much' impact.
  • Change from Baseline in Quality of Life (QoL) EuroQoL 5-dimensional (EQ-5D) questionnaire score [ Time Frame: Baseline, months 3, 6, 12, 24, 36, 48, and 60 ]
    A self-administered, subjective QoL questionnaire with 0 meaning Worst health and 100 meaning best health.
  • Summary of participants with adverse events [ Time Frame: 5 Years ]
Current Other Pre-specified Outcome Measures
 (submitted: April 2, 2019)
  • Pharmacodynamics Measures (NT-proBNP and hsCRP) [ Time Frame: Screening, months 3, 6, 12 and every 12 months thereafter until study conclusion ]
  • Pharmacogenomics (PGx) Analysis [ Time Frame: Screening (only from those subjects who provide consent to participate in PGx sample collection) ]
  • Immunogenicity Measures (panel reactive antibodies, donor specific antibody, if PRA test is positive, antibodies against bovine and murine products) [ Time Frame: Screening, day 10, months 1, 3, 6, and 12 ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Allogeneic Mesenchymal Precursor Cells (Rexlemestrocel-L) for the Treatment of Heart Failure.
Official Title  ICMJE 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
Brief Summary The primary objective of this study is to determine whether transendocardial delivery of allogeneic human bone marrow-derived MPCs (rexlemestrocel-L) is effective in the treatment of chronic heart failure due to 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 (HF-MACE), preventing further adverse cardiac remodeling (LVESV and LVEDV), and increasing exercise capacity (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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Chronic Heart Failure
Intervention  ICMJE
  • Biological: Allogeneic Mesenchymal Precursor Cells (MPC)
    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 Names:
    • MPC
    • rexlemestrocel-L
  • Other: Sham Comparator
    The sham procedure will be staged to script and will not include actual cardiac mapping or delivery of rexlemestrocel-L.
Study Arms  ICMJE
  • Experimental: Allogeneic Mesenchymal Precursor Cells
    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.
    Intervention: Biological: Allogeneic Mesenchymal Precursor Cells (MPC)
  • Sham Comparator: Control Treatment
    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.
    Intervention: Other: Sham Comparator
Publications * 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. Erratum in: Circ Res. 2019 Aug 16;125(5):e28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 2, 2019)
566
Original Estimated Enrollment  ICMJE
 (submitted: January 8, 2014)
1730
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries Austria,   Belarus,   Bulgaria,   Finland,   France,   Germany,   Italy,   Latvia,   Lithuania,   Netherlands,   Poland,   Russian Federation,   Singapore,   Slovenia,   Spain,   Sweden,   Switzerland,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT02032004
Other Study ID Numbers  ICMJE MSB-MPC-CHF001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Mesoblast, Ltd. ( Mesoblast, Inc. )
Study Sponsor  ICMJE Mesoblast, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Donna Skerrett, MD Mesoblast, Ltd.
PRS Account Mesoblast, Ltd.
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP