1. Sepsis
Conditions
Interventions
Allocetra-OTS is a cell-based therapeutic composed of allogeneic healthy donor
mononuclear enriched cells, brought to an apoptotic state. Allocetra-OTS is
provided in cryopreservation bags, each con
Sponsors
Enlivex Therapeutics R&D Ltd;
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female >=18 years and =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. 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.
Exclusion criteria
Exclusion criteria: 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 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 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy: Change from baseline in SOFA score throughout 28 days. Safety: Number and severity of AEs and Serious Adverse Events (SAEs) throughout 28 days follow up period. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Ventilator-free days over 28 days - Vasopressor-free days over 28 days - Days without renal replacement therapy (dialysis) - Time in ICU and time in hospital - Number of days with creatinine | — |
Countries
Netherlands
Outcome results
None listed