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

NCT05778188 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: RLS-0071-202
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 15

Brief Summary

Hypoxic-ischemic encephalopathy (HIE) affects approximately 4,000 to 12,000 persons annually in the United States. Mortality from HIE has been reported up to 60%, with at least 25% of survivors left with significant neurocognitive disability. Despite this vital unmet medical need, no pharmacological adjunct or alternative therapy has proven beneficial in improving outcomes in neonatal HIE. RLS-0071 is a novel peptide being developed for the treatment of neonatal HIE. This study is designed to evaluate the safety and tolerability of RLS-0071 in the treatment of newborns with moderate or severe HIE.

Conditions

Hypoxic-Ischemic Encephalopathy

Keywords

Birth Asphyxia; Anoxic brain injury

Outcome Measures

Primary Outcomes (5)

• Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment group at Day 14

  Number of participants with AEs and SAEs graded between Grade 1 (mild in severity) and Grade 5 (death related to AE).

  Day 1 to Day 14

• Frequency and severity of events of special interest and SAEs by treatment group at 24 months

  Number of participants with events of special interest and SAEs graded between Grade 1 (mild in severity) and Grade 5 (death related to AE). Events of special interest are: autoimmune disorder, persistent hypotension, persistent pulmonary hypertension, acute kidney injury, major venous thrombosis, severe intracranial hemorrhage, pulmonary hemorrhage, culture proven sepsis, necrotizing enterocolitis, severe thrombocytopenia, hepatic dysfunction, hyperbilirubinemia, coagulopathy, hypocalcemia, cerebral palsy, developmental or speech delay, learning disability, and visual or hearing impairment.

  Day 1 to 24 months

• Frequency of premature discontinuation by treatment group due to AEs at Day 14

  Number of participants who prematurely discontinue from the study due to AEs

  Day 1 to Day 14

• Acute brain injury at Day 4, assessed through magnetic resonance imaging (MRI), using a standardized scoring system

  Brain injury MRI score includes scoring extent of injury across 4 domains (Grey matter, White matter/cortex, Cerebellum, and Additional). A score of 0 indicates a normal brain MRI, whereas the maximum score of 57 indicates extensive bilateral injury.

  Day 4

• Acute brain injury at Day 12, assessed through magnetic resonance imaging (MRI), using a standardized scoring system

  Brain injury MRI score includes scoring extent of injury across 4 domains (Grey matter, White matter/cortex, Cerebellum, and Additional). A score of 0 indicates a normal brain MRI, whereas the maximum score of 57 indicates extensive bilateral injury.

  Day 12

Secondary Outcomes (14)

• Composite of mortality and neurodevelopmental impairment (NDI) at 24 months

  Day 1 to 24 months

• Mortality at 3, 6, 12, 18, and 24 months

  Day 1 to 3, 6, 12, 18, and 24 months

• Number of participants with clinically significant laboratory abnormalities, events of special interest, and SAEs at 3, 6, 12, and 18 months

  Day 1 to 3, 6, 12, and 18 months

• Neurocognitive developmental outcome assessed by Bayley-4 at 24 months of age

  24 months

• Neurodevelopmental growth impact: Diagnosis of cerebral palsy at 24 months of age

  24 months

Other Outcomes (13)

• PK parameters of RLS-0071 at multiple-ascending doses: Cmax

  Day 1 to Day 5

• PK parameters of RLS-0071 at multiple-ascending doses: Ctrough

  Day 1 to Day 5

• PK parameters of RLS-0071 at multiple-ascending doses: Area under the curve

  Day 1 to Day 5

Study Arms (2)

RLS-0071

EXPERIMENTAL

Doses of RLS-0071 to be administered every 8 hours (q8h), for a total of 10 doses over 72 hours.

Drug: RLS-0071

Placebo

PLACEBO COMPARATOR

Doses of sterile saline (sodium chloride, 0.9%) to be administered every 8 hours (q8h), for a total of 10 doses over 72 hours.

Drug: Placebo

Interventions

RLS-0071 DRUG

RLS-0071 (unit strength 10 mg/mL) will be administered by infusion for a dose level of 3 or 10 mg/kg. Planned infusion duration is 10 minutes for all dose levels.

RLS-0071

Placebo DRUG

Placebo control (commercial sterile saline) will be administered by infusion at a volume matched to RLS-0071 (3 or 10 mg/kg). Planned infusion duration is 10 minutes for all matched dose levels.

Placebo

Eligibility Criteria

• Age: Up to 10 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• ≥ 36 weeks gestation.
• 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.
• Moderate or severe encephalopathy based on at least one risk of encephalopathy criterion (a) and one clinical signs of encephalopathy criterion (b):
• 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.
• 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 \[CPAP\]).
• 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).
• Be eligible to receive therapeutic hypothermia.
• Active whole-body cooling to be started prior to 6 hours of age (passive cooling is permitted prior to active whole body cooling).
• Product of a singleton pregnancy.
• Written informed consent obtained from parent or legal guardian.

You may not qualify if:

• Inability to enroll in the study and initiate the first dose of RLS-0071 within 10 hours of life.
• Known major congenital and/or chromosomal abnormality(ies).
• Severe growth restriction (birth weight ≤ 1800 g).
• Prenatal diagnosis of brain abnormality or hydrocephalus.
• Patient's head circumference is \< 30 cm.
• minute APGAR score \< 2, if available.
• Infants suspected of overwhelming sepsis or congenital infection based on the Investigator's clinical consideration at the time of enrollment.
• Persistent severe hypotension unresponsive to inotropic support (requiring \>2 inotropes, not inclusive of hydrocortisone).
• Persistent severe hypoxia in the setting of 100% fraction of inspired oxygen (FiO₂) and unresponsive to nitric oxide or requiring extracorporeal membrane oxygenation (ECMO).
• Severe disseminated intravascular coagulation with clinical bleeding.
• Neonatal encephalopathy believed to be due to a cause other than perinatal hypoxia (ie, other than HIE).
• Moribund infants for whom withdrawal of care being considered.
• Suspected or confirmed fetal alcohol syndrome or suspected substance withdraw seizures.
• 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).

Sponsors & Collaborators

• ReAlta Life Sciences, Inc.: lead
• Premier Research: collaborator

Study Sites (15)

Study Site 016

Little Rock, Arkansas, 72202, United States

RECRUITING

Study Site 013

Orange, California, 92868, United States

RECRUITING

Study Site 020

San Diego, California, 92037, United States

RECRUITING

Study Site 019

San Diego, California, 92123, United States

RECRUITING

Study Site 001

Gainesville, Florida, 32608, United States

RECRUITING

Study Site 018

Miami, Florida, 33143, United States

RECRUITING

Study Site 010

Orlando, Florida, 32803, United States

RECRUITING

Study Site 014

Indianapolis, Indiana, 46202, United States

RECRUITING

Study Site 012

Lexington, Kentucky, 40536, United States

WITHDRAWN

Study Site 002

Boston, Massachusetts, 02115, United States

RECRUITING

Study Site 006

St Louis, Missouri, 63110, United States

RECRUITING

Study Site 003

Durham, North Carolina, 27710, United States

RECRUITING

Study Site 021

Cleveland, Ohio, 44195, United States

RECRUITING

Study Site 022

Fort Worth, Texas, 76104, United States

RECRUITING

Study Site 005

Morgantown, West Virginia, 26506, United States

RECRUITING

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Asphyxia Neonatorum

Interventions

RLS-0071

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Lori Upham

CONTACT

757-901-0331; Lupham@realtals.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The blinded study team members (eg, Investigators and study staff) and participants' parent(s)/legal guardian(s) will be blinded to treatment group assignments throughout the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two-Stage, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study

Study Record Dates

• First Submitted: March 3, 2023
• First Posted: March 21, 2023
• Study Start: July 27, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)