Enrollment continues for first FDA-approved study involving multiple intravenous injections of mesenchymal stem cells for cardiovascular indications
SAN DIEGO—Sept. 27, 2019—CardioCell, a biotechnology company that uses allogeneic stem cells for cardiovascular indications, announces the treatment of its first patient in the MedStar Heart & Vascular Institute’s Phase IIa clinical trial that aims to determine whether patented, low-oxygen grown mesenchymal stem cells (itMSCs) improve myocardial function in patients with heart failure severe enough to require the implantation of a left ventricular assist device (LVAD). The study is still enrolling patients at the MedStar Washington Hospital Center.
The study, “A Randomized, Double-Blind, Placebo-Controlled Phase IIa Study of the Safety and Efficacy of Intravenous Delivery of Allogeneic Mesenchymal Stem Cells in Patients with Cardiomyopathy and Severe Heart Failure Who Required Implantation of a Left Ventricular Assist Device (LVAD),” aims to test if CardioCell’s therapy lowers persistent inflammation, a probable major cause of clinical and cardiac deterioration in LVAD patients. The trial advances research based on preclinical mouse studies demonstrating that the intravenous infusion of itMSCs diminished the excessive inflammatory responses present in mice with acute myocardial infarction and in mice with ischemic cardiomyopathy and, most importantly, markedly improved left ventricular function. Safety and promising signals of efficacy were also demonstrated in a trial in patients with stable chronic heart failure. The study, “Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial,” was published in Circulation Research in January 2017.
“MedStar Heart & Vascular Institute has one of the nation’s most advanced cardiology facilities, and we trust its expertise to validate our study results,” says Dr. Sergey Sikora, CardioCell’s president and CEO. “We hope our unique, low-oxygen grown stem cells will assist in reducing persistent inflammation in heart failure patients with LVAD.”
First Heart Failure Study to Involve Multiple Intravenous Injections of itMSCs
This is the first trial for which the FDA has approved multiple intravenous injections of mesenchymal stem cells; if safe and effective, this could potentially lead to a therapeutic strategy that would improve clinical function and would do so over the long-term. Importantly, virtually all previous attempts to use stem cells to treat cardiac disease delivered cells directly to the heart, which thereby eliminated one important mechanism by which intravenously administered MSCs might improve cardiac function—through a systemic anti-inflammatory effect. Previous studies also required catheter-based, invasive delivery strategies, which would be totally impractical if, as the MedStar Heart & Vascular Institute investigators suspect, repeated stem cell injections are required for adequate and sustained treatment effect.
“We have developed compelling evidence—using mouse models of heart attack and of heart failure—that one of the major mechanisms leading to progressive myocardial dysfunction in heart failure patients is the presence of persistent and inappropriate inflammation,” says Stephen Epstein, M.D., director of Translational and Vascular Biology Research at MedStar Heart & Vascular Institute. “We demonstrated that itMSCs have marked anti-inflammatory effects when injected intravenously to the mice, and that these anti-inflammatory effects led to markedly improved heart function.”
Dr. Ron Waksman, director of Cardiovascular Research and Advanced Education at MedStar Heart & Vascular Institute, added that “If we are successful in showing intravenously delivered itMSCs improve outcomes in LVAD patients, the results would likely extend to the general population of heart failure patients, and, in the process, fundamentally transform current paradigms for treating heart failure.”
Unlike MSCs from other sources that are grown under normal oxygen, or normoxic, conditions, CardioCell’s bone-marrow-derived, allogeneic itMSCs are grown under low-oxygen, or hypoxic, conditions. Compared to MSCs manufactured under normal oxygen conditions, our itMSCs secrete higher levels of growth factors and other important proteins associated with neoangiogenesis, healing, and powerful anti-inflammatory effects. The latter has been demonstrated in the pre-clinical and clinical studies cited in Circulation Research.
About the Severe Heart Failure Trial
Led by principal investigator Selma Mohammed, M.D., Ph.D., director of Research, Advanced Heart Failure Program, MedStar Heart & Vascular Institute, this Phase IIa, double blind, placebo-controlled, randomized study divides in half 30 subjects with advanced heart failure who are supported by LVADs. Enrolled subjects will be randomized at 1:1 into an experimental group (n=15) or a placebo group (n=15), respectively. Subjects in the experimental group will receive 1.5 million cells per kg, and subjects in the placebo group will receive 1.5 mL/kg of Ringer’s lactate solution at baseline, one month and two months.
“Innovative therapies to improve heart function and outcomes of patients with advanced heart failure are sorely needed,” says Mohammed.
Complete examinations will assess disability and functional status at baseline and at the visits scheduled at one, two, and three months after the initial administration. Also, at baseline and prior to each itMSC administration and at trial endpoint, trial administrators will analyze blood for levels of inflammatory cytokines, and at specified timepoints will perform 2D, 3D and Doppler transthoracic echocardiography with speckle-tracking and gated blood pool SPECT ventriculography for assessment of right and left ventricular systolic function and volumes.
All echocardiograms will be assessed in a blinded core lab. All SPECT ventriculograms will be assessed by a blinded observer. Subjects will continue all of their regular medications unless contraindicated. Endpoints assessed will be modulation of inflammatory cytokines, functional performance of the patient, and functional performance of the heart.
In addition to Drs. Waksman, Mohammed and Epstein, the following individuals made critically important contributions to the successful initiation and completion of the research leading to this clinical trial: Dr. Dror Luger, research scientist at MedStar Heart & Vascular Institute and Dr. Michael J. Lipinski, cardiologist at the Cardiovascular Associates of Charlottesville.
Founded in San Diego, California, in 2013, CardioCell is a global biotechnology company that explores therapeutic applications of unique patented ischemia-tolerant mesenchymal stem cells (itMSCs) manufactured under cGMP conditions. CardioCell has exclusive worldwide rights for the manufacturing, exploration and commercialization of itMSCs for therapeutic cardiovascular indications. For more information, visit www.stemcardiocell.com.