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 (STAR)
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.
Tutkimuksen yleiskatsaus
Tila
Interventio / Hoito
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Vaihe 2
- Vaihe 3
Yhteystiedot ja paikat
Opiskeluyhteys
- Nimi: Lori Upham
- Puhelinnumero: 757-901-0331
- Sähköposti: Lupham@realtals.com
Opiskelupaikat
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Arkansas
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Little Rock, Arkansas, Yhdysvallat, 72202
- Rekrytointi
- Study Site 016
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California
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Orange, California, Yhdysvallat, 92868
- Rekrytointi
- Study Site 013
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San Diego, California, Yhdysvallat, 92123
- Rekrytointi
- Study Site 019
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San Diego, California, Yhdysvallat, 92037-7774
- Rekrytointi
- Study Site 020
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Colorado
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Aurora, Colorado, Yhdysvallat, 80045
- Rekrytointi
- Study Site 027
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Florida
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Gainesville, Florida, Yhdysvallat, 32608
- Rekrytointi
- Study Site 001
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Miami, Florida, Yhdysvallat, 33143
- Rekrytointi
- Study Site 018
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Orlando, Florida, Yhdysvallat, 32803
- Rekrytointi
- Study Site 010
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Indiana
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Indianapolis, Indiana, Yhdysvallat, 46202
- Rekrytointi
- Study Site 014
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Kentucky
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Lexington, Kentucky, Yhdysvallat, 40536
- Peruutettu
- Study Site 012
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Louisville, Kentucky, Yhdysvallat, 40202
- Rekrytointi
- Study Site 025
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Massachusetts
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Boston, Massachusetts, Yhdysvallat, 02115
- Rekrytointi
- Study Site 002
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Boston, Massachusetts, Yhdysvallat, 02114
- Rekrytointi
- Study Site 029
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Missouri
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St Louis, Missouri, Yhdysvallat, 63110
- Rekrytointi
- Study Site 006
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New York
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Manhasset, New York, Yhdysvallat, 11030-3816
- Rekrytointi
- Study Site 024
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New Hyde Park, New York, Yhdysvallat, 11040
- Rekrytointi
- Study Site 023
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New York, New York, Yhdysvallat, 10032
- Rekrytointi
- Study Site 028
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North Carolina
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Durham, North Carolina, Yhdysvallat, 27710
- Rekrytointi
- Study Site 003
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Ohio
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Cleveland, Ohio, Yhdysvallat, 44195
- Rekrytointi
- Study Site 021
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Texas
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Fort Worth, Texas, Yhdysvallat, 76104
- Rekrytointi
- Study Site 022
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Houston, Texas, Yhdysvallat, 77030
- Rekrytointi
- Study Site 030
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West Virginia
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Morgantown, West Virginia, Yhdysvallat, 26506
- Rekrytointi
- Study Site 005
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
Inclusion Criteria:
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≥ 36 weeks gestation.
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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.
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Moderate or severe encephalopathy based on at least one risk of encephalopathy from criterion (a) and one clinical sign of encephalopathy from criterion (b):
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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
- 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]).
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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).
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Be eligible to receive therapeutic hypothermia.
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Active whole-body cooling to be started prior to 6 hours of age (passive cooling is permitted prior to active whole-body cooling).
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Product of a singleton pregnancy.
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Written informed consent obtained from parent or legal guardian.
Exclusion Criteria:
- 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.
- 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.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Nelinkertaistaa
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: RLS-0071
Doses of RLS-0071 to be administered every 8 hours (q8h), for a total of 10 doses over 72 hours. |
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. |
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Placebo Comparator: Placebo
Doses of sterile saline (sodium chloride, 0.9%) to be administered every 8 hours (q8h), for a total of 10 doses over 72 hours. |
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. |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Extent of acute brain injury at Day 4 (+3), assessed through magnetic resonance imaging (MRI), using a standardized scoring system
Aikaikkuna: Day 4 (up to Day 7)
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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. |
Day 4 (up to Day 7)
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Yhteistyökumppanit ja tutkijat
Sponsori
Yhteistyökumppanit
Julkaisuja ja hyödyllisiä linkkejä
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Aivoverenkiertohäiriöt
- Aivojen sairaudet
- Keskushermoston sairaudet
- Hermoston sairaudet
- Verisuonisairaudet
- Sydän-ja verisuonitaudit
- Vauva, vastasyntynyt, sairaudet
- Aivojen iskemia
- Merkit ja oireet, Hengityselimet
- Hypoksia, aivot
- Hypoksia
- Synnynnäiset, perinnölliset ja vastasyntyneiden sairaudet ja poikkeavuudet
- Patologiset tilat, merkit ja oireet
- Merkit ja oireet
- Hypoksia-iskemia, aivot
- Neonatorum asfyksia
- RLS-0071
Muut tutkimustunnusnumerot
- RLS-0071-202
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
Lääke- ja laitetiedot, tutkimusasiakirjat
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