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

NCT ID: NCT02467387

Last Updated: 2020-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-01
• Study Completion Date: 2017-05-11

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.

Conditions

Non-Ischemic Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Experimental: Human (aMBMC)

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.

Group Type: EXPERIMENTAL

Allogeneic Mesenchymal Bone Marrow Cells (aMBMC)

Intervention Type: DRUG

One time infusion Allogeneic Mesenchymal Bone Marrow Cells (aMBMC) 1.5 million cells/kg.

Placebo:Lactated Ringer's Solution (LRS)

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

Group Type: PLACEBO_COMPARATOR

Lactated Ringer's Solution

Intervention Type: DRUG

One time infusion 1.5mL/kg

Interventions

Allogeneic Mesenchymal Bone Marrow Cells (aMBMC)

One time infusion Allogeneic Mesenchymal Bone Marrow Cells (aMBMC) 1.5 million cells/kg.

Intervention Type: DRUG

Lactated Ringer's Solution

One time infusion 1.5mL/kg

Intervention Type: DRUG

Other Intervention Names

Mesenchymal Stem Cells, (MSC) Marrow Stromal Cells.; (LRS)

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stemedica Cell Technologies, Inc.

INDUSTRY

Sponsor Role: collaborator

CardioCell LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kristrun Stardal, RN, BSN

Role: STUDY_DIRECTOR

Clinical Operations Manager

Locations

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Emory University Hospital

Atlanta, Georgia, United States

Northwestern University Centers for Heart Failure Therapy

Chicago, Illinois, United States

Stony Brook Heart Institute

Stony Brook, New York, United States

Hospital of the University of Pennsylvania, Heart Failure and Transplant Program

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27856497 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

STEM-104-M-CHF

Identifier Type: -

Identifier Source: org_study_id

NCT02123706

Identifier Type: -

Identifier Source: nct_alias