Study to Assess the Safety, Tolerability, and Preliminary Efficacy of ST266 in Infants With Necrotizing Enterocolitis (NEC)

Purpose

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.

Condition

  • Necrotizing Enterocolitis

Eligibility

Eligible Ages
Between 2 Weeks and 8 Weeks
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Infants born from ≥22 weeks gestational age up to and including 40 weeks gestational age; up to 40 weeks postmenstrual age (gestational age plus chronological age in terms of weeks) with current weight at diagnosis of NEC between ≥500g 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. Bell's Stage IIA or higher medical NEC (Stages IIA - IIIA only) diagnosis by radiologic confirmed pneumatosis intestinalis and may include intestinal dilation and ileus. The clinician confirms NEC diagnosis by evaluation of the radiologic imaging for confirmed pneumatosis intestinalis. If X-ray is used and is equivocal, an ultrasound (US) may be used, if available, to confirm pneumatosis. If the clinician (Neonatologist and/or Pediatric Surgeon) has differing interpretation from that of the Radiologist, that should be documented in both the medical and research records for accuracy of NEC diagnosis.

Exclusion Criteria

  1. Infants with abdominal perforation. 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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Other
Cohort 1 - lower dose active + SOC treatment vs. SOC alone in higher weight range
Infants with weight at diagnosis of NEC ≥1000 g and ≤3000 g; 0.5 mL/kg of ST266, QD, + Standard of Care (SOC) treatment (n=6); SOC (n=3)
  • Biological: ST266
    Patients randomized to investigative drug product (ST266) will receive either 0.5 mL/kg or 1.0 mL/kg of ST266 QD in addition to Standard of Care treatment; Patients randomized to SOC will receive standard of care treatment only.
Other
Cohort 2 - higher dose active + SOC treatment vs. SOC alone in higher weight range
Infants with weight at diagnosis of NEC ≥1000 g and ≤3000 g; 1.0 mL/kg of ST266, QD; + Standard of Care (SOC) treatment (n=6); SOC (n=3)
  • Biological: ST266
    Patients randomized to investigative drug product (ST266) will receive either 0.5 mL/kg or 1.0 mL/kg of ST266 QD in addition to Standard of Care treatment; Patients randomized to SOC will receive standard of care treatment only.
Other
Cohort 3 - lower dose active + SOC treatment vs. SOC alone in lower weight range
Infants with weight at diagnosis of NEC ≥500 g and ≤999 g; 0.5 mL/kg of ST266, QD; + Standard of Care (SOC) treatment (n=6); SOC (n=3)
  • Biological: ST266
    Patients randomized to investigative drug product (ST266) will receive either 0.5 mL/kg or 1.0 mL/kg of ST266 QD in addition to Standard of Care treatment; Patients randomized to SOC will receive standard of care treatment only.
Other
Cohort 4 - higher dose active + SOC treatment vs. SOC alone in lower weight range
Infants with weight at diagnosis of NEC ≥500 g and ≤999 g; 1.0 mL/kg of ST266, QD; + Standard of Care (SOC) treatment (n=6); SOC (n=3)
  • Biological: ST266
    Patients randomized to investigative drug product (ST266) will receive either 0.5 mL/kg or 1.0 mL/kg of ST266 QD in addition to Standard of Care treatment; Patients randomized to SOC will receive standard of care treatment only.

Recruiting Locations

Arkansas Children's Hospital
Little Rock, Arkansas 72202
Contact:
Vikas Chowdhary, MD
501-364-1028
vchowdhary@uams.edu

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
Contact:
Vikas Chowdhary, MD
848-702-3188
vchowdhary@uams.edu

Yale-New Haven Hospital
New Haven, Connecticut 06510
Contact:
Sarah Taylor, MD
203-688-2320
sarah.n.taylor@yale.edu

BayCare Health System-St. Joseph's Women's Hospital
Tampa, Florida 33607
Contact:
Jenelle Ferry, MD
813-872-2924
jenelle.ferry@baycare.org

NorthShore University-Evanston Hospital
Evanston, Illinois 60201
Contact:
Brandy Frost, MD
773-562-7420
bfrost@northshore.org

Oklahoma Children's Hospital
Oklahoma City, Oklahoma 73104
Contact:
Hala Chaaban, MD
405-271-5215
hala-chaaban@ouhsc.edu

Penn State Health Milton S Hershey Medical Center/Penn State University College of Medicine
Hershey, Pennsylvania 17033
Contact:
Timothy Palmer, MD
717-531-8413
tpalmer@pennstatehealth.psu.edu

University of Pittsburgh Medical Center Magee Womens Hospital
Pittsburgh, Pennsylvania 15219
Contact:
Toby Yanowitz, MD
412-641-6260
yanotd@upmc.edu

More Details

NCT ID
NCT06315738
Status
Recruiting
Sponsor
Noveome Biotherapeutics, formerly Stemnion

Study Contact

Karin Potoka, MD
412-512-1446
kpotoka@noveome.com

Detailed Description

This Phase 1-2 clinical trial is a randomized, controlled, open-label study using a modified 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 ≥500 g and ≤999 g. In each cohort, patients will be randomized to either ST266 + SOC or SOC alone. In the first cohort, the first three patients randomized to ST266 were staggered, where each patient completed their 10-day treatment period containing 10 treatment cycles and Day 28/1 Month follow-up visit and were evaluated by the Data Safety Monitoring Board (DSMB), before dosing of the next patient occurred. Patients randomized to SOC alone followed the treatment plan as dictated by the Investigator site SOC procedures and were evaluated for the same inclusion/exclusion criteria and selected endpoints for analysis. If for any reason a patient was withdrawn, the decision for replacement was determined by the DSMB. Dosing for the next cohort will occur after review of safety data up to and including Day 28/1 Month post-treatment follow-up visit from all patients in Cohort 1. DSMB reviews will include comprehensive safety data analysis of data available at that time. In Cohorts 2, 3, and 4, only a single sentinel ST266-treated patient will be required to complete their 10-day treatment period containing 10 treatment cycles and Day 28/1 Month follow-up visit and be evaluated by the Data Safety Monitoring Board (DSMB), before dosing of the next patient occurs. Given that Cohort 2 shares the same weight range and Cohort 3 the same dose as Cohort 1, Cohorts 2 and 3 may be opened for enrollment in parallel. If any safety event occurs in either Cohort 2 or 3, the DSMB will promptly evaluate and determine whether to continue the study and/or reinstate patient staggering.