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

Phase 2

Active, not recruiting

• Conditions: Community-acquired Pneumonia; Sepsis; Cholecystitis, Acute; Urinary Tract Infections; Cholangitis Acute; Intraabdominal Infections
• Interventions: Other: Placebo; Drug: Allocetra-OTS

• Registration Number: NCT04612413
• Lead Sponsor: Enlivex Therapeutics Ltd.

Brief Summary

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

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 Timeline

• Study First Submitted: 2020-10-26
• Study First Submitted QC: 2020-11-01
• Study First Posted: 2020-11-03
• Study Start: 2020-11-30
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-12
• Last Update Posted: 2024-03-13
• Primary Completion: 2024-12-31
• Study Completion: 2025-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 160

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1	Placebo	Single IV dose of placebo solution
Cohort 4	Allocetra-OTS	Single or two doses of 10x10\^9 Allocetra-OTS cells in suspension
Cohort 2	Allocetra-OTS	Single IV dose of 5x10\^9 Allocetra-OTS cells in suspension
Cohort 3	Allocetra-OTS	Single IV dose of 10x10\^9 Allocetra-OTS cells in suspension

Primary Outcome Measures

Name	Time	Method
Safety: Number and severity of AEs and SAEs	28 days	Number and severity of AEs and SAEs throughout 28 days follow up period
Efficacy: Change from baseline in SOFA score	28 days	Change from baseline in SOFA score throughout 28 days

Secondary Outcome Measures

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

Trial Locations

Locations (31)

Radboud UMC; 🇳🇱 Nijmegen, Netherlands

CHU de Charleroi; 🇧🇪 Charleroi, Belgium

Ziekenhuis Oost-Limburg; 🇧🇪 Genk, Belgium

CHU de Montpellier; 🇫🇷 Montpellier, France

Beilinson Medical Center; 🇮🇱 Petah tikva, Israel

Ziv Medical Center; 🇮🇱 Zefat, Israel

CHU d'Angers; 🇫🇷 Angers, France

Saint-Luc Hospital University; 🇧🇪 Brussel, Belgium

Clinique Saint-Pierre; 🇧🇪 Brussel, Belgium

University Hospital of Limoges; 🇫🇷 Limoges, France

Clinic Barcelona University Hospital; 🇪🇸 Barcelona, Spain

Vendee Departmental Hospital Center; 🇫🇷 La Roche-sur-Yon, France

CHU de Nantes; 🇫🇷 Nantes, France

Bretonneau Hospital; 🇫🇷 Paris, France

Centre Hospitalier Victor Dupouy; 🇫🇷 Paris, France

Reims University Hospital Robert Debre; 🇫🇷 Reims, France

Soroka Medical Center; 🇮🇱 Be'er Sheva, Israel

Strasbourg University Hospital; 🇫🇷 Strasbourg, France

Bnai Zion Medical Center; 🇮🇱 Haifa, Israel

CHU de Rennes; 🇫🇷 Rennes, France

Hillel Yaffe Medical Center; 🇮🇱 Hadera, Israel

Hadassah Ein Kerem Medical Center; 🇮🇱 Jerusalem, Israel

Poriya Medical Center; 🇮🇱 Tverya, Israel

Canisius Wilhelmina Hospital; 🇳🇱 Nijmegen, Netherlands

Vall d'Hebron; 🇪🇸 Barcelona, Spain

University Hospital Sagrat Cor; 🇪🇸 Barcelona, Spain

Getafe University Hospital; 🇪🇸 Getafe, Spain

Dr. Josep Trueta University Hospital; 🇪🇸 Girona, Spain

University Hospital Arnau de Vilanova of Lleida; 🇪🇸 Lleida, Spain

University Hospital Joan XXIII of Tarragona; 🇪🇸 Tarragona, Spain

General University Hospital Gregorio Maranon; 🇪🇸 Madrid, Spain