Hypoxic-Ischemic EncephalopathyPhase 2/3STARNCT05778188
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RLS-0071 in Newborns With Moderate or Severe Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia
A Phase 2/3 study testing RLS-0071 in people with Hypoxic-Ischemic Encephalopathy, run by ReAlta Life Sciences, Inc. at 22 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 10 hours
- Conditions the study is for
- Hypoxic-Ischemic Encephalopathy
- What is being tested?
- RLS-0071
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 173 participants
- Where
- 22 sitesUnited States
- Study dates
- 27 Jul 2023to Dec 2028
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 10 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- ≥ 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 to 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 from criterion (a) and one clinical sign of encephalopathy from 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.
- OR
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- appearance, pulse, grimace, activity, and respiration (APGAR) score 2-5 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.
Who cannot join
- 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.
- Participant's head circumference is < 30 cm.
- 10-minute APGAR score < 2, if available.
Show all 14Show fewer
- 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 is being considered.
- Suspected or confirmed fetal alcohol syndrome or suspected substance withdrawal seizures.
- Any other condition that the investigator may consider would make the participant ineligible for the study or place the participant at an unacceptable risk, including a clinically significant (eg, Grade 3 or 4) intracranial hemorrhage.
Trial locations and contacts
22 sites in 1 country. Contact the study team or a site near you to ask about taking part.
22 sites in 1 country
United States22 sites, 21 recruiting
- Recruiting
Study Site 027
Aurora, Colorado, 80045
- Recruiting
Study Site 029
Boston, Massachusetts, 02114
- Recruiting
Study Site 002
Boston, Massachusetts, 02115
- Recruiting
Study Site 021
Cleveland, Ohio, 44195
- Recruiting
Study Site 003
Durham, North Carolina, 27710
- Recruiting
Study Site 022
Fort Worth, Texas, 76104
- Recruiting
Study Site 001
Gainesville, Florida, 32608
- Recruiting
Study Site 030
Houston, Texas, 77030
- Recruiting
Study Site 014
Indianapolis, Indiana, 46202
- Withdrawn
Study Site 012
Lexington, Kentucky, 40536
- Recruiting
Study Site 016
Little Rock, Arkansas, 72202
- Recruiting
Study Site 025
Louisville, Kentucky, 40202
- Recruiting
Study Site 024
Manhasset, New York, 11030-3816
- Recruiting
Study Site 018
Miami, Florida, 33143
- Recruiting
Study Site 005
Morgantown, West Virginia, 26506
- Recruiting
Study Site 023
New Hyde Park, New York, 11040
- Recruiting
Study Site 028
New York, New York, 10032
- Recruiting
Study Site 013
Orange, California, 92868
- Recruiting
Study Site 010
Orlando, Florida, 32803
- Recruiting
Study Site 020
San Diego, California, 92037-7774
- Recruiting
Study Site 019
San Diego, California, 92123
- Recruiting
Study Site 006
St Louis, Missouri, 63110
About this study
Official title: A Phase 2/3, Two-Stage, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RLS-0071 in Newborns With Moderate or Severe Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia With Long-Term Follow-Up
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 efficacy, safety, and tolerability of RLS-0071 in the treatment of newborns with moderate or severe HIE.
Read the detailed description
This is a Phase 2/3, two-stage, multisite, randomized, double-blind, placebo-controlled study to assess the safety, efficacy, and pharmacokinetics (PK) of RLS-0071 in newborns with moderate or severe HIE undergoing therapeutic hypothermia, with long-term follow-up of up to 24 months of age.
The study consists of 2 sequential stages for all participants in all cohorts. In Stage 1, participants will receive either ascending doses of RLS-0071 or a matched volume of placebo every 8 hours (q8h) 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 through Day 14, including magnetic resonance imaging (MRI) measurements of brain injury. After completion of Stage 1, participants will transition to Stage 2 of the study for long-term observation, including developmental assessments, until participants reach 24 months of age.
The Phase 2 portion of the STAR study is designed to inform dose escalation and correlation analysis to affirm that MRI measurement of brain injury in HIE babies is predictive of long-term neurocognitive outcomes at 24 months. The Phase 2 portion of the study consists of Cohort 1 and Cohort 2 subsets. The first recruited cohorts, 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. 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+.
The Phase 3 portion of the study is designed to generate data focusing on assessing the efficacy of RLS-0071 compared to placebo in reducing HIE brain injury as measured by MRI and improving the long-term neurocognitive outcomes at 24 months. The Phase 3 portion of the study consists of Cohort 2+ (2a+ [moderate] or 2b+ [severe]) and Cohort 3 (3a [moderate] or 3b [severe]), with participants recruited in these cohorts receiving 10 mg/kg RLS-0071 or a matched volume of placebo.
- Conditions
- Hypoxic-Ischemic Encephalopathy
- Being tested
- RLS-0071, Placebo
- Keywords
- Birth Asphyxia, Anoxic brain injury
- Medical subject headings
- Hypoxia-Ischemia, Brain, Asphyxia Neonatorum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RLS-0071Drug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| RLS-0071 | Experimental | Doses of RLS-0071 to be administered every 8 hours (q8h), for a total of 10 doses over 72 hours. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Extent of acute brain injury at Day 4 (+3), assessed through magnetic resonance imaging (MRI), using a standardized scoring system
Brain injury is assessed using the Weeke score (Weeke 2018), which 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.
Measured: Day 4 (up to Day 7)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2023
- Study start27 Jul 2023
- Primary completionDec 2026 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hypoxic-Ischemic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two-Stage, Randomized, Double-Blind, Placebo-Controlled Study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 173 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ReAlta Life Sciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Premier Research
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05778188
- Sponsor's protocol ID
- RLS-0071-202
- Acronym
- STAR
- Status last verified
- Nov 2026
- First submitted
- 3 Mar 2023
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Weeke LC, Groenendaal F, Mudigonda K, Blennow M, Lequin MH, Meiners LC, van Haastert IC, Benders MJ, Hallberg B, de Vries LS. A Novel Magnetic Resonance Imaging Score Predicts Neurodevelopmental Outcome After Perinatal Asphyxia and Therapeutic Hypothermia. J Pediatr. 2018 Jan;192:33-40.e2. doi: 10.1016/j.jpeds.2017.09.043.
PubMed 29246356
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2/3, Two-Stage, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RLS-0071 in Newborns With Moderate or Severe Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia With Long-Term Follow-Up
- ClinicalTrials.gov ID
- NCT05778188
- Acronym / sponsor ID
- STAR / RLS-0071-202
- Conditions
- Hypoxic-Ischemic Encephalopathy
- Keywords
- Birth Asphyxia, Anoxic brain injury
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 173 participants (estimated)
- Lead sponsor
- ReAlta Life Sciences, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Premier Research
- Study start
- 27 Jul 2023 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 21 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 efficacy, safety, and tolerability of RLS-0071 in the treatment of newborns with moderate or severe HIE.
Detailed description
This is a Phase 2/3, two-stage, multisite, randomized, double-blind, placebo-controlled study to assess the safety, efficacy, and pharmacokinetics (PK) of RLS-0071 in newborns with moderate or severe HIE undergoing therapeutic hypothermia, with long-term follow-up of up to 24 months of age.
The study consists of 2 sequential stages for all participants in all cohorts. In Stage 1, participants will receive either ascending doses of RLS-0071 or a matched volume of placebo every 8 hours (q8h) 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 through Day 14, including magnetic resonance imaging (MRI) measurements of brain injury. After completion of Stage 1, participants will transition to Stage 2 of the study for long-term observation, including developmental assessments, until participants reach 24 months of age.
The Phase 2 portion of the STAR study is designed to inform dose escalation and correlation analysis to affirm that MRI measurement of brain injury in HIE babies is predictive of long-term neurocognitive outcomes at 24 months. The Phase 2 portion of the study consists of Cohort 1 and Cohort 2 subsets. The first recruited cohorts, 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. 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+.
The Phase 3 portion of the study is designed to generate data focusing on assessing the efficacy of RLS-0071 compared to placebo in reducing HIE brain injury as measured by MRI and improving the long-term neurocognitive outcomes at 24 months. The Phase 3 portion of the study consists of Cohort 2+ (2a+ [moderate] or 2b+ [severe]) and Cohort 3 (3a [moderate] or 3b [severe]), with participants recruited in these cohorts receiving 10 mg/kg RLS-0071 or a matched volume of placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Two-Stage, Randomized, Double-Blind, Placebo-Controlled Study
| Arm | Type | Receives |
|---|---|---|
| RLS-0071 | Experimental | Drug: RLS-0071Doses of RLS-0071 to be administered every 8 hours (q8h), for a total of 10 doses over 72 hours. |
| Placebo | Placebo comparator | Drug: PlaceboDoses of sterile saline (sodium chloride, 0.9%) to be administered every 8 hours (q8h), for a total of 10 doses over 72 hours. |
Who may qualify
- Ages
- Up to 10 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (15 listed)
- ≥ 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 to 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 from criterion (a) and one clinical sign of encephalopathy from criterion (b):
- OR
- Be eligible to receive therapeutic hypothermia.
Key exclusion criteria (14 listed)
- 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.
- Participant's head circumference is < 30 cm.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RLS-0071RLS-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. | Drug | RLS-0071 |
| PlaceboPlacebo 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. | Drug | Placebo |
Primary outcome
Extent of acute brain injury at Day 4 (+3), assessed through magnetic resonance imaging (MRI), using a standardized scoring system
Time frame: Day 4 (up to Day 7)
Brain injury is assessed using the Weeke score (Weeke 2018), which 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Background: PubMed 29246356Weeke LC, Groenendaal F, Mudigonda K, Blennow M, Lequin MH, Meiners LC, van Haastert IC, Benders MJ, Hallberg B, de Vries LS. A Novel Magnetic Resonance Imaging Score Predicts Neurodevelopmental Outcome After Perinatal Asphyxia and Therapeutic Hypothermia. J Pediatr. 2018 Jan;192:33-40.e2. doi: 10.1016/j.jpeds.2017.09.043.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing RLS-0071 in people with Hypoxic-Ischemic Encephalopathy, run by ReAlta Life Sciences, Inc. at 22 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lori Upham (757-901-0331, Lupham@realtals.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Extent of acute brain injury at Day 4 (+3), assessed through magnetic resonance imaging (MRI), using a standardized scoring system (time frame: Day 4 (up to Day 7)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05778188, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.