Clinical trial NCT04476901: Administration of Allogeneic-MSC in Patients with Non-Ischemic Dilated Cardiomyopathy
Official title: A Phase IIB Randomized, Placebo-Controlled, Multicenter Study of the Comparative Efficacy and Safety of Administration of Allogeneic-MSC Versus Placebo in Patients with Non- Ischemic Dilated Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-ischemic Dilated Cardiomyopathy
Keywords: Allogeneic mesenchymal stem cells
Bone marrow-derived mesenchymal stem cells
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: The University of Texas Health Science Center, Houston
First posted: 2020-07-20
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and effectiveness of an experimental drug called human allogeneic mesenchymal stem cell therapy.


Eligibility criteria: Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Men and women aged 18 to 80 years (inclusive) at the time of signing the informed consent form.
2. Diagnosis of NIDCM with left ventricular ejection fraction ≤45%.
3. Appropriate guideline-directed optimal medical therapy for non-ischemic cardiomyopathy. At a minimum, subjects must be on beta blockers and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) or Angiotensin Receptor Neprilysin Inhibitors (ARNI) or have appropriate medical indication precluding use of one or both of these agents. Subjects must be on a stable regimen for at least 30 days prior to the procedure. Dose titration is allowed.
4. Be a candidate for cardiac catheterization\*
5. Be willing to undergo DNA test.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Be eligible for or require standard-of-care surgical or percutaneous intervention for the treatment of non-ischemic dilated cardiomyopathy
2. Clinical manifestation of coronary artery disease (CAD) (e.g., chest pain and concomitant clinical findings such as electrocardiogram changes suggestive of coronary ischemia, myocardial infarction) or evidence of endocardial or transmural scar on cardiac MRI suggestive of undiagnosed CAD or history of percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Be indicated for or require coronary artery revascularization
3. Documented presence of epicardial stenosis of 70% or greater in one or more major epicardial coronary arteries
4. Valvular heart disease including 1) aortic valve prosthesis, mechanical mitral valve, and mitral valve clip; 2) severe aortic valve insufficiency/regurgitation within 12 months of consent\*
5. Aortic stenosis with valve area ≤ 1.5cm2\*
6. Cardiomyopathy due to acute Post-partum (within 6 months), Non-compaction\*, or Hypertrophic\* cardiomyopathy
7. Cardiomyopathy due to known toxin (e.g amyloid) Note: anthracycline induced cardiomyopathy will be allowed
8. QTc interval \> 550 ms on baseline electrocardiogram (ECG) (note: QTc interval is the interval between the start of the Q wave and the end of the T wave in the heart's electrical cycle)
9. Automated Implantable Cardioverter Defibrillator (AICD) appropriate firing or anti tachycardia pacing for ventricular tachycardia or ventricular fibrillation within 30 days prior to consent
10. Have an estimated baseline glomerular filtration rate below the clinical site's institutional cutoff
11. A hematologic abnormality during baseline testing as evidenced by hemoglobin \< 9 g/dl; hematocrit \< 30%; absolute neutrophil count \< 2,000 or total WBC count more than 2 times upper limit of normal; or platelet values \< 100,000/ul
12. Have liver dysfunction, as evidenced by enzymes Aspartate Transaminase Enzyme (AST) and Alanine Aminotransferase Enzyme (ALT) greater than three times the ULN
13. Have a bleeding diathesis or coagulopathy (International Normalised Ratio (INR) \> 1.5), cannot be withdrawn from anticoagulation therapy, or will refuse blood transfusions
14. Be a solid organ transplant recipient. This does not include prior cell based therapy (\>12 months prior to enrollment), bone, skin, ligament, tendon or corneal grafting.
15. Have a history of organ or cell transplant rejection
16. Have a clinical history of malignancy within the past 12 months (i.e., subjects with prior malignancy must be disease free for 12 months), except curatively treated basal cell or squamous cell carcinoma or cervical carcinoma
17. Drug and/or alcohol abuse or dependence within the past 9 months
18. Be serum positive for HIV, hepatitis B surface antigen, or viremic hepatitis C
19. Documented presence of a known Left Ventricular (LV) thrombus, aortic dissection, or aortic aneurysm. (Refer to "Guidance to the PI" section with regards to LV thrombus, below)\*
20. Blood glucose levels (HbA1c) \>10%
21. Severe radiographic contrast allergy
22. Known history of anaphylactic reaction to penicillin or streptomycin
23. Hypersensitivity to dimethyl sulfoxide (DMSO)
24. Non-cardiac condition with life expectancy \< 1 year
25. Acute stroke or transient ischemic attack within 3 months of enrollment
26. Be pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods
27. Pacemaker-dependence with an Implantable Cardioverter Defibrillator (ICD) (Note: pacemaker-dependent candidates without an ICD are not excluded)
28. Presence of a pacemaker and/or ICD generator with any of the following limitations/conditions:

    * manufactured before the year 2000
    * leads implanted \< 6 weeks prior to consent
    * non-transvenous epicardial or abandoned leads
    * subcutaneous ICDs
    * leadless pacemakers
29. A cardiac resynchronization therapy (CRT) device implanted less than 3 months prior to consent
30. Other MRI contraindications (e.g. subject body habitus incompatible with MRI)
31. Need for advanced heart failure therapy (e.g. IV inotropes)
32. Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial
33. Any other condition that in the judgment of the Investigator would be a contraindication to enrollment or follow-up

(\*) Applies to subjects receiving product via transendocardial administration only

Primary outcomes:
measure: Change in LVEF
timeFrame: Baseline, 12 months
Secondary outcomes:
measure: Change in global ventricular strain
timeFrame: Baseline, 12 months
measure: Change in left regional strain
timeFrame: Baseline, 12 months
measure: Left ventricular function concordance
timeFrame: 12 months
measure: Change in LVEDVI
timeFrame: Baseline, 12 months
measure: Change in LVESVI
timeFrame: Baseline, 12 months
measure: Change in Maximal oxygen consumption (peak VO2)
timeFrame: Baseline, 12 months
measure: Change in Exercise tolerance
timeFrame: Baseline, 12 months
measure: Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) Score
timeFrame: Baseline, 12 months
measure: Change in New York Heart Association (NYHA) Class
timeFrame: Baseline, 12 months
measure: Percent change in flow mediated diameter
timeFrame: Baseline, 12 months
measure: Change in EPC-CFU
timeFrame: Baseline, 12 months
measure: Change in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP)
timeFrame: Baseline, 12 months
measure: Change in cytokines
timeFrame: Baseline, 12 months
measure: Incidence of MACE
timeFrame: 12 months
measure: Incidence of TE-SAEs
timeFrame: Day 30
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Houston
country: United States
facility: Texas Heart Institute
state: Texas
Study officials:
affiliation: University of Miami
name: Joshua Hare, MD
role: PRINCIPAL_INVESTIGATOR
References: