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.
≥ 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.
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
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.
Parallel
RLS-0071
DrugRLS-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.
Placebo
DrugPlacebo 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.
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).
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.
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
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.
Composite of mortality and neurodevelopmental impairment (NDI) at 24 months
Mortality at 3, 6, 12, 18, and 24 months
Number of participants alive at each timepoint
Number of participants with clinically significant laboratory abnormalities, events of special interest, and SAEs at 3, 6, 12, and 18 months
Neurocognitive developmental outcome assessed by Bayley-4 at 24 months of age
The Bayley Scales of Infant and Toddler Development (4th Edition) consists of 5 subdomains: the Cognitive, Language, Motor, Social-Emotional, and Adaptive Behavior scales. Cognitive, Language, and Motor domains include a total of 264 items, each ranked between 0-2 (where 0 is not present and 2 is mastery); the Social-Emotional and Adaptive Behavior domains are assessed through caregiver questionnaires.
PK parameters of RLS-0071 at multiple-ascending doses: Cmax
Maximum serum concentration observed (Cmax) of RLS-0071
PK parameters of RLS-0071 at multiple-ascending doses: Ctrough
Concentration observed prior to subsequent or final dosing (Ctrough) of RLS-0071
PK parameters of RLS-0071 at multiple-ascending doses: Area under the curve
Area under the curve (AUC) of RLS-0071 concentration in serum
Number of participants diagnosed with epilepsy during the first 2 years of life
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ReAlta Life Sciences, Inc.
Lead sponsor
Premier Research
Collaborator
