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

Sepsis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04612413
• Other study ID #: ENX-CL-02-002
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 30, 2020
• Est. completion date: March 31, 2025

Study information

• Verified date: March 2024
• Source: Enlivex Therapeutics Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 160
• Est. completion date: March 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cholangitis
• Cholecystitis
• Cholecystitis, Acute
• Communicable Diseases
• Community-acquired Pneumonia
• Infections
• Intraabdominal Infections
• Sepsis
• Toxemia
• Urinary Tract Infections

Intervention

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.

Other:
• Placebo
Solution containing all excipients except for the Allocetra-OTS cells

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Enlivex Therapeutics Ltd.

Countries where clinical trial is conducted

Belgium,  France,  Israel,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy: Change from baseline in SOFA score	Change from baseline in SOFA score throughout 28 days	28 days
Primary	Safety: Number and severity of AEs and SAEs	Number and severity of AEs and SAEs throughout 28 days follow up period	28 days
Secondary	Ventilator-free days	Ventilator-free days over 28 days	28 days
Secondary	Vasopressor-free days	Vasopressor-free days over 28 days.	28 days
Secondary	Days without renal replacement therapy (dialysis).	Days without renal replacement therapy (dialysis).	28 days
Secondary	Time in ICU and time in hospital	Time in ICU and time in hospital	28 days
Secondary	Number of days with creatinine = Baseline levels +20%	Number of days with creatinine = Baseline levels +20%	28 days
Secondary	All-cause mortality	All-cause mortality at Day 28 following first dose	28 days
Secondary	Changes from baseline in CRP levels	Changes from baseline in CRP levels	28 days
Secondary	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
Secondary	Detection of autoimmune and human leukocyte antigen (HLA) antibodies	Detection of autoimmune and human leukocyte antigen (HLA) antibodies	12 months