Phase II year
2017
(last award dollars: 2019)
Phase II Amount
$1,941,300
Exploratory Clinical Study to Evaluate the Potential Bioactivity of CLBS14 in Patients with Coronary Microvascular Dysfunction Project Summary/Abstract CLBS14 is an autologous cell therapy consisting of G-CSF mobilized autologous CD34+ cells obtained from peripheral blood. The primary mode of action is improvement in perfusion by neo-angiogenesis and/or microvascular function under conditions of inadequate perfusion. The therapeutic focus of the proposed clinical study is coronary microvascular dysfunction (CMD), for which therapeutic strategies are limited. Approximately 20 subjects with CMD will be enrolled in the single arm study. The primary objective is to evaluate the potential bioactivity of intracoronary delivery of autologous CD34+ cells (CLBS14) in subjects with CMD and no obstructive coronary artery disease, as determined by invasive testing of coronary microvascular function as determined by assessment of coronary flow reserve (CFR). Additional data will be collected on endothelial-dependent microvascular function as determined by measurement of coronary blood flow in reaction to acetylcholine; endothelial-independent microvascular function as determined by measurement of coronary blood flow in reaction to adenosine; peripheral arterial tonometry; quality of life as measured with an angina diary, Seattle Angina Questionnaire (SAQ), and a health-related quality of life questionnaire; exercise tolerance as assessed by treadmill testing and by recording of daily activities with a Fitbit®. The study is being designed and implemented by well-regarded investigators in CD34+ cell therapy and ischemic cardiac disease. Dr. Douglas Losordo from Caladrius Biosciences is the sponsor and study director and the investigators are Dr. Timothy Henry and Noel Bairey Merz of Cedars-Sinai Medical Center and Dr. Amir Lerman of the Mayo Clinic. Cedars-Sinai and Mayo Clinic are co investigators on the grant. Product manufacturing is provided by PCT, a Caladrius Company and a recognized leader in contract cell therapy manufacturing. For preparation of CLBS14, each patient is treated with G-CSF for up to 5 days to mobilize CD34+ cells from the bone marrow and into peripheral blood. Each patient undergoes apheresis to provide the starting material for manufacturing CLBS14. The apheresis material is processed to separate and enrich CD34+ cells, which are then formulated for administration back to the patient via intra-coronary infusion. Following infusion of CLBS14, patients are monitored for safety and efficacy endpoints for up to one year. It is expected that the trial will take approximately 2 years to complete. Results from the research will be presented in one or more public forums and published in a peer-reviewed journal. With the novel angiogenic mechanism of action of CLBS14 and specifically targeting coronary microvascular dysfunction to improve coronary microvascular flow responsible for the major adverse cardiac events and poor quality of life in this population, this project will be a strong contributor to NIHs mission to develop new and effective therapies for underserved diseases. Caladrius Biosciences - Proprietary and Confidential
Public Health Relevance Statement: Exploratory Clinical Study to Evaluate the Potential Bioactivity of CLBS14 in Patients with Coronary Microvascular Dysfunction Project Narrative Coronary microvascular dysfunction (CMD), which predominantly effects women, causes ischemic chest pain and increases the risk of major adverse coronary events however at present, there is no specific therapy available to treat CMD. CLBS14 is an autologous cell therapy consisting of G-CSF mobilized autologous CD34+ cells obtained from peripheral blood which has been shown promote angiogenesis under conditions of inadequate perfusion, such as CMD. This study will test the hypothesis that CLBS14 improves microvascular function in CMD patients and may therefore improves symptoms and outcomes in the setting of this currently unmet medical need. Caladrius Biosciences - Proprietary and Confidential
Project Terms: Acetylcholine; Acute myocardial infarction; Address; Adenosine; angiogenesis; arm; arterial tonometry; associated symptom; Autologous; Back; Biological Sciences; Blood Component Removal; Blood flow; bone cell; Bone Marrow; Cardiac; Cardiovascular Diseases; Cardiovascular system; CD34 gene; Cell Therapy; Cells; Characteristics; Chest; Chest Pain; Clinic; Clinical Research; Clinical Trials; commercialization; Contracts; Coronary; Coronary Arteriosclerosis; CSF3 gene; Data; Death, Sudden, Cardiac; design; Development; diaries; Disease; double-blind placebo controlled trial; effective therapy; EFRAC; Enrollment; Event; Exercise Tolerance; experience; fitbit; functional outcomes; Grant; health related quality of life; Heart Diseases; Heart failure; Hospitalization; improved; improved outcome; Infusion procedures; innovation; Ischemia; Journals; Laboratories; Manufactured Materials; Measurement; Measures; Medical; Medical center; Microcirculation; Microvascular Dysfunction; Mission; Myocardial Ischemia; neovascularization; novel; novel therapeutics; outcome forecast; Patient Monitoring; Patients; Peer Review; Perfusion; Peripheral; peripheral blood; Phase; Population; pre-clinical; Preparation; Process; Publishing; Quality of life; Questionnaires; Randomized; Reaction; Regenerative Medicine; repaired; Reporting; Research; Research Personnel; Risk; Safety; Secondary to; symptomatic improvement; Symptoms; Syndrome; Testing; Therapeutic; tissue repair; Tissues; Treadmill Tests; United States National Institutes of Health; Woman
