Sepsis MedDRA version: 20.0 Level: PT Classification code 10040047 Term: Sepsis System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Allocetra-OTS cells in Ringer's Lactate Solution
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Allogeneic peripheral blood mononuclear cells induced to apoptotic state
Sponsors
Enlivex Therapeutics R&D Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female =18 years and =90 years of age. 2. Suspected, presumed or documented community-acquired pneumonia by imaging. 3. Treatment with antibiotics after at least one course for the suspected infection. 4. Meets Sepsis 3 criteria: the presence of organ dysfunction as identified by a total SOFA score =2 points above pre-admission SOFA. 5. Signed written informed consent by the patient, or his/her legal guardian or delayed patient consent (based on local regulations). 6. 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. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 67 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 93
Exclusion criteria
Exclusion criteria: 1. Sepsis due to infection other than lung infection, or sepsis patients where site of infection is unclear or unknown. 2. On chronic dialysis. 3. Invasive ventilated patient and PaO2/FiO2 120 kg or Body Mass Index (BMI) >40 kg/m2. 5. SOFA score = 10 at screening (Day -1). 6. Patients with Septic shock; requiring persisting hypotension treated with vasopressors to maintain MAP =65 mmHg AND having a serum lactate level >4 mmol/L (36 mg/dL) despite adequate volume resuscitation at screening and on Day 1 prior to IP administration. 7. Surgical intervention within 30 days prior to diagnosis of sepsis, plan for surgical intervention (not including percutaneous procedure needed for the current treatment of the sepsis and its complications such as chest drain, Peripherally Inserted Central Catheter (PICC) line or central line insertion among others). 8. Patients with risk of nosocomial infection due to hospitalization within 30 days prior to diagnosis of sepsis. 9. A known malignancy that is progressing or has required active treatment within the past 3 months. 10. Patient with end-stage disease (unrelated to sepsis) defined as patients who prior to the current hospitalization are expected to live 6 h/day. 13. Known active upper gastrointestinal (GI) tract ulceration or hepatic dysfunction including but not limited to biopsy-proven cirrhosis; Endstage 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. 14. 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. 15. Known immunocompromised state or medications known to be immunosuppressive as follows: • Hydrocortisone (for the treatment of septic shock) > 300 mg /d Prednisone or equivalent to a dose =10 mg/day, for more than 14 days within the last 28 days. • Methotrexate, cyclophosphamide, cyclosporine A (unless as ophthalmic formulation), leflunomide/teriflunomide (unless as monotherapy), tacrolimus (unless as a topical formulation), sirolimus, everolimus, temsirolimus, mycophenolate mofetil or azathioprine, in the last 60 days; • Chemotherapy in the last 3 months; • Mycophenolate mofetil (MMF) or sirolimus for solid organ transplant or bone marrow transplant with no time limitation. • Thalidomide within the last 72 hours. • 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, anti-B-cell activation factor (BAFF) or integrin inhibitor agents within the last 8 weeks. 16. Organ allograft or previous history of stem cell transplantation. 17. 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. 18. Participation in an interventional inve
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to compare the safety and efficacy of different doses and regimens of Allocetra-OTS to that of Placebo in the treatment of organ failure in adult sepsis patients;Secondary Objective: To compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients and assess long term safety follow up;Primary end point(s): 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.;Timepoint(s) of evaluation of this end point: 28 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Ventilator-free days over 28 days Vasopressor-free days over 28 days All-cause mortality at Day 28 following first dose Days without renal replacement therapy (dialysis) (evaluation up to 12 months) Time in ICU and time in hospital (evaluation up to 12 months) Number of days with creatinine = Baseline levels +20% (evaluation up to 12 months) Changes from baseline in C-reactive protein (CRP) levels (evaluation up to 12 months) Detection of autoimmune and human leukocyte antigen (HLA) antibodies (evaluation up to 12 months) Number and severity of AEs and SAEs throughout 12 months follow-up period (evaluation up to 12 months);Timepoint(s) of evaluation of this end point: 28 days and throughout 12 months follow-up period | — |
Countries
Belgium, France, Greece, Israel, Italy, Netherlands, Spain
Contacts
Public ContactRegulatory unit
Accelsiors CRO and Consultancy Services Ltd.
Outcome results
None listed