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

Necrotizing Enterocolitis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06315738
• Other study ID #: ST266-NEC-201
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 29, 2024
• Est. completion date: August 2027

Study information

• Verified date: April 2024
• Source: Noveome Biotherapeutics, formerly Stemnion
• Contact: Karin Potoka, MD
• Phone: 412-512-1446
• Email: kpotoka[@]noveome.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 If for any reason a patient is withdrawn, the decision for replacement will be determined by the DSMB.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

• Status: Recruiting
• Enrollment: 36
• Est. completion date: August 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Weeks to 8 Weeks

Eligibility

Inclusion Criteria:

1. Premature (=26 and =36 weeks gestational age) infant weight between =800g and =3000g. 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.

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.

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.

15. Considered by the Investigator, for any reason, to be an unsuitable candidate for the study.

Related Conditions & MeSH terms

• Enterocolitis
• Enterocolitis, Necrotizing
• Necrotizing Enterocolitis

Intervention

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.

Locations

Country	Name	City	State
United States	Duke University Medical Center (DUMC)	Durham	North Carolina
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

Sponsors (2)

Lead Sponsor	Collaborator
Noveome Biotherapeutics, formerly Stemnion	Parexel

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory endpoint: All cause mortality	Assessment of all deaths that occurred during the study	From Day1/Baseline through 6 month follow up visit - up to 6 months
Other	Exploratory endpoint: Length of stay in the NICU	Defined as total number of days from Day1/Baseline until date released from NICU	From Day1/Baseline until date released from NICU - up to 6 months
Other	Exploratory endpoint: Change in weight over time	Weight will be measured in grams (g)	From Day1/Baseline through 6 month follow-up visit - up to 6 months
Other	Exploratory endpoint: Change in length over time	Length will be measured in centimeters (cm)	From Day1/Baseline through 6 month follow-up visit - up to 6 months
Other	Exploratory endpoint: Change in head circumference over time	Circumference will be measured in centimeters (cm) and will be used to ensure normal head growth.	From Day1/Baseline through 6 month follow-up visit - up to 6 months
Other	Exploratory endpoint: Number of significant apnea events/day over time	Significant apnea: any apnea for greater than 20 seconds	From Day1/Baseline through 1 month follow-up visit - up to 2 months
Other	Exploratory endpoint: Number of significant bradycardia events/day over time	Significant bradycardia: any bradycardia heart rate < 70BPM for > 6 seconds	From Day1/Baseline through 1 month follow-up visit - up to 2 months
Other	Exploratory endpoint: Number of significant temperature instability events/day over time	Significant temperature instability event: temperature < 36.5C or > 37.5C outside neutral/thermal environment or requires a change in isolette temperature outside of standard protocol	From Day1/Baseline through 1 month follow-up visit - up to 2 months
Other	Exploratory endpoint: Time to return to normal bowel sounds	Defined as are typically soft and gurgling, indicating pneumatosis resolution and no feeding intolerance, no bowel obstruction or perforation.	From date of NEC diagnosis until resolved, up to 10 days
Other	Exploratory endpoint: Change in serum C-reactive protein (CRP)	Included as part of labs being assessed per standard of care treatment	To be assessed on Day2 and Day8 during treatment period; and 2 weeks and 1 month post treatment
Other	Exploratory endpoint: Time to return to normal serum platelet count levels	Included as part of labs being assessed per standard of care treatment	To be assessed on Day2 and Day8 during treatment period; and 2 weeks and 1 month post treatment
Other	Exploratory endpoint: Incidence of intestinal or colonic strictures	Measured by fluoroscopic study (barium enema or upper gastrointestinal scope); only conducted if infant had symptoms indicating partial bowel obstruction (e.g., feeding intolerance, abdominal distension, bilious emesis).	From Day1/Baseline through Day28/1 month post treatment follow up visit
Other	Exploratory endpoint: Incidence of sepsis	Defined as presence of a pathogenic bacteria in blood culture or two positive blood cultures	From Day1/Baseline through Day 28/1 month post treatment follow up visit
Other	Exploratory endpoint: Incidence of retinopathy	To be monitored while in NICU	From Day1/Baseline until resolved - up to 6 months
Other	Exploratory endpoint: Incidence of bronchopulmonary dysplasia (BPD)	To be identified at 36 weeks CGA and at discharge from NICU	At 36 weeks of age and at discharge from NICU - up to 6 months
Other	Exploratory endpoint: Incidence of pulmonary hypertension (PH)	To be identified at 36 weeks CGA and at discharge from NICU	At 36 weeks of age and at discharge from NICU - up to 6 months
Other	Exploratory endpoint: Incidence of periventricular leukomalacia	To be measured via any form of imaging and noted if any symptoms observed	From Day 1 post treatment follow up visit through 6 month post treatment follow up visit - up to 6 months
Primary	Safety and Tolerability endpoint: incidence of adverse events	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.	From date of randomization through 6 month follow-up visit
Primary	Safety and Tolerability endpoint: incidence of serious adverse events	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)	From date of randomization through 6 month follow-up visit
Primary	Safety and Tolerability endpoint: Changes in labs and vitals relative to disease progression	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.	From date of randomization through 6 month follow-up visit
Secondary	Efficacy endpoint: Time to pneumatosis resolution	Pneumatosis is considered resolved when no longer observed on abdominal x-ray	From date of NEC diagnosis until resolved, up to 10 days
Secondary	Efficacy endpoint: Time to full enteral nutrition assessment	Defined as no longer receiving total parenteral nutrition (TPN)	From date of completion of antibiotics and/or IP treatment until full feeding tolerance reached, 3-5 days
Secondary	Efficacy endpoint: Incidence of abdominal surgical intervention	Abdominal surgical intervention defined as laparotomy, including drain placement	Assessed from Day 1/Baseline visit through 6 month follow up visit; up to 6 months
Secondary	Efficacy endpoint: Change in Neonatal Sequential Organ Failure Assessment (nSOFA) score	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)	From Randomization/Day 1 through Day 10 of treatment period (10 days).