Clinical trial NCT02467387: A Study to Assess the Effect of Intravenous Dose of (aMBMC) to Subjects With Non-ischemic Heart Failure
Official title: A Phase IIa Randomized Study to Assess the Safety, Tolerability, and Preliminary Efficacy of a Single Intravenous Dose of Ischemia-tolerant Allogeneic Mesenchymal Bone Marrow Cells to Subjects With Non-ischemic Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Ischemic Heart Failure
Keywords: Non-ischemic Heart Failure
Stem Cells
Lead sponsor: CardioCell LLC
Sponsor class: INDUSTRY
Collaborators: name: Stemedica Cell Technologies, Inc.
First posted: 2015-06-10
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: A phase IIa study to assess the safety and preliminary efficacy of intravenous dose of ischemia-tolerant Allogeneic Mesenchymal Bone Marrow Cells in subjects with non-ischemic heart failure.

Detailed description: A phase IIa, single-blind, placebo-controlled, crossover, multi-center, randomized study to assess the safety, tolerability, and preliminary efficacy of a single intravenous dose of ischemia-tolerant allogeneic mesenchymal bone marrow cells to subjects with heart failure of non-ischemic etiology.

Eligibility criteria: Inclusion Criteria:

1. Males and females ≥18 years of age
2. LVEF ≤35% on echocardiogram within 12 months of randomization to undergo MRI
3. Screening cardiac MRI at baseline with:

   Ejection fraction ≤40% No significant hyper enhancement on MRI scan in the opinion of the central imaging lab reviewer
4. Patients with non-ischemic heart failure etiology, as documented by absent or non-obstructive coronary artery disease on x-ray angiography or coronary computed tomography
5. Patients with history of heart failure and treated for at least three months with GDMT
6. NYHA class II-III symptoms
7. Ability to understand and provide signed informed consent
8. Reasonable expectation that patient will receive standard post-treatment care and attend all scheduled safety follow-up visits

Exclusion Criteria:

1. Pregnant or nursing women or those of childbearing age and not using an effective method of contraception
2. History of stroke within 3 months
3. Cardiac surgery within 3 months prior to randomization or the likelihood of a requirement for such procedures during the study period
4. Current ICD or CRT or implantation planned within 6 months of infusion
5. Presence of clinically significant, uncorrected valvular heart disease, hypertrophic or restrictive cardiomyopathy, active myocarditis, or uncontrolled hypertension
6. History of cardiac arrest or life-threatening arrhythmias within 3 months
7. Treatment with parenteral inotropic agents within 1 month of randomization
8. Anticipated cardiac transplantation within 1 year
9. Illness other than heart failure with life expectancy less than 1 year
10. Received an experimental drug or device within 30 days of randomization
11. Left ventricular assist device or implantation planned in the next 6 months
12. Patients with complex congenital heart disease
13. Uncontrolled seizure disorder
14. Presence of immune deficiency
15. Clinically significant hematologic, hepatic, or renal impairment as determined by screening clinical laboratory tests:

    * Liver disease = ALT or AST \> 3x normal, alkaline phosphatase or bilirubin \>2x normal)
    * Renal disease = estimated glomerular filtration rate as assessed by the MDRD formula \<30 ml/min
    * Hematologic = Unexplained leukocytosis \>10 or hemoglobin \< 9gm/dl
16. Presence of any other clinically-significant medical condition, psychiatric condition, or laboratory abnormality, that in the judgment of the investigator or sponsor for which participation in the study would pose a safety risk to the subject
17. Inability to comply with the conditions of the protocol
18. Malignancy within the previous five years, except adequately treated basal cell carcinoma, provided that it is neither infiltrating nor sclerosing, and carcinoma in situ of the cervix
19. Active myocarditis or early postpartum cardiomyopathy (within six months).
20. Systemic corticosteroids, cytostatics, immunosuppressive drug therapy (cyclophosphamide, methotrexate, cyclosporine, azathioprine, etc.), and DNA depleting or cytotoxic drugs taken within four weeks prior to study treatment
21. Porphyria
22. Allergy to sodium citrate or any "caine" type of local anesthetic
23. Any contraindication for gadolinium use for MRI
24. Patient scheduled for hospice care
25. Clinically relevant abnormal findings in the clinical history, physical examination, ECG, or laboratory tests at the screening assessment that would interfere with the objectives of the study or would preclude safe completion of the study. Abnormal findings could include: known HIV infection or other immunodeficiency state, chronic active viral infection (such as hepatitis B or C), acute systemic infections (defined as patients undergoing treatment with antibiotics), gastrointestinal tract bleeding, or any severe or acute concomitant illness or injury
26. Any other medical, social, or geographical factor that would make it unlikely that the patient could comply with study procedures (e.g., alcohol abuse, lack of permanent residence, severe depression, disorientation, distant location, or noncompliance)

Primary outcomes:
measure: Safety Will be Evaluated by Number of AE
timeFrame: Total AEs and SAEs within 450 days post-infusion
Secondary outcomes:
measure: Change in LVEF From Baseline to Day 90 Post-initial Infusion.
timeFrame: Baseline to Day 90
Other outcomes:
Locations:
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Centers for Heart Failure Therapy
state: Illinois
city: Stony Brook
country: United States
facility: Stony Brook Heart Institute
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania, Heart Failure and Transplant Program
state: Pennsylvania
Study officials:
affiliation: Clinical Operations Manager
name: Kristrun Stardal, RN, BSN
role: STUDY_DIRECTOR
References:
citation: Butler J, Epstein SE, Greene SJ, Quyyumi AA, Sikora S, Kim RJ, Anderson AS, Wilcox JE, Tankovich NI, Lipinski MJ, Ko YA, Margulies KB, Cole RT, Skopicki HA, Gheorghiade M. Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial. Circ Res. 2017 Jan 20;120(2):332-340. doi: 10.1161/CIRCRESAHA.116.309717. Epub 2016 Nov 16.