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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02467387
Recruitment Status : Completed
First Posted : June 10, 2015
Results First Posted : January 7, 2020
Last Update Posted : January 7, 2020
Sponsor:
Collaborator:
Stemedica Cell Technologies, Inc.
Information provided by (Responsible Party):
CardioCell LLC

Tracking Information
First Submitted Date  ICMJE June 2, 2015
First Posted Date  ICMJE June 10, 2015
Results First Submitted Date  ICMJE October 25, 2019
Results First Posted Date  ICMJE January 7, 2020
Last Update Posted Date January 7, 2020
Actual Study Start Date  ICMJE June 1, 2014
Actual Primary Completion Date May 11, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 6, 2020)
Safety Will be Evaluated by Number of AE [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: June 9, 2015)
Safety will be evaluated by the incidence, severity, and relationship of AEs and SAEs [ Time Frame: Change from Baseline, days 30, 60, 90, days 270 and 450 post initial infusion ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2020)
Change in LVEF From Baseline to Day 90 Post-initial Infusion. [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2015)
Change in LVEF from baseline to day 90 post-initial infusion. After crossover phase all subjects will be evaluated for changes from the new baseline (Day 90 after initial infusion) to Day 90 post second infusion. [ Time Frame: Baseline to Day 90 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess the Effect of Intravenous Dose of (aMBMC) to Subjects With Non-ischemic Heart Failure
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Non-Ischemic Heart Failure
Intervention  ICMJE
  • Drug: Allogeneic Mesenchymal Bone Marrow Cells (aMBMC)
    One time infusion Allogeneic Mesenchymal Bone Marrow Cells (aMBMC) 1.5 million cells/kg.
    Other Name: Mesenchymal Stem Cells, (MSC) Marrow Stromal Cells.
  • Drug: Lactated Ringer's Solution
    One time infusion 1.5mL/kg
    Other Name: (LRS)
Study Arms  ICMJE
  • Experimental: 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.
    Intervention: Drug: Allogeneic Mesenchymal Bone Marrow Cells (aMBMC)
  • Placebo Comparator: 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.
    Intervention: Drug: Lactated Ringer's Solution
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 19, 2016)
23
Original Estimated Enrollment  ICMJE
 (submitted: June 9, 2015)
20
Actual Study Completion Date  ICMJE May 11, 2017
Actual Primary Completion Date May 11, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02467387
Other Study ID Numbers  ICMJE STEM-104-M-CHF
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CardioCell LLC
Study Sponsor  ICMJE CardioCell LLC
Collaborators  ICMJE Stemedica Cell Technologies, Inc.
Investigators  ICMJE
Study Director: Kristrun Stardal, RN, BSN Clinical Operations Manager
PRS Account CardioCell LLC
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP