The Belgium-based biotechnology company, TiGenix, has launched a clinical trial entitled SEPCELL that uses fat-derived stem cells (called Cx611) to treat severe sepsis secondary to acquired pneumonia (also known as sCAP). SEPCELL is a randomized, double-blind, placebo-controlled, Phase 1b/2a study of sCAP patients who require mechanical ventilation and/or vasopressors.
SEPCELL will, hopefully, enroll 180 patients and will be conducted at approximately 50 centers throughout Europe. Subjects who participate in this trial will be randomly assigned to receive either an investigational product or placebo on days 1 and 3. All patients will be treated with standard care, which usually includes broad-spectrum antibiotics and anti-inflammatory drugs.
The primary endpoint of this clinical trial will examine the number, frequency, and type of adverse reactions during the 90-day period of the trial. The secondary endpoints of the SEPCELL trial include reduction in the duration of mechanical ventilation and/or vasopressors, overall survival, clinical cure of sCAP, and other infection-related endpoints. SEPCELL will also assess the safety and efficacy of the expanded allogeneic adipose stem cells (eASCs) that will be intravenously delivered to some of the patients in this study.
The SEPCELL trial will be managed by TFS International, a company based in Lund, Sweden. TFS has extensive experience in running sepsis trials and hospital-based trials.
Sepsis is a potentially life-threatening complication of infection that occurs when inflammatory molecules (cytokines and chemokines) released into the bloodstream to fight the infection trigger systemic inflammation. This body-wide inflammation has the ability to trigger a cascade of detrimental changes that damage multiple organ systems and cause them to fail. If sepsis progresses to “septic shock,” blood pressure drops dramatically, which may lead to death. Patients with “severe sepsis” require close monitoring and treatment in a hospital intensive care unit. Drug therapy is likely to include broad-spectrum antibiotics, corticosteroids, vasopressor drugs to increase blood pressure, as well as oxygen and large amounts of intravenous fluids. Supportive therapy may be needed to stabilize breathing and heart function and to replace kidney function. Patients with severe sepsis have a low survival rate so there is a critical need to improve the effectiveness of current therapy. Only a small number of new molecular entities are currently in development for severe sepsis.
Severe sepsis and septic shock significantly affect public health and these event also are leading causes of mortality in intensive care units.
Severe sepsis and septic shock have an incidence of about 3 cases per 1,000, but due to the aging of the population and an increase in drug resistant bacteria.
Cx611 is an intravenously-administered concoction that consists of allogeneic eASCs. These cells are largely mesenchymal stem cells that secrete an impressive array of molecules that suppress the type of immune responses that damage organs during events like septic shock. eASCs have a higher proliferation rate in culture and faster attachment than bone marrow-based mesenchymal stem cells in cell culture. ASCs are also less prone to senescence and differentiation. Their differentiation capacity decreases with expansion time without losing immunomodulatory properties. These eASCs also have superior inflammation targeting capacities than bone marrow-based mesenchymal stem cells, and are safe, since they do not express ligands for receptors on Natural Killer cells that, and therefore, are unlikely to elicit an immune rejection.
In May 2015, TiGenix completed a Phase 1 sepsis challenge that demonstrated that Cx611 is safe and well tolerated. That trial began in December 2014, and was a placebo-controlled dose-ranging study (3 doses of eASC’s) in which 32 healthy male volunteers were randomized to receive Cx611 or placebo in a ratio of 3:1. Primary endpoints were vital signs and symptoms, laboratory measures and functional assays of innate immunity. All 32 volunteer subjects were recruited and dosed by March 2015. By May, 2015, the phase I trial data essentially demonstrated the safety and tolerability of Cx611. On the strength of that phase I trial, TiGenix designed a Phase 1b/2a trial in severe sepsis secondary to sCAP in which they expecet to enroll 180 subjects across Europe.
SEPCELL was funded by a €5.4 million grant ($6.14 million) from the European Union.