2024-515598-82-00招募中3 期
A Randomized, Multi-Center, Double-Blind, Sham-Procedure-Controlled Clinical Trial to Investigate the Efficacy and Safety of Elsunersen in Pediatric Participants with Early Onset SCN2A Developmental and Epileptic Encephalopathy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Median percent change in monthly (28 days) motor seizure frequency from baseline to treatment after 24 weeks
研究概览
简要总结
To assess the efficacy of elsunersen on seizure frequency in participants with early-onset SCN2A-DEE
研究设计
- 分配方式
- Non-randomized
- 主要目的
- Extension Period: Cohort 3
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 64 years（0-17 Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Participant, or parent/legal guardian, is willing to sign an informed consent document indicating that he/she understands the purpose of the clinical trial; understands, and can perform, complete, and comply with all the procedures and assessments that are required during the clinical trial; and is willing to participate in the clinical trial.
- •Has an eGFR ≥ 60 mL/min/1.73 m², calculated using the Schwartz formula (updated bedside version).
- •Has a documented Gain of Function SCN2A variant confirmed through genetic testing.
- •Has onset of seizures prior to 3 months of age.
- •Is between the ages of 0 (with a gestational age of at least 37 weeks +1 day) to ≤18 years at Screening.
- •Seizure frequency of 4 or more countable motor seizures refractory to current treatment per 28-day during the Baseline Observation Period.
- •If prescribed any ASM or non-pharmacological intervention (including ketogenic diet and vagus nerve stimulation [VNS]) for the treatment of epilepsy or other symptoms of early-onset SCN2A-DEE (auxiliary medicinal products) is on a stable dose, settings, or parameters for 1 month prior to Screening (not to include weight-based dose changes of medications).
- •Has been reviewed by the Eligibility Review Committee (ERC) prior to randomization, including documentation of variant characterization, disease etiology, magnetic resonance imaging (MRI) results, and seizure frequency.
- •Seizure diary completion must occur on ≥80% days in the Screening/Observation
- •Has a serum total bilirubin value <1.5× the upper limit of normal (ULN) or a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value <3×ULN.
排除标准
- •At screening, has any significant ongoing disease, disorder, laboratory abnormalities, environmental factor, or any ongoing or history of any psychiatric, medical, or surgical condition that, in the judgment of the investigator in consultation with the medical monitor and/or sponsor’s designee, might jeopardize the participant’s safety or interfere with the absorption, distribution, metabolism, or excretion of elsunersen; impact the clinical trial scientific objectives, or interfere with participation in the clinical trial.
- •Is currently pregnant or breastfeeding or is planning to become pregnant during the clinical trial or within the timeframe specified in Section 5.5.3 of the protocol.
- •Has any abnormal findings on brain MRI that may be contributing to the participant’s epilepsy, would put the participant at increased risk of ASO therapy (including but not limited to hydrocephalus), or any other finding that may be considered clinically significant as judged by the PI or ERC. Note: If a brain MRI has not been performed within 6 months of screening, the participant will need to have a brain MRI without gadolinium as part of Screening to assess ventricle size.
- •Has any clinically significant or known pathogenic genetic variant other than in the SCN2A gene, or a genetic variant that may explain or contribute to the participant’s epilepsy and/or developmental disorder, in the opinion of the investigator or confirmed by the ERC.
- •Has any other/additional etiology for epilepsy and/or DEE (e.g. encephalomalacia, etc) in the opinion of the investigator or confirmed by the ERC.
- •Has bone, spine (eg, kyphosis, scoliosis), bleeding, or other disorder (including, but not limited to, intolerance to anesthesia, if applicable) that might expose the participant to risk of injury or unsuccessful lumbar puncture.
- •Is unwilling or unable to discontinue medications that might increase the risk of bleeding (eg, heparin, low molecular weight heparin, platelet inhibitors) during the clinical trial (as defined in Section 6.6.1 of the protocol).
- •Is required to take any excluded medication or is anticipated to require treatment with at least 1 excluded medication during the clinical trial (as defined in the relevant section of the protocol).
- •Has laboratory test results at Screening outside the normal ranges for platelet count, prothrombin time (PT)/ partial thromboplastin time (PTT)/ international normalized ratio (INR), or renal function (serum creatinine [sCr] and urine protein [Uprot]), that are clinically meaningful as judged by the investigator.
- •Has received any experimental or investigational drug, device, or other therapy within 30 days or 5 half-lives (whichever is longer) prior to Screening, including any prior use of gene therapy. Note: This restriction does not apply to participants from PRAX-222-111 clinical trial or to patients currently enrolled in Emergency Access for elsunersen, who may enroll directly into the Extension Period.
- •Has a known hypersensitivity to any component of the formulation of elsunersen.
结局指标
主要结局
Median percent change in monthly (28 days) motor seizure frequency from baseline to treatment after 24 weeks
Median percent change in monthly (28 days) motor seizure frequency from baseline to treatment after 24 weeks
次要结局
- Responder rate - defined as a ≥50% reduction in monthly seizure frequency from baseline compared to treatment after 24 weeks
- Change in motor seizure-free days from baseline (Treatment and Extension Periods)
- Clinical Global Impression-Severity (CGI-S) at baseline compared to treatment after 24 weeks (Treatment and Extension Periods)
- Clinical Global Impression-Improvement (CGI-I) subdomains scores at each postdose time point (Treatment and Extension Periods)
- Caregiver Global Impression-Severity (CgGI-S) at baseline compared to treatment after 24 weeks (Treatment and Extension Periods)
- Caregiver Global Impression-Improvement (CgGI-I) subdomains scores at each postdose time point (Treatment and Extension Periods)
- Sleep assessment scores at baseline compared to each postdose time point (Treatment and Extension Periods)
- Incidence and severity of treatment-emergent adverse events (TEAEs) (Treatment and Extension Periods)
- Changes in findings on physical and neurological examinations, vital sign measurements, clinical laboratory results and electrocardiogram (ECG) parameters (Treatment and Extension Periods)
- Plasma and cerebrospinal fluid (CSF) concentrations of elsunersen
- Plasma elsunersen PK parameters
- Changes in the ASM regimen, dose and number of ASMs compared to Baseline (Extension Period Only)
研究者
Scientific/public contact point
Scientific
Praxis Precision Medicines Inc.
研究点 (2)
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