Prevention of Sepsis-related Organ Dysfunction With Allocetra-OTS (P-SOFA-1)

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.

Study Overview

• Status: Completed
• Conditions: Organ Dysfunction Syndrome Sepsis
• Intervention / Treatment: Biological: Allocetra-OTS

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel, 12000
    • Hadassah Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Allocetra-OTS; Standard of Care (SOC) Drug: One dose Allocetra-OTS 140 140x106 /kg	Biological: Allocetra-OTS; 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.
EXPERIMENTAL: Allocetra-OTS Two doses; Standard of Care (SOC) Drug: Two doses Allocetra-OTS 140 140x106 /kg	Biological: Allocetra-OTS; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Enlivex Therapeutics Ltd.
• Investigators: Study Director: Dror Mevorach, Prof, Enlivex Therapeutics LTD Email:mevorachd@gmail.com

Publications and helpful links

General Publications

• van Heerden PV, Abutbul A, Sviri S, Zlotnick E, Nama A, Zimro S, El-Amore R, Shabat Y, Reicher B, Falah B, Mevorach D. Apoptotic Cells for Therapeutic Use in Cytokine Storm Associated With Sepsis- A Phase Ib Clinical Trial. Front Immunol. 2021 Sep 30;12:718191. doi: 10.3389/fimmu.2021.718191. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 27, 2019
• Primary Completion (ACTUAL): December 10, 2019
• Study Completion (ACTUAL): January 12, 2020

Study Registration Dates

• First Submitted: April 1, 2019
• First Submitted That Met QC Criteria: April 21, 2019
• First Posted (ACTUAL): April 24, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 19, 2020
• Last Update Submitted That Met QC Criteria: May 17, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Allocetra-OTS; Cell based therapy; Apoptotic cells
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Shock; Sepsis; Toxemia; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: ENX-CL-02-001; MOH_2019-02-17_005970 (REGISTRY: Israeli Ministry of Health)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No