Study Treatment
ADVERSE EVENTS
PLX-R18 is an allogeneic ex-vivo placental expanded adherent stromal cell product derived from full-term human placentae of healthy women undergoing an elective caesarean section (see supplementary information All patients were treated with PLX-R18 in addition to standard of care, including blood product transfusions and HGF, as deemed clinically necessary by the investigators. The first 3 patients were assigned to Cohort 1 (1 million cells/kg/administration), the next 6 patients to Cohort 2 (2 million cells/kg/administration) and the last 12 patients to Cohort 3 (4 million cells/kg/administration). Each patient received 2 administrations of PLX-R18, 7 days apart. Individual dose and number of injections was calculated for each patient based on cohort assignment, body weight, and PLX-R18 cell concentration. Maximal dose was not to exceed 400 million cells per administration session; maximal volume not to exceed 1.5 mL per injection site. The required total dose of PLX-R18 was injected in multiple intramuscular (IM) injections, preferably bilaterally, into the gluteus medius and thigh muscles. All patients were pre-treated with an antihistamine, and if desired a topical anesthetic at the planned injection sites. All patients were hospitalized for 24 h after each administration to closely monitor short term adverse events (AEs). To minimize risk, patients were treated sequentially, with a minimal pre-defined lapse (4 weeks from first dose) between cohorts, and with the oversight of an independent Data Safety Monitoring Board that assessed safety data in an ongoing manner and prior to dose escalation. The highest dose, 4 million cells/kg, is 10-fold lower than the dose proven to be safe in toxicology murine and non-human-primates (NHP) studies. NHP data further supported this dose as sufficient to demonstrate a response. The IM route of administration was selected following murine and NHP studies showing favorable persistence following IM administration [