RLS-0071 for Hypoxic-Ischemic Encephalopathy
(STAR Trial)
Recruiting in Palo Alto (17 mi)
+12 other locations
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: ReAlta Life Sciences, Inc.
Disqualifiers: Congenital abnormalities, Sepsis, Hypotension, others
Stay on Your Current Meds
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial protocol does not specify whether participants must stop taking their current medications. It is best to discuss your current medications with the trial team to get a clear answer.
Is RLS-0071 safe for humans?
There is no specific safety data available for RLS-0071 in humans, but it has been tested in animal models for brain injury, showing some protective effects without reported safety concerns.
12345How does the drug RLS-0071 differ from other treatments for hypoxic-ischemic encephalopathy?
RLS-0071 is unique because it targets the complement system, which is part of the immune response, to reduce brain damage in hypoxic-ischemic encephalopathy. It has shown effectiveness in combination with therapeutic hypothermia, a standard treatment, by reducing brain lesion volume and improving neurocognitive outcomes in animal models.
12678Eligibility Criteria
This trial is for newborns with moderate or severe brain injury due to lack of oxygen (HIE) who are undergoing cooling therapy. They must be from a single birth, at least 36 weeks gestation, and have specific signs of encephalopathy before cooling starts. Babies with serious bleeding in the brain, suspected infections, extreme low blood pressure unresponsive to drugs, major congenital issues, or other non-HIE related brain injuries cannot participate.Inclusion Criteria
Product of a singleton pregnancy
≥ 36 weeks gestation
I am eligible for cold temperature treatment.
+4 more
Exclusion Criteria
My unborn baby has been diagnosed with a brain issue or hydrocephalus.
I have a known major genetic or chromosomal abnormality.
I cannot start the study drug within 10 hours of birth.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment Stage 1
Participants receive ascending doses of RLS-0071 or placebo for 72 hours in addition to standard of care treatment, including therapeutic hypothermia.
1 week
Continuous monitoring during treatment
Monitoring and Assessment
Participants are monitored and assessed for safety and exploratory evaluations through Day 14.
2 weeks
Regular assessments until Day 14
Long-term Follow-up
Participants are observed for long-term outcomes until they reach 24 months of age, including neurodevelopmental assessments.
24 months
Periodic assessments at 3, 6, 12, 18, and 24 months
Participant Groups
The study tests RLS-0071's safety and ability to tolerate it as a potential treatment for HIE in newborns compared to a placebo. Newborns will either receive RLS-0071 or an inactive substance while they undergo therapeutic hypothermia—a standard treatment where the baby's body temperature is lowered to help heal the brain.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: RLS-0071Experimental Treatment1 Intervention
Doses of RLS-0071 to be administered every 8 hours (q8h), for a total of 10 doses over 72 hours.
Group II: PlaceboPlacebo Group1 Intervention
Doses of sterile saline (sodium chloride, 0.9%) to be administered every 8 hours (q8h), for a total of 10 doses over 72 hours.
RLS-0071 is already approved in United States for the following indications:
🇺🇸 Approved in United States as RLS-0071 for:
- Hypoxic-ischemic encephalopathy (HIE) in neonates - Fast Track designation, not yet approved
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Study Site 020San Diego, CA
Study Site 019San Diego, CA
Study Site 018Miami, FL
Study Site 010Orlando, FL
More Trial Locations
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Who Is Running the Clinical Trial?
ReAlta Life Sciences, Inc.Lead Sponsor
Premier Research Group plcIndustry Sponsor
References
Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model. [2021]Perinatal hypoxic ischemic encephalopathy (HIE) remains a major contributor of infant death and long-term disability worldwide. The role played by the complement system in this ischemia-reperfusion injury remains poorly understood. In order to better understand the role of complement activation and other modifiable mechanisms of injury in HIE, we tested the dual-targeting anti-inflammatory peptide, RLS-0071 in an animal model of HIE. Using the well-established HIE rat pup model we measured the effects of RLS-0071 during the acute stages of the brain injury and on long-term neurocognitive outcomes. Rat pups subject to hypoxia-ischemia insult received one of 4 interventions including normothermia, hypothermia and RLS-0071 with and without hypothermia. We measured histopathological effects, brain C1q levels and neuroimaging at day 1 and 21 after the injury. A subset of animals was followed into adolescence and evaluated for neurocognitive function. On histological evaluation, RLS-0071 showed neuronal protection in combination with hypothermia (P = 0.048) in addition to reducing C1q levels in the brain at 1hr (P = 0.01) and at 8 hr in combination with hypothermia (P = 0.005). MRI neuroimaging demonstrated that RLS-0071 in combination with hypothermia reduced lesion volume at 24 hours (P
Experimental models of hypoxic-ischemic encephalopathy: hypoxia-ischemia in the immature rat. [2016]The development of experimental models to study the mechanisms of perinatal hypoxic-ischemic encephalopathy and stroke and effective therapies represents an important goal in perinatal medicine. However, due to the complexity of this pathological condition in humans, to date there is no ideal animal model that completely reproduces this condition. This unit describes the most widely used rodent animal model for the study of hypoxic-ischemic encephalopathy during development. The model consists of 7-day-old pup rats subjected to unilateral carotid artery ligation followed by timed hypoxia exposure, and incorporates both focal cerebral ischemia and reperfusion. Its strength lies in the relative ease of the surgical procedure, the low mortality rate, and the possibility of performing long-term experiments, a necessity for preclinical therapeutic trials. Over the years, this model has been extensively characterized, and most information on the mechanisms responsible for neurodegeneration and possible therapeutic approaches following hypoxia-ischemia during brain development derives from studies performed using this model.
Safety of Moderate Hypothermia for Perinatal Hypoxic-Ischemic Encephalopathy: A Meta-analysis. [2018]We investigated the safety of therapeutic hypothermia during intervention in infants with hypoxic-ischemic encephalopathy (HIE).
Experimental Models for Testing the Efficacy of Pharmacological Treatments for Neonatal Hypoxic-Ischemic Encephalopathy. [2023]Representing an important cause of long-term disability, term neonatal hypoxic-ischemic encephalopathy (HIE) urgently needs further research aimed at repurposing existing drug as well as developing new therapeutics. Since various experimental in vitro and in vivo models of HIE have been developed with distinct characteristics, it becomes important to select the appropriate preclinical screening cascade for testing the efficacy of novel pharmacological treatments. As therapeutic hypothermia is already a routine therapy for neonatal encephalopathy, it is essential that hypothermia be administered to the experimental model selected to allow translational testing of novel or repurposed drugs on top of the standard of care. Moreover, a translational approach requires that therapeutic interventions must be initiated after the induction of the insult, and the time window for intervention should be evaluated to translate to real world clinical practice. Hippocampal organotypic slice cultures, in particular, are an invaluable intermediate between simpler cell lines and in vivo models, as they largely maintain structural complexity of the original tissue and can be subjected to transient oxygen-glucose deprivation (OGD) and subsequent reoxygenation to simulate ischemic neuronal injury and reperfusion. Progressing to in vivo models, generally, rodent (mouse and rat) models could offer more flexibility and be more cost-effective for testing the efficacy of pharmacological agents with a dose-response approach. Large animal models, including piglets, sheep, and non-human primates, may be utilized as a third step for more focused and accurate translational studies, including also pharmacokinetic and safety pharmacology assessments. Thus, a preclinical proof of concept of efficacy of an emerging pharmacological treatment should be obtained firstly in vitro, including organotypic models, and, subsequently, in at least two different animal models, also in combination with hypothermia, before initiating clinical trials.
Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. [2011]The purpose of this study was to evaluate the efficacy and safety of erythropoietin in neonatal hypoxic-ischemic encephalopathy (HIE), by using a randomized, prospective study design.
Therapeutic hypothermia and hypoxia-ischemia in the term-equivalent neonatal rat: characterization of a translational preclinical model. [2022]Hypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity in survivors. Therapeutic hypothermia (TH) is the only available intervention, but the protection is incomplete. Preclinical studies of HIE/TH in the rodent have relied on the postnatal day (P) 7 rat whose brain approximates a 32-36 wk gestation infant, less relevant for these studies. We propose that HIE and TH in the term-equivalent P10 rat will be more translational.
Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. [2022]To establish the evidence of therapeutic hypothermia for newborns with hypoxic ischemic encephalopathy(HIE).
Remote ischemic postconditioning for neuroprotection after newborn hypoxia-ischemia: systematic review of preclinical studies. [2023]Hypoxic-ischemic encephalopathy (HIE) is a major contributor to death and disability worldwide. Remote ischemic postconditioning (RIPC) may offer neuroprotection but has only been tested in preclinical models. Various preclinical models with different assessments of outcomes complicate interpretation. The objective of this systematic review was to determine the neuroprotective effect of RIPC in animal models of HIE.