A 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

This is a Phase 2, two-stage, multisite, randomized, double-blind, placebo-controlled, multiple-ascending dose study of RLS-0071 to assess the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy in newborns with moderate or severe HIE undergoing therapeutic hypothermia. In Stage 1, participants will receive either ascending doses of RLS-0071 or a matched volume of placebo for 72 hours in addition to standard of care treatment, including therapeutic hypothermia. During and after the dosing period, participants will be monitored and assessed for safety evaluations through Day 14. After completion of Stage 1, participants will transition to Stage 2 of the study for long-term observation until participants reach 24 months of age. The first cohort subsets, consisting of Cohort 1a (moderate HIE) and 1b (severe HIE), will receive a dose of 3 mg/kg RLS-0071 or a matched volume of placebo every 8 hours (q8h). A Data Safety Monitoring Board (DSMB) will review available clinical safety and PK data from Cohort 1 subsets with completed study intervention, and make a recommendation on whether to escalate the dose for moderate and severe HIE cohorts. The Sponsor will consider the DSMB recommendation to make their decision on dose escalation in addition to their own evaluation of all available safety and PK data. If the decision is made to escalate, Cohort 2 subsets (2a \[moderate\] and 2b \[severe\]) will be recruited to receive an escalated dose of RLS-0071 (10 mg/kg) or a matched volume of placebo. Following the completion of study intervention for each Cohort 2 subset (2a \[moderate\] or 2b \[severe\]), the DSMB will review available safety and PK data and make a recommendation whether to expand enrollment for Cohort 2+ (2a+ \[moderate\] or 2b+ \[severe\]) at 10 mg/kg RLS-0071 or a matched volume of placebo.