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

Phase 2

Completed

• Conditions: Non-Ischemic Heart Failure
• Interventions: Drug: Allogeneic Mesenchymal Bone Marrow Cells (aMBMC); Drug: Lactated Ringer's Solution

• Registration Number: NCT02467387
• Lead Sponsor: CardioCell LLC

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.

Study Timeline

• Study Start: 2014-06-01
• Study First Submitted: 2015-06-02
• Study First Submitted QC: 2015-06-09
• Study First Posted: 2015-06-10
• Primary Completion: 2017-05-11
• Study Completion: 2017-05-11
• Results First Submitted: 2019-10-25
• Status Verified: 2019-12
• Results First Submitted QC: 2020-01-06
• Last Update Submitted: 2020-01-06
• Results First Posted: 2020-01-07
• Last Update Posted: 2020-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Experimental: Human (aMBMC)	Allogeneic Mesenchymal Bone Marrow Cells (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.
Placebo:Lactated Ringer's Solution (LRS)	Lactated Ringer's Solution	Intervention: One time intravenous infusion of 1.5mL/kg Lactated Ringer's Solution (LRS) administered at a constant rate of approximately 2mL/min.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in LVEF From Baseline to Day 90 Post-initial Infusion.	Baseline to Day 90	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.

Trial Locations

Locations (5)

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States

Northwestern University Centers for Heart Failure Therapy; 🇺🇸 Chicago, Illinois, United States

Hospital of the University of Pennsylvania, Heart Failure and Transplant Program; 🇺🇸 Philadelphia, Pennsylvania, United States

Stony Brook Heart Institute; 🇺🇸 Stony Brook, New York, United States

MedStar Washington Hospital Center; 🇺🇸 Washington, District of Columbia, United States