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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Lori Upham
- 電話番号：757-901-0331
- メール：Lupham@realtals.com
研究場所
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Arkansas
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Little Rock、Arkansas、アメリカ、72202
- 募集
- Study Site 016
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California
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Orange、California、アメリカ、92868
- 募集
- Study Site 013
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San Diego、California、アメリカ、92123
- 募集
- Study Site 019
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San Diego、California、アメリカ、92037-7774
- 募集
- Study Site 020
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Colorado
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Aurora、Colorado、アメリカ、80045
- 募集
- Study Site 027
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Florida
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Gainesville、Florida、アメリカ、32608
- 募集
- Study Site 001
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Miami、Florida、アメリカ、33143
- 募集
- Study Site 018
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Orlando、Florida、アメリカ、32803
- 募集
- Study Site 010
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Indiana
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Indianapolis、Indiana、アメリカ、46202
- 募集
- Study Site 014
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Kentucky
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Lexington、Kentucky、アメリカ、40536
- 引きこもった
- Study Site 012
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Louisville、Kentucky、アメリカ、40202
- 募集
- Study Site 025
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Massachusetts
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Boston、Massachusetts、アメリカ、02115
- 募集
- Study Site 002
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Boston、Massachusetts、アメリカ、02114
- 募集
- Study Site 029
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Missouri
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St Louis、Missouri、アメリカ、63110
- 募集
- Study Site 006
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New York
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Manhasset、New York、アメリカ、11030-3816
- 募集
- Study Site 024
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New Hyde Park、New York、アメリカ、11040
- 募集
- Study Site 023
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New York、New York、アメリカ、10032
- 募集
- Study Site 028
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North Carolina
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Durham、North Carolina、アメリカ、27710
- 募集
- Study Site 003
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Ohio
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Cleveland、Ohio、アメリカ、44195
- 募集
- Study Site 021
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Texas
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Fort Worth、Texas、アメリカ、76104
- 募集
- Study Site 022
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Houston、Texas、アメリカ、77030
- 募集
- Study Site 030
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West Virginia
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Morgantown、West Virginia、アメリカ、26506
- 募集
- Study Site 005
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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. |
|
プラセボコンパレーター：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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Extent of acute brain injury at Day 4 (+3), assessed through magnetic resonance imaging (MRI), using a standardized scoring system
時間枠：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)
|
協力者と研究者
協力者
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- RLS-0071-202
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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