Clinical Trials

Chronic Heart Failure

CardioCell is making significant progress in clinical trials for its indication for chronic heart failure (HF). Chronic HF represents single largest cause of natural death in the United States. Approximately 5.5 million individuals suffer from chronic HF, and it generates more than 1 million hospitalizations annually, with a striking 50-percent mortality and re-admission rate after 60-90 days post-discharge1.

Based on the scope and severity of this condition, CardioCell enlisted prominent cardiologists Drs. Mihai Gheorghiade and Javed Butler to its Scientific Advisory Board to create a strategic chronic HF program to accelerate therapies from the research bench to the bedside. In collaboration with other renowned cardiologists, CardioCell has launched the first initiative in its chronic HF program – the first Phase IIa clinical trial using intravenous (IV) delivery of its itMSCs to address dilated chronic HF.

Results of the study “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,” were presented at a “Hot Line” Late-Breaking Session at the European Society of Cardiology (ESC) Congress 2016. Dr. Javed Butler, Chief of the Cardiology Division and Co-Director of the Heart Institute at Stony Brook University shared these slides:

Results Highlights

  • The study protocol tests safety and capacity of CardioCell’s ischemia-tolerant MSCs (itMSCs) to exert beneficial effects via IV administration. Data show statistically significant improvement in 6-minute walk test, quality of life scores and classifications — as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ) and New York Heart Association (NYHA) — and favorable immune modulatory benefits. Observations include:
  • An IV injection strategy is safe and well-tolerated. There are no major differences in any of the safety endpoints, including clinical events like all-cause mortality, all-cause hospitalization and adverse events, and there are no alterations in pulmonary function, liver function or arrhythmias.
  • IV itMSC injections exhibit improvements in several clinical-efficacy endpoint measurements.
    Intravenously administered itMSCs suppress inflammation, which is noteworthy because inflammation is believed to importantly contribute to HF progression. There was a statistically significant reduction in natural killer (NK) cells, the magnitude of which correlated with the magnitude of improvement in left ventricular ejection fraction.
  • Three months after the injection, the experimental group showed statistically significant improvement in left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV) — measured by MRI — while there was no statistically significant change in the placebo group. This data suggests reversal of adverse remodeling.

Study Details:

  • Type: Phase IIa, single-blind, placebo-controlled, crossover study
  • Sites: Emory University, Northwestern University, Stony Brook University and the University of Pennsylvania
  • Patients: 22 participants with non-ischemic cardiomyopathy and LVEF ≤40%
  • Structure: The study randomized patients into a treatment group and a control group with a 1:1 randomization scheme. After 90 days there was cross-over administration, where placebo group received cells, while initial experimental group received placebo. CardioCell’s treatment and the placebo were administered intravenously.
  • Measurements: Progress was tracked at the baseline, at 90 days and at 180 days and was measured by the KCCQ, 6-minute walk, NYHA and cardiac MRI. At Duke University’s cardiac imaging core laboratory, the MRI images were analyzed by Dr. Raymond Kim, professor of medicine and radiology at Duke University Medical Center and founder and co-director of the Duke Cardiovascular Magnetic Resonance Center.
  • Authors: Javed Butler, M.D., MPH, MBA; Stephen E. Epstein M.D.; Stephen J. Greene M.D.; Arshed A. Quyyumi M.D.; Sergey Sikora Ph.D.; Raymond J. Kim M.D., Ph.D.; Allen S. Anderson M.D.; Jane E. Wilcox M.D.; Nikolai I. Tankovich M.D.; Michael J. Lipinski M.D.; Kenneth B. Margulies M.D.; Robert T. Cole M.D.; Hal A. Skopicki M.D., Ph.D.; and Mihai Gheorghiade M.D.

Results were published in Circulation Research

  1. Butler J, Fonarow GC, et al. Strategies and Opportunities for Drug Development in Heart Failure. JAMA 2013: E1-E2.