Clinical trial NCT06315738: Study to Assess the Safety, Tolerability, and Preliminary Efficacy of ST266 in Infants With Necrotizing Enterocolitis
Official title: Randomized, Controlled, Phase 1-2 Open Label Study of ST266 IV Administration to Assess the Safety, Tolerability, and Preliminary Efficacy of ST266 in Infants With Necrotizing Enterocolitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Necrotizing Enterocolitis
Keywords: Necrotizing Enterocolitis
NEC
Lead sponsor: Noveome Biotherapeutics, formerly Stemnion
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2024-03-18
Enrollment: 36
Sex: ALL
Minimum age (years): 2
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 If for any reason a patient is withdrawn, the decision for replacement will be determined by the DSMB.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.

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.

Primary outcomes:
measure: Safety and Tolerability endpoint: incidence of adverse events
timeFrame: From date of randomization through 24 months of age
measure: Safety and Tolerability endpoint: incidence of serious adverse events
timeFrame: From date of randomization through 24 months of age
measure: Safety and Tolerability endpoint: Changes in labs and vitals relative to disease progression
timeFrame: From date of randomization through 24 months of age
Secondary outcomes:
measure: Efficacy endpoint: Time to pneumatosis resolution
timeFrame: From date of NEC diagnosis until resolved, up to 10 days
measure: Efficacy endpoint: Time to full enteral nutrition assessment
timeFrame: From date of completion of antibiotics and/or IP treatment until full feeding tolerance reached, 3-5 days
measure: Efficacy endpoint: Incidence of abdominal surgical intervention
timeFrame: Assessed from Day 1/Baseline visit through 24 months of age
measure: Efficacy endpoint: Change in Neonatal Sequential Organ Failure Assessment (nSOFA) score
timeFrame: From Randomization/Day 1 through Day 10 of treatment period (10 days).
Other outcomes:
measure: Exploratory endpoint: All cause mortality
timeFrame: From Day1/Baseline through 24 months of age
measure: Exploratory endpoint: Length of stay in the NICU
timeFrame: From Day1/Baseline until date released from NICU - through 24 months of age
measure: Exploratory endpoint: Change in weight over time
timeFrame: From Day1/Baseline through 24 months of age
measure: Exploratory endpoint: Change in length over time
timeFrame: From Day1/Baseline through 24 months of age
measure: Exploratory endpoint: Change in head circumference over time
timeFrame: From Day1/Baseline through 24 months of age
measure: Exploratory endpoint: Number of significant apnea events/day over time
timeFrame: From Day1/Baseline through 1 month follow-up visit - up to 2 months
measure: Exploratory endpoint: Number of significant bradycardia events/day over time
timeFrame: From Day1/Baseline through 1 month follow-up visit - up to 2 months
measure: Exploratory endpoint: Number of significant temperature instability events/day over time
timeFrame: From Day1/Baseline through 1 month follow-up visit - up to 2 months
measure: Exploratory endpoint: Time to return to normal bowel sounds
timeFrame: From date of NEC diagnosis until resolved, up to 10 days
measure: Exploratory endpoint: Change in serum C-reactive protein (CRP)
timeFrame: To be assessed on Day2 and Day8 during treatment period; and 2 weeks and 1 month post treatment
measure: Exploratory endpoint: Time to return to normal serum platelet count levels
timeFrame: To be assessed on Day2 and Day8 during treatment period; and 2 weeks and 1 month post treatment
measure: Exploratory endpoint: Incidence of intestinal or colonic strictures
timeFrame: From Day1/Baseline through Day28/1 month post treatment follow up visit
measure: Exploratory endpoint: Incidence of sepsis
timeFrame: From Day1/Baseline through Day 28/1 month post treatment follow up visit
measure: Exploratory endpoint: Incidence of retinopathy
timeFrame: From Day1/Baseline until resolved - through 24 months of age
measure: Exploratory endpoint: Incidence of bronchopulmonary dysplasia (BPD)
timeFrame: At 36 weeks of age and at discharge from NICU - up to 6 months
measure: Exploratory endpoint: Incidence of pulmonary hypertension (PH)
timeFrame: At 36 weeks of age and at discharge from NICU - up to 6 months
measure: Exploratory endpoint: Incidence of periventricular leukomalacia
timeFrame: From Day 1 post treatment follow up visit through 24 months of age
Locations:
city: New Haven
country: United States
facility: Yale-New Haven Hospital
state: Connecticut
city: Orlando
country: United States
facility: Orlando Health, Inc. Winnie Palmer Hospital for Women and Babies
state: Florida
city: Tampa
country: United States
facility: BayCare Health System-St. Joseph's Women's Hospital
state: Florida
city: Evanston
country: United States
facility: NorthShore University-Evanston Hospital
state: Illinois
city: Durham
country: United States
facility: Duke University Medical Center (DUMC)
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma Children's Hospital
state: Oklahoma
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Magee Womens Hospital
state: Pennsylvania
Study officials:
References: