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

CardioCell

Status and phase: Completed; Phase 2

Conditions: Non-Ischemic Heart Failure

Treatments: Drug: Allogeneic Mesenchymal Bone Marrow Cells (aMBMC); Drug: Lactated Ringer's Solution

Study type: Interventional

Funder types: Industry

Identifiers

NCT02467387

STEM-104-M-CHF

Details and patient eligibility

About

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.

Full 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.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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23 participants in 2 patient groups, including a placebo group

Experimental: Human (aMBMC)

Experimental group

Description:

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.

Treatment:

Drug: Allogeneic Mesenchymal Bone Marrow Cells (aMBMC)

Placebo:Lactated Ringer's Solution (LRS)

Placebo Comparator group

Description:

Intervention: One time intravenous infusion of 1.5mL/kg Lactated Ringer's Solution (LRS) administered at a constant rate of approximately 2mL/min.

Treatment:

Drug: Lactated Ringer's Solution