Phase 2 Sepsis Cell Therapy Trial Cleared to Expand into France and Belgium

Enlivex has received clearance from the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) and the Belgian Federal Agency for Medicines and Health Products (FAMHP) to expand recruitment for its phase 2 clinical trial (NCT04612413) of Allocetra into France and Belgium.¹

Allocetra is an investigational allogeneic macrophage-reprogramming cell therapy intended to treat various indications. The study had previously been approved for the treatment of patients with pneumonia-associated sepsis in Israel, Greece, and Spain. In addition to the expansion into France and Belgium, Enlivex has also now received clearance to include patients with sepsis related to biliary, urinary tract, or abdominal infections. Allocetra was previously evaluated in a phase 1b trial for patients with sepsis and demonstrated improvements in terms of Sequential Organ Failure Assessment (SOFA) scores, hospitalization duration, and mortality in comparison to matched historical control patients who received standard-of-care treatment.

In addition to sepsis, Allocetra is also being evaluated for the treatment of patients with peritoneal metastasis (NCT05431907), and patients with COVID-19 (NCT04659304, NCT04922957). In August 2022, it was also announced that the Israeli Ministry of Health (MOH) approved the initiation of a phase 1/2 clinical trial (NCT05581719) to investigate Allocetra, both alone and in combination with a PD-1 checkpoint inhibitor, for the treatment of solid tumors.²

"Expanding the study to France and Belgium with frozen formulation Allocetra is an important step in the execution of our ongoing phase 2 sepsis trial,” Oren Hershkovitz, PhD, chief executive officer, Enlivex, said in a statement regarding the news.¹ “We also believe that this is a notable regulatory achievement that provides additional validation for our amended study design and Allocetra frozen formulation."

The multicenter, placebo-controlled, randomized, dose-finding study will seek to recruit 80 to 160 patients aged 18 years to 90 years who meet sepsis 3 criteria. Participants are required to have adequate source control. Patients who are on chronic dialysis, those with acute pancreatitis, patients with invasive ventilation and PaO2/FiO2 less than 100 mmHg, patients with a SOFA score of 10 or higher, nosocomial infection, a known malignancy, chronic respiratory disease, active upper GI tract ulceration or hepatic dysfunction, and those with organ allograft or previous history of stem cell transplantation will be excluded from the study. Additional exclusion criteria include a known immunocompromised state; use of medications known to be immunosuppressive; known New York Heart Association class IV heart failure or unstable angina, ventricular arrhythmias, acute coronary disease, or myocardial infarction; and known active symptomatic SARS-CoV-2, chronic viral infections, or other chronic infections.

Patients will be divided across 4 cohorts, with patients in cohort 1 receiving a placebo solution, patients in cohort 2 receiving a single dose of 5x10⁹ Allocetra cells in suspension, patients in cohort 3 receiving a single dose of 10x10⁹ Allocetra cells in suspension, and patients in cohort 4 receiving either 1 or 2 doses of 10x10⁹ Allocetra cells in suspension. All patients in the study will also receive standard-of-care therapy. The study’s primary end points are the change from baseline in SOFA score and the number and severity of adverse events (AEs) and serious AEs throughout 28 days. Secondary end points include all-cause mortality, ventilator-free days, vasopressor-free days, days without dialysis, time in ICU and time in hospital, the number of days with creatinine less than or equal to baseline levels +20%, changes from baseline in C-reactive protein (CRP) levels, the detection of autoimmune and HLA antibodies, and the number and severity of AEs and serious AEs throughout 12 months of follow-up. The study has an estimated completion date of September 1, 2024.

REFERENCES

1. Enlivex receives authorizations from French and Belgian regulatory agencies to expand its phase II sepsis clinical trial into France and Belgium. News release. Enlivex Therapeutics Ltd. January 4, 2023. https://finance.yahoo.com/news/enlivex-receives-authorizations-french-belgian-130000145.html 

2. Enlivex receives Israeli Ministry of Health approval for the initiation of a phase I/II trial evaluating Allocetra alone and in combination with a PD1 checkpoint inhibitor in patients with advanced solid tumors. News release. Enlivex Therapeutics Ltd. August 17, 2022. https://www.globenewswire.com/news-release/2022/08/17/2499939/0/en/Enlivex-Receives-Israeli-Ministry-of-Health-Approval-for-the-Initiation-of-a-Phase-I-II-Trial-Evaluating-Allocetra-Alone-and-in-Combination-with-a-PD1-Checkpoint-Inhibitor-in-Patie.html