Cholangitis Acute, Cholecystitis, Acute, Community-acquired Pneumonia, Intraabdominal Infections, Sepsis, Urinary Tract Infections
Conditions
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.
Interventions
DRUGAllocetra-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.
OTHERPlacebo
Solution containing all excipients except for the Allocetra-OTS cells
Sponsors
Enlivex Therapeutics Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Change from baseline in SOFA score | 28 days | Change from baseline in SOFA score throughout 28 days |
| Safety: Number and severity of AEs and SAEs | 28 days | Number and severity of AEs and SAEs throughout 28 days follow up period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days without renal replacement therapy (dialysis). | 28 days | Days without renal replacement therapy (dialysis). |
| Time in ICU and time in hospital | 28 days | Time in ICU and time in hospital |
| 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 |
| Changes from baseline in CRP levels | 28 days | Changes from baseline in CRP levels |
| 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 |
| Detection of autoimmune and human leukocyte antigen (HLA) antibodies | 12 months | Detection of autoimmune and human leukocyte antigen (HLA) antibodies |
| All-cause mortality | 28 days | All-cause mortality at Day 28 following first dose |
| Vasopressor-free days | 28 days | Vasopressor-free days over 28 days. |
Countries
Belgium, France, Israel, Netherlands, Spain
Outcome results
None listed