study to assess the safety, tolerability, and preliminary efficacy of st266 in infants with necrotizing enterocolitis

Conditions: Necrotizing Enterocolitis

Summary: the primary objective of this study is to determine the safety and tolerability of two dose levels (0.5 ml/kg and 1.0 ml/kg) of once daily (qd) via iv route of administration of st266 in treating patients with bell's stage iia or higher medical nec by incidence of treatment emergent adverse events (teaes) and saes, with a secondary objective to assess preliminary efficacy of the same two dose levels (0.5 ml/kg and 1.0 ml/kg) of qd via iv route of administration of st266 in treating patients with bell's stage iia or higher medical nec.

this phase 1-2 clinical trial is a randomized, controlled, open-label study using a sequential cohort design. assignment to cohorts will be based on the following dosages and weight ranges: 0.5 ml/kg and 1.0 ml/kg; weight ≥1000 g and ≤3000 g, and weight ≥800 g and ≤999 g. in each cohort, patients will be randomized to either st266 + soc or soc alone. the first 3 patients randomized to st266 will be staggered, where each patient must complete their 10 day treatment cycle and 1 month follow up visit and be evaluated by the data safety monitoring board (dsmb), before dosing of the next patient occurs. patients randomized to soc alone will follow the treatment plan as dictated by the investigator or licensed medical designee and will be evaluated for the same inclusion/exclusion criteria and selected endpoints for analysis. if for any reason a patient is withdrawn, the decision for replacement will be determined by the dsmb. dosing for the next cohort will occur after review of safety data up to and including day 28/1 month from all patients in the previous cohort. the dsmb reviews will include comprehensive safety data analysis of data available at that time.

Eligibility criteria:
inclusion criteria: 1. infants born from ≥26 weeks gestational age to 40 weeks gestational age; up to 40 weeks postmenstrual gestational age (gestational age plus chronological age in terms of weeks) with current weight at diagnosis of nec between ≥800g and ≤3000g as a result of prematurity and/or iugr. parent(s)/legal medical representative(s) voluntarily provides written consent prior to study enrollment. 2. minimum bell stage iia nec diagnosis by radiologic confirmed pneumatosis intestinalis and may include intestinal dilation and ileus. exclusion criteria: 1. infants with abdominal perforation at less than 10 days of life 2. not expected to survive ≥2 weeks or born with a lethal condition requiring hospice or palliative care (e.g., disease has progressed to nec totalis, or patient has multi-organ system failure). 3. born with major congenital anomalies such as cardiac defects (e.g., tetralogy of fallot) or chromosomal disorders/anomalies (e.g., neural tube defect). 4. mother's receipt of any investigational product during pregnancy. 5. infants with malignancies (e.g., neoplastic cell growth as a solid tumor or a blood neoplasm, such as congenital leukemia). 6. infants with hypercoagulability disorders (any active thrombosis, diagnosis of disseminated intravascular coagulation or other acquired/inherited disorders (i.e., hemophilia) of coagulation. 7. infants with a known immunodeficiency (such as galactosemia or agranulocytosis). 8. infants with anatomic defects that require surgical intervention. 9. infants with persistent pulmonary hypertension of newborn. 10. infants with any congenital or acquired gastrointestinal pathology that preclude feeds within 7 days after birth (e.g., duodenal atresia). 11. infants who have hypoxic ischemic injury (perinatal asphyxia). 12. infants with polycythemia (at time of treatment) (\>22 g/dl). 13. positive maternal human immunodeficiency virus status. 14. history of maternal drug abuse (such as amphetamines, opiates, cocaine). this does not include marijuana, or prescription medications for treatment of drug abuse. 15. considered by the investigator, for any reason, to be an unsuitable candidate for the study. 16. infants diagnosed with nec who will require immediate surgical intervention.

Keywords: necrotizing enterocolitis nec