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

• ClinicalTrials.gov Identifier: NCT03925857
• Recruitment Status: Completed
• First Posted: April 24, 2019
• Last Update Posted: May 19, 2020
• Sponsor: Enlivex Therapeutics Ltd.
• Information provided by (Responsible Party): Enlivex Therapeutics Ltd.

Tracking Information

• First Submitted Date: April 1, 2019
• First Posted Date: April 24, 2019
• Last Update Posted Date: May 19, 2020
• Actual Study Start Date: January 27, 2019
• Actual Primary Completion Date: December 10, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 21, 2019)

Assessment of safety by determining the number of participants with any Adverse Events (AE),Serious Adverse Events (SAE) and fatal SAE [ Time Frame: 28 days follow up ]

Incidence rates of any Adverse Events (AE), Serious Adverse Events (SAE) and fatal SAE

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 24, 2019)

• Organ function or support measurements [ Time Frame: 28 days follow up ]
  • 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
• Mortality [ Time Frame: 28 days follow up ]
  Incidence rate of Moratlity from any cause
• Hospitalization [ Time Frame: 28 days follow up ]
  Cumulative days in Intensive care unit (ICU) or Intermediate Care Units (IMU) and/or in hospital.
• CRP [ Time Frame: 28 days follow up ]
  Time to C-reactive protein (CRP) < 20 mg/L.
• Lactate levels [ Time Frame: 28 days follow up ]
  Time to normal + 20% lactate levels

Original Secondary Outcome Measures (submitted: April 21, 2019)

• Organ function or support measurements [ Time Frame: 28 days follow up ]
  • 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
• Mortality [ Time Frame: 28 days follow up ]
  Moratlity from any cause
• Hospitalization [ Time Frame: 28 days follow up ]
  Cumulative days in Intensive care unit (ICU) or Intermediate Care Units (IMU) and/or in hospital.
• CRP [ Time Frame: 28 days follow up ]
  Time to C-reactive protein (CRP) < 20 mg/L.
• Lactate levels [ Time Frame: 28 days follow up ]
  Time to normal + 20% lactate levels

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Prevention of Sepsis-related Organ Dysfunction With Allocetra-OTS
• Official Title: Prevention of Sepsis-related Organ Dysfunction With Allocetra-OTS
• Brief Summary: 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: 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
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention 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)
Primary Purpose: Prevention

• Condition: Organ Dysfunction Syndrome Sepsis

Intervention

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.

Study Arms

• Experimental: Allocetra-OTS
  Standard of Care (SOC) Drug: One dose Allocetra-OTS 140 140x106 /kg
  Intervention: Biological: Allocetra-OTS
• Experimental: Allocetra-OTS Two doses
  Standard of Care (SOC) Drug: Two doses Allocetra-OTS 140 140x106 /kg
  Intervention: Biological: Allocetra-OTS

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 21, 2019): 10
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 12, 2020
• Actual Primary Completion Date: December 10, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel

Administrative Information

• NCT Number: NCT03925857
• Other Study ID Numbers: ENX-CL-02-001; MOH_2019-02-17_005970 ( Registry Identifier: Israeli Ministry of Health )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Enlivex Therapeutics Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Enlivex Therapeutics Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Enlivex Therapeutics Ltd.
• Verification Date: May 2020