Prevention of Sepsis-related Organ Dysfunction With Allocetra-OTS

Study Overview
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Brief Summary
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The trial evaluates the safety and efficacy of one and two doses of the study drug, Allocetra-OTS, in patients who have been diagnosed with sepsis.

Detailed Description
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The study drug, Allocetra-OTS is a cell-based therapeutic composed of donor apoptotic cells. The product contains allogeneic mononuclear enriched cells in the form of a liquid suspension with at least 40% early apoptotic cells. The study drug, Allocetra-OTS, is based on the known activity of apoptotic cells to contribute to maintenance of peripheral immune homeostasis. As altered immune response is associated with organ dysfunction in sepsis, the possibility is being tested that the study drug can improve the condition of sepsis.

Official Title
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Prevention of Sepsis-related Organ Dysfunction With Allocetra-OTS

Conditions
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Organ Dysfunction Syndrome Sepsis

Intervention / Treatment
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* Biological: Allocetra-OTS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Suspected, presumed or documented infection from any source. Initiation of antibiotics. Meets Sepsis 3 criteria: The presence of organ dysfunction as identified by a total SOFA score ≥ 2 points above baseline. Adult male or female, age between 18 and 85. GCS of >13 with verbal score of 5. Signed written informed consent by the patient. Exclusion Criteria: Participation in an interventional investigational trial within 30 days prior to diagnosis of sepsis. Significant trauma requiring hospitalization within 30 days prior to diagnosis of sepsis. Surgical intervention or hospitalization within 45 days prior to diagnosis of sepsis. Pregnancy or breast-feeding female. Progressive or poorly-controlled malignancies or < 6 month after active treatment for cancer (chemotherapy or irradiation). Terminally ill patients defined as patients that prior to the current hospitalization are expected to live < 6 months (as assessed by the physician responsible for the patient). Known active acute or chronic viral infections, e.g. Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV) or other chronic infection. Known severe chronic respiratory health problems with severe pulmonary hypertension (≥40 mmHg) or respirator dependency. Known active upper gastrointestinal (GI) tract ulceration or hepatic dysfunction including but not limited to: biopsy-proven cirrhosis; portal hypertension; episodes of past upper GI bleeding attributed to portal hypertension; or prior episodes of hepatic failure, encephalopathy, or coma. Known New York Heart Association (NYHA) class IV heart failure or unstable angina, ventricular arrhythmias, active ischemic heart disease, or myocardial infarction within six months prior to diagnosis of sepsis. 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: 85 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: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: One Dose: 3 Sepsis patients will be treated with Allocetra-OTS, following safety assessment additional 3 patients will be treated (total 6 patients). Two doses: Once safety is established 4 sepsis patients will be treated with 2 doses of Allocetra-OTS; The first, as in the first six patients and the second 48 hr following the first treatment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allocetra-OTS<br>Standard of Care (SOC) Drug: One dose Allocetra-OTS 140 140x106 /kg | Biological: Allocetra-OTS<br>* Allocetra-OTS contains allogeneic donor mononuclear enriched cells in the form of a liquid suspension with at least 40% early apoptotic cells. The suspension is prepared with Ringer's lactate solution.<br>|
| Experimental: Allocetra-OTS Two doses<br>Standard of Care (SOC) Drug: Two doses Allocetra-OTS 140 140x106 /kg | Biological: Allocetra-OTS<br>* Allocetra-OTS contains allogeneic donor mononuclear enriched cells in the form of a liquid suspension with at least 40% early apoptotic cells. The suspension is prepared with Ringer's lactate solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of safety by determining the number of participants with any Adverse Events (AE),Serious Adverse Events (SAE) and fatal SAE | Incidence rates of any Adverse Events (AE), Serious Adverse Events (SAE) and fatal SAE | 28 days follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Organ function or support measurements | Ventilator-free days, and/or Vasopressor-free days, and/or Days without renal replacement therapy (dialysis) and/or days with creatinine ≤ baseline +20%, and/or Days with ≥ 100x109/L platelets count, and/or Days with ≤ three times normal ALT (Alanine transaminase) and AST ••(Aspartate Aminotransferase) levels and/or ≤ two times normal bilirubin levels and/or Days with return to GCS (Glasgow Coma Scale) 15 | 28 days follow up | 
| Mortality | Incidence rate of Moratlity from any cause | 28 days follow up | 
| Hospitalization | Cumulative days in Intensive care unit (ICU) or Intermediate Care Units (IMU) and/or in hospital. | 28 days follow up | 
| CRP | Time to C-reactive protein (CRP) < 20 mg/L. | 28 days follow up | 
| Lactate levels | Time to normal + 20% lactate levels | 28 days follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allocetra-OTS, Cell based therapy, Apoptotic cells