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

• Sponsor: Mesoblast, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02032004
• Collaborator: (none)
• Enrollment: 566
• Locations: 59
• Arms: 2
• Actual Duration (Months): 75.4
• Patients Per Site: 9.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Heart Failure	Biological: Allogeneic Mesenchymal Precursor Cells (MPCs); Other: Sham Comparator	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 566 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 14, 2014
• Actual Primary Completion Date: May 29, 2020
• Actual Study Completion Date: May 29, 2020

Arms and Interventions

Arm	Intervention/Treatment
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.	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 Names: MPCs rexlemestrocel-L
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.	Other: Sham Comparator; The sham procedure will be staged to script and will not include actual cardiac mapping or delivery of rexlemestrocel-L.

Outcome Measures

Primary Outcome Measures

1. 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

1. Time-to-first terminal cardiac event (TCE) [6 Month minimum]

2. Time-to-hospital admissions for non-fatal decompensated HF events [6 Month minimum]

3. Time-to-urgent care outpatient HF visits [6 Month minimum]

4. Time-to-successfully resuscitated cardiac death (RCD) events [6 Month minimum]

5. Total length of in-hospital stay in intensive care unit for non-fatal decompensated HF events [6 Month minimum]

6. Time-to-first HF-MACE (composite of hospital admissions for decompensated HF, urgent care outpatient HF visit, and successfully RCD events) [6 Month minimum]

7. 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]

8. Time-to-cardiac death [6 Month minimum]

9. Time-to-all-cause death [6 Month minimum]

10. Time-to-first non-fatal MI (myocardial infarction), non-fatal CVA (cerebrovascular attack) or coronary artery revascularization [6 Month minimum]

11. 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)]

12. Correlations between baseline LVESV <=100 mL and LVESV >100 mL and clinical outcomes [6 Month minimum]

13. Correlations between baseline LVESV <=100 mL and LVESV >100 mL and change in Month 6 to baseline LVESV and clinical outcomes [6 Month minimum]

14. 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)]

15. 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)]

16. 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)]

17. 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)]

18. 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)]

19. 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)]

20. 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]

21. Safety as assessed by occurrence of treatment-emergent adverse events [Screening through 6 Month minimum]

22. 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) [Screening, day 0 (post-procedure), day 10, months 1, 3, 6, and 12, and every 6 months thereafter during study conduct (6 Month minimum)]

    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)

23. 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)]

24. 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)]

25. 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)]

26. Safety as assessed by telemetry monitoring findings (clinically significant arrhythmias) [Day 0 through Day 0 overnight post-procedure]

27. 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)]

28. 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]

29. 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)]

30. Safety as assessed by important cardiovascular events from adjudicated data [6 Month minimum]

Other Outcome Measures

1. 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]

2. Pharmacogenomics (PGx) Analysis [Screening (only from those subjects who provide consent to participate in PGx sample collection)]

3. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mesoblast Investigational Site 10757 - Cardiology, P.C.	Birmingham	Alabama	United States	35211
2	Mesoblast Investigational Site 13262 - University of Alabama at Birmingham Hospital	Birmingham	Alabama	United States	35233
3	Mesoblast Investigational Site 10779 - Mercy Gilbert Medical Center	Gilbert	Arizona	United States	85297
4	Mesoblast Investigational Site 10786 - Cardiovascular Associates of Mesa	Mesa	Arizona	United States	85206
5	Mesoblast Investigational Site 10756 - Mayo Clinic	Phoenix	Arizona	United States	85054
6	Mesoblast Investigational Site 13023 - University of Arizona Medical Center	Tucson	Arizona	United States	85724
7	Mesoblast Investigational Site 10754 - University of California, San Diego	La Jolla	California	United States	92037
8	Mesoblast Investigational Site 10759 - Scripps Clinic	La Jolla	California	United States	92037
9	Mesoblast Investigational Site 13265 - University of California, Los Angeles	Los Angeles	California	United States	90045
10	Mesoblast Investigational Site 10775 - Cedars-Sinai Medical Care Foundation	Los Angeles	California	United States	90211
11	Mesoblast Investigational Site 10778 - Orange County Cardiology	Orange	California	United States	92868
12	Mesoblast Investigational Site 13031 - St. John's Regional Medical Center	Oxnard	California	United States	93030
13	Mesoblast Investigational Site 13275 - Stanford University Hospital	Stanford	California	United States	94305
14	Mesoblast Investigational Site 13267 - Bethesda Heart Hospital	Boynton Beach	Florida	United States	33435
15	Mesoblast Investigational Site 10780 - Morton Plant Hospital	Clearwater	Florida	United States	33756
16	Mesoblast Investigational Site 10760 - Shands Hospital, University of Florida	Gainesville	Florida	United States	32610
17	Mesoblast Investigational Site 13273 - University of Florida Health	Jacksonville	Florida	United States	32209
18	Mesoblast Investigational Site 10768 - University of Miami	Miami	Florida	United States	33215
19	Mesoblast Investigational Site 13280	Orlando	Florida	United States
20	Mesoblast Investigational Site 13264 - Florida Hospital Pepin Heart Institute	Tampa	Florida	United States	33613
21	Mesoblast Investigational Site 13027 - Emory University School of Medicine	Atlanta	Georgia	United States	30322
22	Mesoblast Investigational Site 10765 - Georgia Regents University	Augusta	Georgia	United States	30912
23	Mesoblast Investigational Site 10772 - University Cardiologist, Rush University Medical Center	Chicago	Illinois	United States	60612
24	Mesoblast Investigational Site 13030 - University of Iowa	Iowa City	Iowa	United States	52242
25	Mesoblast Investigational Site 10783 - Gill Heart Institute, University of Kentucky	Lexington	Kentucky	United States	40536
26	Mesoblast Investigational Site 13022 - University of Louisville	Louisville	Kentucky	United States	40202
27	Mesoblast Investigational Site 13266	New Orleans	Louisiana	United States
28	Mesoblast Investigational Site 10782	Boston	Massachusetts	United States
29	Mesoblast Investigational Site 10766 - Michigan Cardiovascular Institute	Saginaw	Michigan	United States	48602
30	Mesoblast Investigational Site 10762 - Minneapolis Heart Institute	Minneapolis	Minnesota	United States	55407
31	Mesoblast Investigational Site 10761 - Mayo Clinic	Rochester	Minnesota	United States	55905
32	Mesoblast Investigational Site 13281	Las Vegas	Nevada	United States
33	Mesoblast Investigational Site 13263 - RWJ Barnabas Heart Center	Newark	New Jersey	United States	07112
34	Mesoblast Investigational Site 10776 - Columbia University Medical Center	New York	New York	United States	10032
35	Mesoblast Investigational Site 13026 - Sanger Heart and Vascular Institute, Carolinas Healthcare System	Charlotte	North Carolina	United States	28203
36	Mesoblast Investigational Site 10781 - Duke University	Durham	North Carolina	United States	27710
37	Mesoblast Investigational Site 10758 - The Christ Hospital	Cincinnati	Ohio	United States	45219
38	Mesoblast Investigational Site 10770 - University of Cincinnati	Cincinnati	Ohio	United States	45267
39	Mesoblast Investigational Site 10773	Cleveland	Ohio	United States
40	Mesoblast Investigational Site 13278 - OhioHealth Research Institute	Columbus	Ohio	United States	43214
41	Mesoblast Investigational Site 10785 - Lehigh Valley Hospital	Allentown	Pennsylvania	United States	18103
42	Mesoblast Investigational Site 13261 - University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
43	Mesoblast Investigational Site 10767 - Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
44	Mesoblast Investigational Site 13277	Philadelphia	Pennsylvania	United States
45	Mesoblast Investigational Site 10774 - University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
46	Mesoblast Investigational Site 10777 - Stern Cardiovascular Foundation	Germantown	Tennessee	United States	38125
47	Mesoblast Investigational Site 13024 - Austin Heart, PLLC	Austin	Texas	United States	78756
48	Mesoblast Investigational Site 13274 - Soltero CV Research Center, Baylor Scott & White Research Institute	Dallas	Texas	United States	75226
49	Mesoblast Investigational Site 10755 - Texas Heart Institute	Houston	Texas	United States	77030
50	Mesoblast Investigational Site 13268 - Houston Methodist Hospital	Houston	Texas	United States	77030
51	Mesoblast Investigational Site 10763 - University Hospital	Salt Lake City	Utah	United States	84132
52	Mesoblast Investigational Site 10771 - Heart & Vascular Research, Swedish Medical Center	Seattle	Washington	United States	98122
53	Mesoblast Investigational Site 10764 - University of Wisconsin	Madison	Wisconsin	United States	53792
54	Mesoblast Investigational Site 10769 - Aurora Healthcare	Milwaukee	Wisconsin	United States	53215
55	Mesoblast Investigational Site 13279	Milwaukee	Wisconsin	United States
56	Mesoblast Investigational Site 10789 - Aspirus Research Institute	Wausau	Wisconsin	United States	54401
57	Mesoblast Investigational Site 11027	Edmonton	Alberta	Canada
58	Mesoblast Investigational Site 11024 - Victoria Heart Institute Foundation	Victoria	British Columbia	Canada	V8R 4R2
59	Mesoblast Investigational Site 11025 - St. Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8

Sponsors and Collaborators

• Mesoblast, Inc.

Investigators

• Study Director: Fred Grossman, DO, Mesoblast, Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mesoblast, Inc.
• ClinicalTrials.gov Identifier: NCT02032004
• Other Study ID Numbers: MSB-MPC-CHF001
• First Posted: Jan 9, 2014
• Last Update Posted: Jan 10, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Mesoblast, Inc.: Chronic Heart Failure; CHF; Left Ventricular Systolic Dysfunction; Ischemic Heart Failure; Nonischemic Heart Failure; Stem Cells; Allogeneic Mesenchymal Precursor Cells
• Additional relevant MeSH terms: Heart Failure

Study Results

No Results Posted as of Jan 10, 2022