Israeli Ministry of Health Authorizes Trial Evaluating Allocetra in Sepsis Patients

Enlivex Therapeutics reported the Israeli Ministry of Health authorized the initiation of a proposed Company-sponsored Phase IIb clinical trial evaluating Allocetra™, in sepsis patients.

The planned Company-sponsored Phase IIb clinical trial is a multi-center, randomized, placebo-controlled study, which is expected to recruit up to 160 sepsis patients in four cohorts, and is designed to assess Allocetra™ treatment in combination with standard of care treatment. The trial plans to evaluate safety, tolerability, and efficacy parameters of different doses of Allocetra™, and has two co-primary endpoints: (i) change from baseline in Sequential Organ Failure Assessment (SOFA) score over a period of 28 days, and (ii) number and severity of adverse events and serious adverse events. Secondary endpoints include (i) number of ventilator-free days, (ii) number of vasopressor-free days, (iii) number of days without renal replacement therapy (dialysis), and (iv) length of stay in Intensive Care Unit or Intermediate Care Unit and in hospital.

On March 18, 2020, the Company announced the final safety and efficacy data from the Company’s completed Phase Ib trial in patients with sepsis. The final analysis compared the clinical data of 10 patients admitted to the intensive care unit with sepsis who were administered Allocetra™ upon their admission, with 37 patients who were matched controls (matched by age, gender, SOFA score, and infection source) who received only the standard of care treatment at the same hospital during 2014-2019. The clinical trial was conducted at Hadassah Medical Center, which is one of the largest and most prestigious hospitals in Israel. The Acute Physiology and Chronic Health Evaluation (APACHEII) score of the Allocetra™-treated group was 12.3, and the corresponding probability of mortality of at least one patient in that group was predicted at 85% based on the hospital’s ICU staff’s clinical assessment of each patient’s overall condition at admission. However, none (0%) of the Allocetra™-treated patients died during the 28-day study period, as compared to 27% 28-day mortality in the matched controls group. Each of the 10 Allocetra™-treated patients had between 2 to 5 dysfunctional organ systems upon admission to the ICU. All (100%) of the Allocetra™-treated patients had rapid and complete recovery from their septic conditions and of any organ dysfunction that was present upon admission to the ICU. Despite the similarity of organ-failure state (SOFA) at entry between the Allocetra™-treated patients and the matched control group (average of 3.4 versus 3.47), not a single patient treated with Allocetra™ had any increase in organ-failure state post administration of Allocetra™, while the majority of the patients in the matched control group had an increase in organ-failure state. The average worsening in organ-failure state of patients in the matched control group was approximately 100% compared with their ICU hospitalization state vs zero (0%) percent worsening in organ-failure state of Allocetra™-treated patients post administration of Allocetra™ (p< <0.0001). The ICU length-of-stay for all Allocetra™-treated patients was significantly shorter than that of those patients who received only the standard of care, with an average of 4 days compared to 11.11 days in the matched controls group, a 64% reduction (p<0.0001). The slowest ICU discharge of a patient treated with Allocetra™ was after 8 days, while approximately 50% of the matched control group were still at the ICU after 28 days. Allocetra™ was shown to be safe and tolerable, with no serious unexpected severe adverse reactions and no serious adverse events.

Allocetra™ is also being developed for treatment of COVID-19 patients in severe and critical condition. The Company reported on October 21, 2020 that the first two patients have been dosed in an investigator-initiated Phase II clinical trial evaluating Allocetra™ in severe and critical COVID-19 patients. The COVID-19 study was designed as a multi-center, investigator-initiated, Phase II clinical trial. The trial is expected to recruit up to twenty- four COVID-19 patients in severe or critical condition and is designed to assess Allocetra™ in combination with standard of care treatment. The trial plans to evaluate safety, tolerability, cytokine profile and efficacy parameters. Each patient in the clinical trial will be observed for 28 days following administration of Allocetra™. The Phase II COVID-19 study follows recently reported positive top-line results from a Phase Ib investigator-initiated clinical trial of Allocetra™ in COVID-19 patients in severe and critical condition. The Phase Ib COVID-19 study took place in Hadassah Hospital, one of the largest hospitals in Israel, and included five COVID-19 patients, three in severe condition and two in critical condition. All five patients completely recovered from their respective severe/critical condition and were released from the hospital after an average of 5 days (severe) and 9 days (critical), following administration of Allocetra™, at which time they were all COVID-19 PCR negative. There were no reported severe adverse events relating to the administration of Allocetra™ in the patients, and the therapy was well-tolerated.