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

1. Male or female >=18 years and <=90 years of age.
2. Diagnosis of Sepsis meeting Sepsis 3 criteria, defined by the presence of
organ dysfunction as identified by a total SOFA score >=5 points above
pre-admission (pre-illness) SOFA. Patients in septic shock with SOFA score up
to 13 may be included.
3. Initiation of antibiotics treatment for the suspected infection causing
sepsis.
4. Sepsis due to infection in at least one of the below organs:
4.1. Suspected, presumed or documented Community-Acquired Pneumonia (CAP).
4.2 Urinary tract infection/urosepsis
4.3. Acute cholecystitis
4.4. Acute cholangitis
4.5. Other Intra-Abdominal Infections (IAI)
4.6. Skin or soft tissue infection
5. Adequate infectious source control if necessary as determined by the
investigator, or source control is scheduled to be completed prior to IP
administration. In case source control will not be completed prior to IP
administration, Sponsor pre-approval is required for IP administration.
6. Signed written informed consent by the patient, or consent obtained
according to local regulations if the patient is unable to provide informed
consent.
7. Women of childbearing potential and all men must agree to use 2 methods of
an adequate contraception: One barrier method (e.g. diaphragm, or condom or
sponge, each of which are to be combined with a spermicide) and one hormonal
method (e.g. oral, transdermal patch, implanted contraceptives or intrauterine
device) prior to study entry and for the duration of study participation
through 4 weeks following IP administration. Subjects that are highly unlikely
to conceive (e.g. surgically sterile, postmenopausal, or not heterosexually
active) are exempt.
Non-childbearing potential is defined as (by other than medical reasons):
>=45 years of age and has not had menses for over 2 years.
<45 years of age and amenorrhoeic for > 2 years without a hysterectomy and
oophorectomy and a Follicle Stimulating Hormone (FSH) value in the
postmenopausal range upon pre-trial (screening) evaluation.
For women, post hysterectomy, bilateral oophorectomy, bilateral salpingectomy
or bilateral tubal ligation and vasectomy for men at least 6 weeks prior to
screening. Documented hysterectomy or oophorectomy must be confirmed with
medical records of the actual procedure or confirmed by ultrasound. Tubal
ligation must be confirmed with medical records of the actual procedure.

1. Sepsis due to infection other than lung infection, UTI, IAI, skin/soft
tissue infection or sepsis patients where site of infection is unclear or
unknown.
2. Patients on chronic dialysis.
3. Patients with acute pancreatitis (serum amylase > 3 ULN with clinical
abdominal pain).
4. Moribund patients at a high risk of death within 48 hours of treatment.
5. Weight < 50 kg of >120 kg or Body Mass Index (BMI) > 40 kg/m2.
6. SOFA score >= 14 at screening.
7. Patients with risk of nosocomial infection due to hospitalization or surgery
within 30 days prior to diagnosis of sepsis.
8. A known malignancy that is progressing or has required active treatment
within the past 3 months.
9. 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).
10. Known active symptomatic 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.
11. Chronic respiratory disease requiring home oxygen therapy on a regular
basis for > 6 h/day.
12. 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.
13. Known New York Heart Association (NYHA) class IV heart failure or unstable
angina, ventricular arrhythmias, acute coronary disease, or myocardial
infarction within six months prior to diagnosis of sepsis.
14. Known immunocompromised state or medications known to be immunosuppressive
as follows:
• Hydrocortisone (for the treatment of septic shock) > 300 mg /d
• Cyclophosphamide in the last 60 days;
• Chemotherapy in the last 3 months;
• Anti-tumor necrosis factor (TNF) agents, interleukin (IL)-1 receptor
antagonists (IL-1-RA), CTLA-4 fusion proteins, anti-CD20, anti-CD52, anti-IL-2,
anti-IL-6R, anti-IL-12/23, or integrin inhibitor agents within the last 8 weeks.
15. Organ allograft or previous history of stem cell transplantation.
16. Women who are pregnant or breastfeeding. Child-bearing potential females
must have a negative serum ß-hCG or hCG blood test at screening. Pregnancy
testing is not required for postmenopausal or surgically sterilized women.
17. Known hypersensitivity to any component of study treatment or excipients.
18. Participation in an interventional investigational study within 30 days
prior to diagnosis of sepsis.
19. 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).