Clinical trial NCT04612413: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Sepsis
Community-acquired Pneumonia
Urinary Tract Infections
Cholecystitis, Acute
Cholangitis Acute
Intraabdominal Infections
Lead sponsor: Enlivex Therapeutics Ltd.
Sponsor class: INDUSTRY
First posted: 2020-11-03
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Up to Protocol Version 10.0, eligible patients were randomized to one of the 4 treatment groups in a 1:1:1:1 ratio between the 4 Cohorts:

1. Placebo
2. Single Intravenous (IV) dose of Allocetra-OTS, 5x10\^9 cells
3. Single IV dose of Allocetra-OTS, 10x10\^9 cells
4. Single or two IV doses of Allocetra-OTS, 10x10\^9 cells in each dose

Starting from Protocol Version 10.0, patient will be randomized to either Cohort 1 (Placebo) or Cohort 4 (Single or two IV doses of Allocetra-OTS, 10x10\^9 cells in each dose).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy: Change from baseline in SOFA score
timeFrame: 28 days
measure: Safety: Number and severity of AEs and SAEs
timeFrame: 28 days
Secondary outcomes:
measure: Ventilator-free days
timeFrame: 28 days
measure: Vasopressor-free days
timeFrame: 28 days
measure: Days without renal replacement therapy (dialysis).
timeFrame: 28 days
measure: Time in ICU and time in hospital
timeFrame: 28 days
measure: Number of days with creatinine ≤ Baseline levels +20%
timeFrame: 28 days
measure: All-cause mortality
timeFrame: 28 days
measure: Changes from baseline in CRP levels
timeFrame: 28 days
measure: Number and severity of AEs and Serious Adverse Events (SAEs)
timeFrame: 12 months
measure: Detection of autoimmune and human leukocyte antigen (HLA) antibodies
timeFrame: 12 months
Other outcomes:
Locations:
city: Brussel
country: Belgium
facility: Clinique Saint-Pierre
city: Brussel
country: Belgium
facility: Saint-Luc Hospital University
city: Charleroi
country: Belgium
facility: CHU de Charleroi
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
city: Angers
country: France
facility: CHU d'Angers
city: La Roche-sur-Yon
country: France
facility: Vendee Departmental Hospital Center
city: Limoges
country: France
facility: University Hospital of Limoges
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Bretonneau Hospital
city: Paris
country: France
facility: Centre Hospitalier Victor Dupouy
city: Reims
country: France
facility: Reims University Hospital Robert Debre
city: Rennes
country: France
facility: CHU de Rennes
city: Strasbourg
country: France
facility: Strasbourg University Hospital
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center
city: Petah tikva
country: Israel
facility: Beilinson Medical Center
city: Tverya
country: Israel
facility: Poriya Medical Center
city: Zefat
country: Israel
facility: Ziv Medical Center
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Hospital
city: Nijmegen
country: Netherlands
facility: Radboud UMC
city: Barcelona
country: Spain
facility: Clinic Barcelona University Hospital
city: Barcelona
country: Spain
facility: University Hospital Sagrat Cor
city: Barcelona
country: Spain
facility: Vall d'Hebron
city: Getafe
country: Spain
facility: Getafe University Hospital
city: Girona
country: Spain
facility: Dr. Josep Trueta University Hospital
city: Lleida
country: Spain
facility: University Hospital Arnau de Vilanova of Lleida
city: Madrid
country: Spain
facility: General University Hospital Gregorio Maranon
city: Tarragona
country: Spain
facility: University Hospital Joan XXIII of Tarragona
Study officials:
affiliation: Rabin medical center, Belinson Campus, Petah Tiqwa Isarel
name: Pierre Singer, MD
role: PRINCIPAL_INVESTIGATOR
References: