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 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 If for any reason a patient was withdrawn, the decision for replacement was determined by the DSMB.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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
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.
Arkansas Children's Hospital
Little Rock, Arkansas, United States
RECRUITINGUniversity of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
RECRUITINGYale-New Haven Hospital
New Haven, Connecticut, United States
RECRUITINGBayCare Health System-St. Joseph's Women's Hospital
Tampa, Florida, United States
RECRUITINGNorthShore University-Evanston Hospital
Evanston, Illinois, United States
RECRUITINGOklahoma Children's Hospital
Oklahoma City, Oklahoma, United States
RECRUITINGPenn State Health Milton S Hershey Medical Center/Penn State University College of Medicine
Hershey, Pennsylvania, United States
RECRUITINGUniversity of Pittsburgh Medical Center Magee Womens Hospital
Pittsburgh, Pennsylvania, United States
RECRUITINGSafety 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.
Time frame: From date of randomization through 24 months of age
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)
Time frame: From date of randomization through 24 months of age
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.
Time frame: From date of randomization through 24 months of age
Efficacy endpoint: Time to pneumatosis resolution
Pneumatosis is considered resolved when no longer observed on abdominal x-ray
Time frame: From date of NEC diagnosis until resolved, up to 10 days
Efficacy endpoint: Time to full enteral nutrition assessment
Defined as no longer receiving total parenteral nutrition (TPN)
Time frame: From date of completion of antibiotics and/or IP treatment until full feeding tolerance reached, 3-5 days
Efficacy endpoint: Incidence of abdominal surgical intervention
Abdominal surgical intervention defined as laparotomy, including drain placement
Time frame: Assessed from Day 1/Baseline visit through 24 months of age
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)
Time frame: From Randomization/Day 1 through Day 10 of treatment period (10 days).
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