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
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
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.
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).
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).