A Phase 2 Study Evaluating Efficacy, Safety and Tolerability of Different Doses and Regimens of Allocetra-OTS for the Treatment of Organ Failure in Adult Sepsis Patients

A Phase 2, Multi-Center, Randomized, Placebo-Controlled, Dose-Finding Study Evaluating Efficacy, Safety and Tolerability of Different Doses and Regimens of Allocetra-OTS for the Treatment of Organ Failure in Adult Sepsis Patients

A Phase 2, Multi-Center, Randomized, Placebo-Controlled, Dose-Finding Study Evaluating Efficacy, Safety and Tolerability of Different Doses and Regimens of Allocetra-OTS for the Treatment of Organ Failure in Adult Sepsis Patients

Study Overview

• Status: Completed
• Conditions: Sepsis; Intraabdominal Infections; Cholecystitis, Acute; Urinary Tract Infections; Community-acquired Pneumonia; Cholangitis Acute
• Intervention / Treatment: Other: Placebo; Drug: Allocetra-OTS

Detailed Description

Allocetra-OTS is an immunomodulatory cell-based therapy consisting of allogeneic peripheral blood mononuclear cells that have been modified to be engulfed by macrophages and reprogram them into their homeostatic state.

This is a multi-center, randomized, placebo-controlled, dose-finding study comparing the efficacy, safety and tolerability of different dosing regimens of Allocetra-OTS, in patients with sepsis. The study aims to compare the safety and efficacy of different doses and regimens of Allocetra-OTS, as well as the clinical manifestations following Allocetra-OTS treatment, to that of Placebo in the treatment of organ failure in adult sepsis patients.

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium
    • Clinique Saint-Pierre
  • Brussel, Belgium
    • Saint-Luc Hospital University
  • Charleroi, Belgium
    • CHU de Charleroi
  • Genk, Belgium
    • Ziekenhuis Oost-Limburg
• France
  • Angers, France
    • CHU d'Angers
  • La Roche-sur-Yon, France
    • Vendée Departmental Hospital center
  • Limoges, France
    • University Hospital of Limoges
  • Montpellier, France
    • CHU de Montpellier
  • Nantes, France
    • CHU de Nantes
  • Paris, France
    • Bretonneau Hospital
  • Paris, France
    • Centre Hospitalier Victor Dupouy
  • Reims, France
    • Reims University Hospital Robert Debre
  • Rennes, France
    • CHU de Rennes
  • Strasbourg, France
    • Strasbourg University Hospital
• Israel
  • Be'er Sheva, Israel
    • Soroka Medical Center
  • Hadera, Israel
    • Hillel Yaffe Medical Center
  • Haifa, Israel
    • Bnai Zion Medical Center
  • Jerusalem, Israel
    • Hadassah Ein Kerem Medical Center
  • Petah tikva, Israel
    • Beilinson medical center
  • Tverya, Israel
    • Poriya Medical Center
  • Zefat, Israel
    • Ziv Medical Center
• Netherlands
  • Nijmegen, Netherlands
    • Radboud UMC
  • Nijmegen, Netherlands
    • Canisius Wilhelmina Hospital
• Spain
  • Barcelona, Spain
    • Vall d'Hebron
  • Barcelona, Spain
    • Clinic Barcelona University Hospital
  • Barcelona, Spain
    • University Hospital Sagrat Cor
  • Getafe, Spain
    • Getafe University Hospital
  • Girona, Spain
    • Dr. Josep Trueta University Hospital
  • Lleida, Spain
    • University Hospital Arnau de Vilanova of Lleida
  • Madrid, Spain
    • General University Hospital Gregorio Maranon
  • Tarragona, Spain
    • University Hospital Joan XXIII of Tarragona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female ≥18 years and ≤90 years of age.
2. Meets Sepsis 3 criteria with a SOFA score ≥5 above pre-admission status

3. Sepsis due to infection in at least one of the below organs:

   3.1. Community-Acquired Pneumonia (CAP). 3.2. Urinary tract infection 3.3. Acute cholecystitis diagnosed by Tokyo criteria 3.4. Acute cholangitis diagnosed by Tokyo criteria 3.5. Other intra-abdominal infections (IAI) 3.6. Skin or soft tissue infection

4. Adequate source control

Exclusion Criteria:

1. Sepsis due to infection other than lung infection, UTI, IAI, skin/soft tissue infection or sepsis patients where site of infection is unclear or unknown.
2. On chronic dialysis.
3. Patients with acute pancreatitis
4. Moribund patients
5. Weight <50 kg or >120 kg or BMI >40 kg/m^2.
6. SOFA score ≥14 at screening.
7. Patients with nosocomial infection.
8. A known malignancy.
9. Patients with end-stage disease (unrelated to sepsis)
10. Known active symptomatic SARS-CoV-2 or chronic viral infections, such as HBV or HCV, HIV or other chronic infections.
11. Chronic respiratory disease.
12. Known active upper GI tract ulceration or hepatic dysfunction.
13. Known NYHA class IV heart failure or unstable angina, ventricular arrhythmias, acute coronary disease or myocardial infarction.
14. Known immunocompromised state or medications known to be immunosuppressive.
15. Organ allograft or previous history of stem cell transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Cohort 1; Single IV dose of placebo solution	Other: Placebo; Solution containing all excipients except for the Allocetra-OTS cells
Experimental: Cohort 2; Single IV dose of 5x10^9 Allocetra-OTS cells in suspension	Drug: Allocetra-OTS; Allocetra-OTS is a cell-based therapy consisting of non-HLA-matched allogeneic peripheral blood mononuclear cells, derived from a healthy human donor following a leukapheresis procedure, induced to an apoptotic stable state and suspended in a solution containing DMSO.
Experimental: Cohort 3; Single IV dose of 10x10^9 Allocetra-OTS cells in suspension	Drug: Allocetra-OTS; Allocetra-OTS is a cell-based therapy consisting of non-HLA-matched allogeneic peripheral blood mononuclear cells, derived from a healthy human donor following a leukapheresis procedure, induced to an apoptotic stable state and suspended in a solution containing DMSO.
Experimental: Cohort 4; Single or two doses of 10x10^9 Allocetra-OTS cells in suspension	Drug: Allocetra-OTS; Allocetra-OTS is a cell-based therapy consisting of non-HLA-matched allogeneic peripheral blood mononuclear cells, derived from a healthy human donor following a leukapheresis procedure, induced to an apoptotic stable state and suspended in a solution containing DMSO.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Change from baseline in SOFA score	Change from baseline in SOFA score throughout 28 days	28 days
Safety: Number and severity of AEs and SAEs	Number and severity of AEs and SAEs throughout 28 days follow up period	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-free days	Ventilator-free days over 28 days	28 days
Vasopressor-free days	Vasopressor-free days over 28 days.	28 days
Days without renal replacement therapy (dialysis).	Days without renal replacement therapy (dialysis).	28 days
Time in ICU and time in hospital	Time in ICU and time in hospital	28 days
Number of days with creatinine ≤ Baseline levels +20%	Number of days with creatinine ≤ Baseline levels +20%	28 days
All-cause mortality	All-cause mortality at Day 28 following first dose	28 days
Changes from baseline in CRP levels	Changes from baseline in CRP levels	28 days
Number and severity of AEs and Serious Adverse Events (SAEs)	Number and severity of AEs and Serious Adverse Events (SAEs) throughout 12 months follow up period	12 months
Detection of autoimmune and human leukocyte antigen (HLA) antibodies	Detection of autoimmune and human leukocyte antigen (HLA) antibodies	12 months

Collaborators and Investigators

• Sponsor: Enlivex Therapeutics Ltd.
• Collaborators: Cato Research; Accelsiors CRO & Consultancy Services
• Investigators: Principal Investigator: Pierre Singer, MD, Rabin medical center, Belinson Campus, Petah Tiqwa Isarel

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2020
• Primary Completion (Actual): January 12, 2024
• Study Completion (Actual): December 16, 2024

Study Registration Dates

• First Submitted: October 26, 2020
• First Submitted That Met QC Criteria: November 1, 2020
• First Posted (Actual): November 3, 2020

Study Record Updates

• Last Update Posted (Actual): August 19, 2025
• Last Update Submitted That Met QC Criteria: August 18, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Digestive System Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Biliary Tract Diseases; Bile Duct Diseases; Gallbladder Diseases; Sepsis; Infections; Communicable Diseases; Cholangitis; Urinary Tract Infections; Toxemia; Intraabdominal Infections; Cholecystitis; Cholecystitis, Acute
• Other Study ID Numbers: ENX-CL-02-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No