STARA Phase 2, Two-Stage, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of RLS-0071 in Newborns With Moderate or Severe Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia With Long-Term Follow-Up

Fecha de inicio: 27 de julio de 2023

Inclusion Criteria: 1. ≥ 36 weeks gestation. 2. Sentinel event prior to delivery such as abruption, tight nuchal cord, uterine rupture, profound bradycardia, shoulder dystocia, or cord prolapse or other acute event likely attributable for newborn depression at delivery or an acute change in the fetal status with a clinical presentation consistent with an acute sentinel event with no clearly defined etiology. 3. Moderate or severe encephalopathy based on at least one risk of encephalopathy criterion (a) and one clinical signs of encephalopathy criterion (b): 1. Risk of encephalopathy (either): * Blood gas drawn within 1 hour of birth, either arterial blood gas (ABG) or venous blood gas (VBG) (cord or infant) with pH ≤ 7.0 OR base deficit ≥ 16 mmol/L. OR * appearance, pulse, grimace, activity, and respiration (APGAR) score ≤ 5 at 10 minutes OR * The infant required assisted ventilation ≥ 10 minutes after birth (ie, endotracheal, mask ventilation, or continuous positive airway pressure \[CPAP\]). 2. Clinical signs of encephalopathy (either/both): * Moderate/Severe encephalopathy on National Institute of Child Health and Human Development assessment. * Evidence of seizures (clinical and/or electroencephalogram). 4. Be eligible to receive therapeutic hypothermia. 5. Active whole-body cooling to be started prior to 6 hours of age (passive cooling is permitted prior to active whole body cooling). 6. Product of a singleton pregnancy. 7. Written informed consent obtained from parent or legal guardian. Exclusion Criteria: 1. Inability to enroll in the study and initiate the first dose of RLS-0071 within 10 hours of life. 2. Known major congenital and/or chromosomal abnormality(ies). 3. Severe growth restriction (birth weight ≤ 1800 g). 4. Prenatal diagnosis of brain abnormality or hydrocephalus. 5. Patient's head circumference is \< 30 cm. 6. 10-minute APGAR score \< 2, if available. 7. Infants suspected of overwhelming sepsis or congenital infection based on the Investigator's clinical consideration at the time of enrollment. 8. Persistent severe hypotension unresponsive to inotropic support (requiring \>2 inotropes, not inclusive of hydrocortisone). 9. Persistent severe hypoxia in the setting of 100% fraction of inspired oxygen (FiO₂) and unresponsive to nitric oxide or requiring extracorporeal membrane oxygenation (ECMO). 10. Severe disseminated intravascular coagulation with clinical bleeding. 11. Neonatal encephalopathy believed to be due to a cause other than perinatal hypoxia (ie, other than HIE). 12. Moribund infants for whom withdrawal of care being considered. 13. Suspected or confirmed fetal alcohol syndrome or suspected substance withdraw seizures. 14. Any other condition that the investigator may consider would make the patient ineligible for the study or place the patient at an unacceptable risk (Note: this criterion would include a clinically significant \[eg, Grade 3 or 4\] intracranial hemorrhage).