RLS-0071 for Hypoxic-Ischemic Encephalopathy

(STAR Trial)

Recruiting at 12 trial locations

Overseen By Lori Upham

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: ReAlta Life Sciences, Inc.

Disqualifiers: Congenital abnormalities, Sepsis, Hypotension, others

Stay on Your Current Meds You can continue your current medications while participating

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 17

42 Participants Needed

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. ^{1 2 3 4 5}

How 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. ^{1 2 6 7 8}

Eligibility 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.

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.

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

Treatment Details

Interventions

• Placebo
• RLS-0071

Trial Overview 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.

Participant Groups

Group I: RLS-0071 Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 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

Who Is Running the Clinical Trial?

ReAlta Life Sciences, Inc.

Lead Sponsor

Trials

6

Recruited

220+

Premier Research Group plc

Industry Sponsor

Trials

65

Recruited

74,200+

John Ratliff

Premier Research Group plc

Chief Executive Officer since 2024

MBA

Dr. Milena Kanova-Petrova

Premier Research Group plc

Chief Medical Officer since 2024

MD

Findings from Research

In an animal model of perinatal hypoxic ischemic encephalopathy (HIE), the anti-inflammatory peptide RLS-0071 demonstrated significant neuronal protection and reduced brain damage when used in combination with hypothermia, showing promising results in both acute and long-term outcomes.

RLS-0071 not only decreased levels of the complement protein C1q, indicating a reduction in inflammation, but also improved neurocognitive function in rat pups, suggesting its potential as a therapeutic intervention for HIE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model. Kumar, P., Hair, P., Cunnion, K., et al.[2021]

The rodent model of hypoxic-ischemic encephalopathy, involving 7-day-old pup rats with unilateral carotid artery ligation and timed hypoxia, is a widely used and effective tool for studying brain injury mechanisms and potential therapies.

This model is advantageous due to its low mortality rate, ease of surgical implementation, and suitability for long-term studies, making it essential for preclinical trials in perinatal medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental models of hypoxic-ischemic encephalopathy: hypoxia-ischemia in the immature rat. Carloni, S., Balduini, W.[2016]

Therapeutic hypothermia in infants with hypoxic-ischemic encephalopathy (HIE) was found to significantly increase the risk of thrombocytopenia and cardiac arrhythmia, based on a meta-analysis of 13 trials involving 1806 infants.

While therapeutic hypothermia is used to treat HIE, the increased risks associated with its use highlight the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Moderate Hypothermia for Perinatal Hypoxic-Ischemic Encephalopathy: A Meta-analysis. Zhang, W., Ma, J., Danzeng, Q., et al.[2018]

Neonatal hypoxic-ischemic encephalopathy (HIE) is a significant cause of long-term disability, highlighting the urgent need for research into both repurposing existing drugs and developing new treatments.

A structured preclinical testing approach is essential, starting with in vitro models like hippocampal organotypic slice cultures, followed by rodent and large animal models, to evaluate the efficacy and safety of new pharmacological treatments in conjunction with therapeutic hypothermia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental Models for Testing the Efficacy of Pharmacological Treatments for Neonatal Hypoxic-Ischemic Encephalopathy. Landucci, E., Pellegrini-Giampietro, DE., Facchinetti, F.[2023]

In a study of 167 term infants with moderate to severe hypoxic-ischemic encephalopathy (HIE), treatment with erythropoietin significantly reduced the risk of death or disability at 18 months compared to conventional treatment, with 24.6% of the erythropoietin group experiencing adverse outcomes versus 43.8% in the control group.

Erythropoietin was particularly effective for infants with moderate HIE, showing improved long-term neurodevelopmental outcomes, while no significant benefits were observed for those with severe HIE, and the treatment was found to be safe with no negative side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. Zhu, C., Kang, W., Xu, F., et al.[2011]

Using a P10-11 rat model for hypoxic-ischemic encephalopathy (HIE) provides a more relevant approach for studying therapeutic hypothermia (TH) compared to the previously used P7 model, as it better mimics the brain development of a term infant.

Therapeutic hypothermia showed neuroprotective effects at 2 and 12 weeks post-injury, improving motor function in cases of moderate brain damage, but did not protect against severe damage or improve recognition memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic hypothermia and hypoxia-ischemia in the term-equivalent neonatal rat: characterization of a translational preclinical model. Patel, SD., Pierce, L., Ciardiello, A., et al.[2022]

Therapeutic hypothermia significantly reduces the risk of death or major neurodevelopmental disability in newborns with hypoxic ischemic encephalopathy (HIE), with a risk ratio of 0.76 based on a review of seven trials involving 1214 newborns.

Both total body cooling and selective head cooling methods are effective in improving survival rates and neurological function in these newborns, suggesting that hypothermia should be routinely considered in clinical care for HIE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. Tagin, MA., Woolcott, CG., Vincer, MJ., et al.[2022]

Remote ischemic postconditioning (RIPC) shows potential neuroprotective effects in animal models of hypoxic-ischemic encephalopathy (HIE), but the evidence is inconsistent and lacks clarity due to varied methodologies across studies.

Out of five studies analyzed, RIPC improved certain metabolic markers in piglets, but overall outcomes were mixed, indicating a need for standardized research methods and clinically relevant measures in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote ischemic postconditioning for neuroprotection after newborn hypoxia-ischemia: systematic review of preclinical studies. Andelius, TCK., Henriksen, TB., Kousholt, BS., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Experimental models of hypoxic-ischemic encephalopathy: hypoxia-ischemia in the immature rat. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Safety of Moderate Hypothermia for Perinatal Hypoxic-Ischemic Encephalopathy: A Meta-analysis. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Experimental Models for Testing the Efficacy of Pharmacological Treatments for Neonatal Hypoxic-Ischemic Encephalopathy. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. [2011]

6. United States pubmed.ncbi.nlm.nih.gov

Therapeutic hypothermia and hypoxia-ischemia in the term-equivalent neonatal rat: characterization of a translational preclinical model. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Remote ischemic postconditioning for neuroprotection after newborn hypoxia-ischemia: systematic review of preclinical studies. [2023]