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

• ClinicalTrials.gov Identifier: NCT04612413
• Recruitment Status: Not yet recruiting
• First Posted: November 3, 2020
• Last Update Posted: November 4, 2020
• Sponsor: Enlivex Therapeutics Ltd.
• Collaborator: Cato Research
• Information provided by (Responsible Party): Enlivex Therapeutics Ltd.

Study Description

Brief Summary:

A phase II, multi-center (approximately 10 sites in Israel), randomized, placebo-controlled, dose- finding study comparing the efficacy, safety and tolerability of different dosing regimens of Allocetra-OTS, in up to 160 adult sepsis patients with organ sysfunction.

Condition or disease	Intervention/treatment	Phase
Sepsis; Community-acquired Pneumonia; Organ Dysfunction Syndrome	Drug: ALLOCETRA-OTS; Other: Placebo	Phase 2

Detailed Description:

Up to 160 eligible patients will be allocated in a 1:1:1:1 ratio between the 4 cohorts (up to 40 patients in each cohort). Randomization will be in a double blinding fashion which will be kept until Day 4 followed by a single blinding until the end of the study.

Randomization will be stratified by screening Sequential Organ Failure Assessment (SOFA) score (2-6 vs. 7-9).

Patients will be followed over 28 days for efficacy and continue safety follow up of 12 months from IP administration.

Patients participating in this study, regardless if hospitalized or discharged, will be followed daily through Day 7 (inclusive, short-term follow-up), then on Days 10 (only for patients receiving 2nd dose), Day 14, and Day 28 (medium-term follow-up), , and then at 3 months, 6 months and 12 months (long-term safety follow-up).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention Model Description

Up to 160 patients will be allocated in a 1:1:1:1 ratio between the 4 cohorts :

Placebo Single Intravenous (IV) dose of Allocetra-OTS, 5x109 cells Single IV dose of Allocetra-OTS, 10x109 cells Single or two IV doses of Allocetra-OTS, 10x109 cells in each dose

• Masking: Double (Participant, Investigator)
• Masking Description: Randomization will be in a double blinding fashion which will be kept until study Day 4 followed by a single blinding until the end of the study.
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: November 15, 2020
• Estimated Primary Completion Date: January 31, 2022
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Cohort 1; 375 ml Ringer's lactate solution	Other: Placebo; Ringer's Lactate Solution
Experimental: Cohort 2; Single IV dose of Allocetra-OTS contain 5x10^9 cells	Drug: ALLOCETRA-OTS; The product contains allogeneic donor mononuclear enriched cells in the form of a liquid suspension containing early apoptotic cells.; Other Name: Cell based therapy, apoptotic cells
Experimental: Cohort 3; Single IV dose of Allocetra-OTS contain 10x10^9 cells	Drug: ALLOCETRA-OTS; The product contains allogeneic donor mononuclear enriched cells in the form of a liquid suspension containing early apoptotic cells.; Other Name: Cell based therapy, apoptotic cells
Experimental: Cohort 4; Single or two IV doses of Allocetra-OTS contain 10x10^9 cells in each dose	Drug: ALLOCETRA-OTS; The product contains allogeneic donor mononuclear enriched cells in the form of a liquid suspension containing early apoptotic cells.; Other Name: Cell based therapy, apoptotic cells

Outcome Measures

Primary Outcome Measures :

1. To compare the safety of different doses and regimens of Allocetra-OTS to that of Placebo in the treatment of organ failure in adult sepsis patients [ Time Frame: 28 days ]
   Number and severity of AEs and SAEs throughout 28 days follow up period
2. To compare the efficacy of different doses and regimens of Allocetra-OTS to that of Placebo in the treatment of organ failure in adult sepsis patients [ Time Frame: 28 days ]
   Change from baseline in SOFA score throughout 28 days

Secondary Outcome Measures :

1. compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients [ Time Frame: 28 days ]
   Vasopressor-free days over 28 days.
2. compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients. [ Time Frame: 28 days ]
   Ventilator-free days over 28 days
3. compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients [ Time Frame: 28 days ]
   Days without renal replacement therapy (dialysis).
4. compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients [ Time Frame: 28 days ]
   Time in ICU and time in hospital
5. compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients [ Time Frame: 28 days ]
   Number of days with creatinine ≤ Baseline levels +20%.
6. compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients [ Time Frame: 28 days ]
   All-cause mortality at Day 28 following first dose
7. compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients [ Time Frame: 28 days ]
   Changes in CRP levels
8. Assess long term safety follow up [ Time Frame: 12 months ]
   Number and severity of AEs and Serious Adverse Events (SAEs) throughout 12 months follow up period

Eligibility Criteria

• Ages Eligible for Study: 45 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female ≥45 years and ≤85 years of age.
• Suspected, presumed or documented community-acquired pneumonia by imaging.
• Treatment with antibiotics after at least one course for the suspected infection.
• Meets Sepsis 3 criteria: the presence of organ dysfunction as identified by a total SOFA score ≥2 points above pre-admission SOFA.
• Has at least one respiratory SOFA score and at least one additional SOFA in any other organ.
• Signed written informed consent by the patient, or his/her legal guardian or delayed patient consent (based on MOH guidelines and local Ethics Committee (EC) approval).
• Child-bearing potential Females must not be lactating or pregnant at Screening, as documented by a negative Beta-Human Chorionic Gonadotropin (ß-hCG) or Human Chorionic Gonadotropin (hCG) blood test.
• Women of child-bearing potential or males whose partners are women of child-bearing potential, use an effective method of contraception throughout the trial.

Exclusion Criteria:

• Sepsis due to infection other than lung infection, or sepsis patients where site of infection is unclear or unknown
• On chronic dialysis.
• Invasive ventilated patient with PaO2/FiO2 < 100 mmHg
• Weight <50 kg or >120 kg or Body Mass Index (BMI) >40 kg/m2.
• SOFA score ≥ 10 at screening (Day -1).
• Septic shock defined by persisting hypotension requiring vasopressors to maintain MAP ≥65 mmHg and having a serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation at screening and on Day 1 prior to IP administration.
• Surgical intervention, plan for surgical intervention (not including percutaneous procedure such as chest drain), or hospitalization within 30 days prior to diagnosis of sepsis.
• A known malignancy that is progressing or has required active treatment within the past 3 months.
• Patient with end-stage disease (unrelated to sepsis) defined as patients who prior to the current hospitalization are expected to live < 6 months (as assessed by the study physician).
• Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or chronic viral infections, such as, Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV) or other chronic infections.
• Chronic respiratory disease requiring home oxygen therapy on a regular basis for > 6 h/day.
• Known active upper Gastrointestinal (GI) tract ulceration or hepatic dysfunction including but not limited to biopsy-proven cirrhosis; End-stage cirrhosis (Child Pugh Class C); 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.
• Participation in an interventional investigational study within 30 days prior to diagnosis of sepsis.
• Likely to be non-compliant or uncooperative during the study (e.g. substance abuse such as drug or alcohol abuse, uncontrolled psychiatric disorder or any chronic condition that may interfere with study conduct).

Contacts and Locations

Contacts

Contact: Odelia Ben Shitrit, MBA; 972-548887609; odelia@enlivexpharm.com

Contact: Naama Kama; 972523466908; naama@enlivexpharm.com

Sponsors and Collaborators

Enlivex Therapeutics Ltd.

Cato Research

Investigators

• Principal Investigator: Pierre Singer, MD; Rabin medical center, Belinson Campus, Petah Tiqwa Isarel

More Information

• Responsible Party: Enlivex Therapeutics Ltd.
• ClinicalTrials.gov Identifier: NCT04612413
• Other Study ID Numbers: ENX-CL-02-002
• First Posted: November 3, 2020
• Last Update Posted: November 4, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Sepsis; Toxemia; Pneumonia; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Infection; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes