A Study to Assess the Effect of Intravenous Dose of (aMBMC) to Subjects With Non-ischemic Heart Failure

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Non-Ischemic Heart Failure

Intervention / Treatment
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* Drug: Allogeneic Mesenchymal Bone Marrow Cells (aMBMC)
* Drug: Lactated Ringer's Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥18 years of age LVEF ≤35% on echocardiogram within 12 months of randomization to undergo MRI 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 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 Patients with history of heart failure and treated for at least three months with GDMT NYHA class II-III symptoms Ability to understand and provide signed informed consent Reasonable expectation that patient will receive standard post-treatment care and attend all scheduled safety follow-up visits Exclusion Criteria: Pregnant or nursing women or those of childbearing age and not using an effective method of contraception History of stroke within 3 months Cardiac surgery within 3 months prior to randomization or the likelihood of a requirement for such procedures during the study period Current ICD or CRT or implantation planned within 6 months of infusion Presence of clinically significant, uncorrected valvular heart disease, hypertrophic or restrictive cardiomyopathy, active myocarditis, or uncontrolled hypertension History of cardiac arrest or life-threatening arrhythmias within 3 months Treatment with parenteral inotropic agents within 1 month of randomization Anticipated cardiac transplantation within 1 year Illness other than heart failure with life expectancy less than 1 year Received an experimental drug or device within 30 days of randomization Left ventricular assist device or implantation planned in the next 6 months Patients with complex congenital heart disease Uncontrolled seizure disorder Presence of immune deficiency 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 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 Inability to comply with the conditions of the protocol 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 Active myocarditis or early postpartum cardiomyopathy (within six months). 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 Porphyria Allergy to sodium citrate or any caine type of local anesthetic Any contraindication for gadolinium use for MRI Patient scheduled for hospice care 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 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)

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Human (aMBMC)<br>Intervention: One time intravenous infusion of 1.5 million (aMBMC) per kg administered at approximately 2mL/min. Maximum dose as for 100kg subject or 150 million cells for any subject 100kg or more. | Drug: Allogeneic Mesenchymal Bone Marrow Cells (aMBMC)<br>* One time infusion Allogeneic Mesenchymal Bone Marrow Cells (aMBMC) 1.5 million cells/kg.<br>* Other names: Mesenchymal Stem Cells, (MSC) Marrow Stromal Cells.;|
| Placebo Comparator: Placebo:Lactated Ringer's Solution (LRS)<br>Intervention: One time intravenous infusion of 1.5mL/kg Lactated Ringer's Solution (LRS) administered at a constant rate of approximately 2mL/min. | Drug: Lactated Ringer's Solution<br>* One time infusion 1.5mL/kg<br>* Other names: (LRS);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Will be Evaluated by Number of AE | As identified in the SAP, the safety analysis was the primary objective and was evaluated by the number of AEs | Total AEs and SAEs within 450 days post-infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LVEF From Baseline to Day 90 Post-initial Infusion. | The secondary efficacy endpoint was the change in LVEF from baseline to Day 90 post-initial infusion. Participants with data available at each time point. | Baseline to Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-ischemic Heart Failure, Stem Cells