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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Sepsis, Community-acquired Pneumonia, Urinary Tract Infections, Cholecystitis, Acute, Cholangitis Acute, Intraabdominal Infections

Intervention / Treatment
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* Drug: Allocetra-OTS
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 years and ≤90 years of age. Meets Sepsis 3 criteria with a SOFA score ≥5 above pre-admission status 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 Adequate source control Exclusion Criteria: 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. On chronic dialysis. Patients with acute pancreatitis Moribund patients Weight <50 kg or >120 kg or BMI >40 kg/m^2. SOFA score ≥14 at screening. Patients with nosocomial infection. A known malignancy. Patients with end-stage disease (unrelated to sepsis) Known active symptomatic SARS-CoV-2 or chronic viral infections, such as HBV or HCV, HIV or other chronic infections. Chronic respiratory disease. Known active upper GI tract ulceration or hepatic dysfunction. Known NYHA class IV heart failure or unstable angina, ventricular arrhythmias, acute coronary disease or myocardial infarction. Known immunocompromised state or medications known to be immunosuppressive. Organ allograft or previous history of stem cell transplantation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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: Placebo Single Intravenous (IV) dose of Allocetra-OTS, 5x10^9 cells Single IV dose of Allocetra-OTS, 10x10^9 cells 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).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Cohort 1<br>Single IV dose of placebo solution | Other: Placebo<br>* Solution containing all excipients except for the Allocetra-OTS cells<br>|
| Experimental: Cohort 2<br>Single IV dose of 5x10^9 Allocetra-OTS cells in suspension | Drug: Allocetra-OTS<br>* 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.<br>|
| Experimental: Cohort 3<br>Single IV dose of 10x10^9 Allocetra-OTS cells in suspension | Drug: Allocetra-OTS<br>* 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.<br>|
| Experimental: Cohort 4<br>Single or two doses of 10x10^9 Allocetra-OTS cells in suspension | Drug: Allocetra-OTS<br>* 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.<br>|

What is the study measuring?
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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 |