Study to Assess the Safety, Tolerability, and Preliminary Efficacy of ST266 in Infants With Necrotizing Enterocolitis
- Conditions
- Necrotizing Enterocolitis
- Interventions
- Biological: ST266
- Registration Number
- NCT06315738
- Lead Sponsor
- Noveome Biotherapeutics, formerly Stemnion
- Brief 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.
- Detailed Description
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 If for any reason a patient is withdrawn, the decision for replacement will be determined by the DSMB.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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 36
- 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.
- Minimum Bell stage IIA NEC diagnosis by radiologic confirmed pneumatosis intestinalis and may include intestinal dilation and ileus.
- Infants with abdominal perforation at less than 10 days of life
- 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).
- Born with major congenital anomalies such as cardiac defects (e.g., Tetralogy of Fallot) or chromosomal disorders/anomalies (e.g., neural tube defect).
- Mother's receipt of any investigational product during pregnancy.
- Infants with malignancies (e.g., neoplastic cell growth as a solid tumor or a blood neoplasm, such as congenital leukemia).
- Infants with hypercoagulability disorders (any active thrombosis, diagnosis of disseminated intravascular coagulation or other acquired/inherited disorders (i.e., hemophilia) of coagulation.
- Infants with a known immunodeficiency (such as galactosemia or agranulocytosis).
- Infants with anatomic defects that require surgical intervention.
- Infants with persistent pulmonary hypertension of newborn.
- Infants with any congenital or acquired gastrointestinal pathology that preclude feeds within 7 days after birth (e.g., duodenal atresia).
- Infants who have hypoxic ischemic injury (perinatal asphyxia).
- Infants with polycythemia (at time of treatment) (>22 g/dL).
- Positive maternal human immunodeficiency virus status.
- History of maternal drug abuse (such as amphetamines, opiates, cocaine). This does not include marijuana, or prescription medications for treatment of drug abuse.
- Considered by the Investigator, for any reason, to be an unsuitable candidate for the study.
- Infants diagnosed with NEC who will require immediate surgical intervention.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 3 - lower dose active + SOC treatment vs. SOC alone in lower weight range ST266 Infants with birth weight ≥800 g and ≤999 g; 0.5 mL/kg of ST266, QD; + Standard of Care (SOC) treatment (n=6); SOC (n=3) Cohort 4 - higher dose active + SOC treatment vs. SOC alone in lower weight range ST266 Infants with birth weight ≥800 g and ≤999 g; 1.0 mL/kg of ST266, QD; + Standard of Care (SOC) treatment (n=6); SOC (n=3) Cohort 1 - lower dose active + SOC treatment vs. SOC alone in higher weight range ST266 Infants with birth weight ≥1000 g and ≤3000 g; 0.5 mL/kg of ST266, QD, + Standard of Care (SOC) treatment (n=6); SOC (n=3) Cohort 2 - higher dose active + SOC treatment vs. SOC alone in higher weight range ST266 Infants with birth weight ≥1000 g and ≤3000 g; 1.0 mL/kg of ST266, QD; + Standard of Care (SOC) treatment (n=6); SOC (n=3) Cohort 1 - lower dose active + SOC treatment vs. SOC alone in higher weight range ST266 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) Cohort 2 - higher dose active + SOC treatment vs. SOC alone in higher weight range ST266 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) Cohort 3 - lower dose active + SOC treatment vs. SOC alone in lower weight range ST266 Infants with weight at diagnosis of NEC ≥800 g and ≤999 g; 0.5 mL/kg of ST266, QD; + Standard of Care (SOC) treatment (n=6); SOC (n=3) Cohort 4 - higher dose active + SOC treatment vs. SOC alone in lower weight range ST266 Infants with weight at diagnosis of NEC ≥800 g and ≤999 g; 1.0 mL/kg of ST266, QD; + Standard of Care (SOC) treatment (n=6); SOC (n=3)
- Primary Outcome Measures
Name Time Method Safety and Tolerability endpoint: incidence of serious adverse events From date of randomization through 24 months of age Patients will be assessed for safety and tolerability of ST266 treatment given IV (two dose options: 0.5mL/kg or 1.0mL/kg) via review of serious adverse events, defined as: any event that results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or may jeopardize patient so that requires intervention to prevent prior noted outcomes (includes study drug related dose-limiting toxicities and infusion reactions)
Safety and Tolerability endpoint: Changes in labs and vitals relative to disease progression From date of randomization through 24 months of age Patients will be assessed for safety and tolerability of ST266 treatment given IV (two dose options: 0.5mL/kg or 1.0mL/kg) by evaluating clinically significant changes in labs and vitals as to relatedness to disease progression and study drug effects, including assessment of vital signs (temperature, systolic and Mean arterial blood pressure (mmHg), respiratory rate, heart rate, and percent oxygen saturation as measured by pulse oximetry as noted in The Harriet Lane Handbook, 21st ed., 2018), and hematology and chemistry lab tests, which will be measured against standard laboratory acceptable ranges for premature infants.
Safety and Tolerability endpoint: incidence of adverse events From date of randomization through 24 months of age Patients will be assessed for safety and tolerability of ST266 treatment given IV (two dose options: 0.5mL/kg or 1.0mL/kg) via review of treatment emergent adverse events (TEAEs). AEs are defined as per the International Neonatal Consortium (INC) neonatal AE severity scale (NAESS): Mild, Moderate, Severe, Life Threatening, Death. Relatedness to study drug (ST266) will also be assessed.
- Secondary Outcome Measures
Name Time Method Efficacy endpoint: Time to full enteral nutrition assessment From date of completion of antibiotics and/or IP treatment until full feeding tolerance reached, 3-5 days Defined as no longer receiving total parenteral nutrition (TPN)
Efficacy endpoint: Change in Neonatal Sequential Organ Failure Assessment (nSOFA) score From Randomization/Day 1 through Day 10 of treatment period (10 days). nSOFA score is a neonatal sequential organ failure assessment of three organ systems: respiratory score criteria (range: 0-8); cardiovascular score criteria (range: 0-4); and Hematologic score criteria (range: 0-3) with a total score range: 0 (best) to 15 (worst)
Efficacy endpoint: Time to pneumatosis resolution From date of NEC diagnosis until resolved, up to 10 days Pneumatosis is considered resolved when no longer observed on abdominal x-ray
Efficacy endpoint: Incidence of abdominal surgical intervention Assessed from Day 1/Baseline visit through 24 months of age Abdominal surgical intervention defined as laparotomy, including drain placement
Trial Locations
- Locations (7)
Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
University of Pittsburgh Medical Center Magee Womens Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Orlando Health, Inc. Winnie Palmer Hospital for Women and Babies
🇺🇸Orlando, Florida, United States
BayCare Health System-St. Joseph's Women's Hospital
🇺🇸Tampa, Florida, United States
NorthShore University-Evanston Hospital
🇺🇸Evanston, Illinois, United States
Duke University Medical Center (DUMC)
🇺🇸Durham, North Carolina, United States
Oklahoma Children's Hospital
🇺🇸Oklahoma City, Oklahoma, United States