Cell Directed Immunomodulation Therapy as a Bridge to Left Ventricular Device Implantation in Chronic Heart Failure Patients

Abstract The Problem. Cardiovascular disease is the leading cause of mortality in the US, accounting for 45% of all deaths. Chronic Heart Failure (CHF) is now understood to be a multi-system disease process involving not only the cardiovascular system but also the renal, neuroendocrine and immune systems. No effective therapy is currently available to treat the most severe subset of CHF patients that have progressed to acute decompensated HF. An innovative approach to reduce the cardio-depressant effects associated with the chronic inflammatory state of CHF may provide a breakthrough for this disorder. This proposal will evaluate the safety and probable benefit to improve cardiac or renal function with an immunomodulatory device to bridge patients to Left Ventricular Assist Device (LVAD) implantation deemed ineligible for this life sustaining procedure. If the trial is successful, a pathway to commercialization via a Humanitarian Device Exemption (HDE) would be available for rapid use in this patient population whose life expectancy is days to weeks. The Product. The Selective Cytopheretic Device (SCD) is an immuno-regulating, extracorporeal, membrane device targeted to modulate the cardio-depressant effects that are associated with CHF. SCD is a platform technology focused on immunomodulation of acute and chronic inflammation associated with acute and chronic organ dysfunction. SCD membranes selectively sequester activated systemic leukocytes as they flow through the cartridge via an extracorporeal circuit. Pre-clinical results show SCD treatment results in a 25% improvement in ejection fraction in a canine CHF model. Innovation. SCD is an innovative approach to treat CHF. Rather than utilizing small molecules to improve myocardial contractility, SCD acts as an immunomodulatory device to dampen the cardio-depressant effects of the chronic pro-inflammatory state of CHF. This proposal will provide the first clinical support for the use of immunomodulatory treatment for chronically inflamed CHF patients. Phase Il Hypothesis. SCD treatment will demonstrate safety and probable benefit as a bridge to LVAD implantation in a previously ineligible CHF patient population. This Phase Il plan is based upon results demonstrating SCD treatment improved cardiac contractility in a canine model of CHF and an ongoing clinical trial demonstrating first in human, proof of concept of successful bridge to LVAD in an ineligible patient with severe CHF with improvement of cardiac performance. Aim. To expand a current single center IDE clinical trial to a multicenter trial to enroll 20 patients in 4 centers for evaluation of safety and probable benefit of SCD treatment for a Humanitarian Device Exemption (HDE) application for a severely ill patient population to bridge to a life sustaining LVAD implantation. Commercial Opportunity. This proposed single clinical trial which demonstrates safety and probable benefit will support a HDE submission for FDA approval and commercialization.