A Study to Evaluate the Safety and Pharmacokinetics of RC001 in Children With Dravet Syndrome
2026年6月23日 更新者:Second Affiliated Hospital of Guangzhou Medical University
An Investigator-Initiated Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RC001 in Patients With Dravet Syndrome Aged 2 to 18 Years
This is an open-label, single-center study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of intrathecal RC001 in patients with Dravet syndrome aged 2 to 18 years.
The study includes a dose-escalation part followed by a fixed dose treatment part, with participant progression based on investigator-assessed safety and efficacy.
研究概览
地位
招聘中
详细说明
This is an open-label, single-center clinical study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of RC001 administered intrathecally in patients aged 2 to 18 years with Dravet syndrome.
The study consists of two stages: Stage 1 (intra-subject dose escalation) and Stage 2 (fixed-dose multiple dosing).
In Stage 1, three cohorts will be enrolled with a total of three participants.
In Stage 2, a total of five participants will be enrolled to receive fixed-dose multiple administrations.
Participants in both the dose-escalation stage and the fixed-dose multiple dosing stage may enter an extension phase after completion of the last dose, based on the investigator's assessment of efficacy and safety.
研究类型
介入性
注册 (估计的)
8
阶段
- 第一阶段早期
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习联系方式
- 姓名:Weiping Liao, Ph.D
- 电话号码:086-020-34152498
- 邮箱:wpliao@163.net
学习地点
-
-
Guangdong
-
Guangzhou、Guangdong、中国、510120
- 招聘中
- The second Affiliated Hospital of Guangzhou Medical University
-
接触:
- Juan Chen
- 电话号码:086-020-34153599
- 邮箱:gyeylcyjzx@163.com
-
-
参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 孩子
- 成人
接受健康志愿者
不
描述
Inclusion Criteria:
- Patients aged 2-18 years with Dravet syndrome caused by SCN1A mutations, with onset before 12 months of age characterized by focal seizures, hemiclonic seizures, generalized tonic-clonic seizures, or myoclonic seizures, and with MRI excluding progressive neurological disease either historically or at screening. Enrolled participants will be assigned as follows: 1 participant aged 13-18 years, 1 aged 7-12 years, and 1 aged 2-6 years will undergo intra-subject dose escalation; 5 participants aged 2-12 years will receive fixed-dose multiple administrations.
- Seizure frequency requirements: at least 6 cumulative seizures within 12 weeks prior to the day of signing the ICF, and at least 2 seizures within 4 weeks prior to ICF signing. For participants in Stage 2 (fixed-dose multiple administration), seizure frequency must also be ≥4 within 4 weeks after ICF signing.
- Documented pathogenic or likely pathogenic variants in the SCN1A gene associated with Dravet syndrome.
- Prior treatment with at least one anti-epileptic intervention, including anti-seizure medications (ASM), ketogenic diet, or vagus nerve stimulation (VNS), with inadequate seizure control or discontinuation due to adverse events (AEs).
- Use of at least one ASM prior to screening, with a stable dose for at least 4 weeks before screening.
- All epilepsy-related treatments, including ASM and other interventions (ketogenic diet and VNS), must be stable for at least 4 weeks prior to screening and are expected to remain stable throughout the study (medications adjusted by body weight are allowed).
- Willingness to participate and provision of written informed consent.
Exclusion Criteria:
- Presence of other known pathogenic gene mutations causing Dravet syndrome, or SCN1A gain-of-function mutations reported in the literature and/or experimentally validated, including but not limited to: Ala23Glu, Thr162Ile, Thr226Met, Ser228Pro, Val229Leu, Ile236Val, Ile236Thr, Val250Leu, Leu263Val, Thr398Met, Ala420Val, Val422Leu, Ile883Thr, Leu893Phe, Ala989Thr, Thr1174Ser, Trp1204Arg, Ala1339Asp, Pro1345Ser, Pro1345Leu, Ser1346Pro, Ile1347Val, Val1481Ile, Ile1483Met, Gln1489Lys, Ile1498Thr, Ile1498Met, Phe1499Leu, Met1500Val, Arg1575Cys, Val1611Phe, Leu1624Pro, Arg1636Gln, Arg1648Cys, Leu1649Gln, Leu1660Ile, Phe1661Leu, Ala1669Glu, Leu1670Trp, Gly1674Arg, Phe1774Ser, Asp1866Tyr.
- Current maintenance treatment with anti-epileptic drugs primarily acting as sodium channel blockers, including but not limited to carbamazepine, oxcarbazepine, lamotrigine, lacosamide, or rufinamide.
- Ongoing neuromodulation therapy (e.g., responsive neurostimulation or deep brain stimulation), excluding vagus nerve stimulation (VNS).
- Receipt of gene therapy or cell therapy within 1 year prior to screening.
- Receipt of any vaccination within 12 weeks prior to screening.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2× the upper limit of normal (ULN), or total bilirubin >1.5× ULN; renal insufficiency or serum creatinine >1.2× ULN.
- Presence of any severe uncontrolled disease other than Dravet syndrome.
- History of autoimmune disease, or uncontrolled infectious disease within 1 week prior to screening.
- History of brain or spinal cord disease (other than epilepsy, Dravet syndrome, or trauma), or history of bacterial meningitis.
- Spinal deformity or other conditions that may interfere with normal cerebrospinal fluid (CSF) flow, or implantation of a CSF shunt.
- Pregnant or breastfeeding females.
- Any other significant disease or condition that, in the investigator's judgment, may pose a risk to the patient, interfere with study results, or affect the patient's ability to participate in the study.
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的:Dose Escalation Cohort
Participants will receive RC001 in a dose-escalation manner to evaluate the safety, tolerability, and preliminary pharmacodynamic effects.
Dose levels will be administered sequentially, and escalation decisions will be based on safety data from previously treated participants.
This cohort includes 3 participants.
|
RC001 will be administered using a sequential dose-escalation scheme.
Participants will receive ascending dose levels of RC001 according to the study protocol.
Dose escalation will proceed only after safety data from prior participants have been reviewed and deemed acceptable.
This intervention is intended to evaluate safety, tolerability, and preliminary pharmacodynamic effects at increasing dose levels.
|
|
实验性的:Fixed Dose Cohort
Participants will receive a predefined fixed dose of RC001 selected based on safety, tolerability, and pharmacological data obtained from the dose-escalation cohort.
This cohort is designed to further evaluate safety and preliminary efficacy at the selected dose level.
This cohort includes 5 participants.
|
RC001 will be administered at a predefined fixed dose level selected based on safety, tolerability, and pharmacological data obtained from the dose-escalation cohort.
This intervention is intended to further evaluate safety and preliminary efficacy at the selected dose level in a fixed-dose setting.
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
大体时间:From first dose to 24 weeks after the last dose
|
A treatment-emergent adverse event is defined as any adverse event that occurs or worsens after the first dose of RC001 through the end of follow-up.
TEAEs will be summarized by system organ class, preferred term, severity, seriousness, and relationship to study drug or study procedure.
|
From first dose to 24 weeks after the last dose
|
|
Number of Participants With Serious Adverse Events (SAEs)
大体时间:From signing informed consent to 24 weeks after the last dose
|
Serious adverse events will be collected and summarized throughout the study.
|
From signing informed consent to 24 weeks after the last dose
|
|
Number of Participants With Clinically Significant Abnormalities in Vital Signs
大体时间:From baseline to 24 weeks after the last dose
|
Vital signs include body temperature, heart rate, respiratory rate, systolic blood pressure, and diastolic blood pressure.
Clinically significant abnormalities will be determined by the investigator.
|
From baseline to 24 weeks after the last dose
|
|
Number of Participants With Clinically Significant Abnormal Physical Examination Findings
大体时间:From baseline to 24 weeks after the last dose
|
Physical examination findings will be assessed for clinically significant abnormalities as determined by the investigator.
|
From baseline to 24 weeks after the last dose
|
|
Number of Participants With Clinically Significant Abnormal Laboratory Test Results
大体时间:From baseline to 24 weeks after the last dose
|
Laboratory assessments may include hematology, serum chemistry, coagulation, urinalysis, and cerebrospinal fluid laboratory tests, as applicable.
Clinically significant abnormalities will be determined by the investigator.
|
From baseline to 24 weeks after the last dose
|
|
Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings
大体时间:From baseline to 24 weeks after the last dose
|
ECG parameters may include heart rate, PR interval, QRS duration, QT interval, and corrected QT interval.
Clinically significant abnormalities will be determined by the investigator.
|
From baseline to 24 weeks after the last dose
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of RC001
大体时间:From first dose to last dose up to 12 weeks
|
Cmax of RC001 in plasma following intrathecal administration.
|
From first dose to last dose up to 12 weeks
|
|
Time to Maximum Observed Plasma Concentration (Tmax) of RC001
大体时间:From first dose through 12 weeks
|
Tmax of RC001 in plasma following intrathecal administration.
|
From first dose through 12 weeks
|
|
Trough Concentration (Ctrough) of RC001 in Cerebrospinal Fluid
大体时间:Prior to each dose through 12 weeks
|
Trough concentration of RC001 in cerebrospinal fluid before each intrathecal dose.
|
Prior to each dose through 12 weeks
|
|
Percentage Change From Baseline in Countable Seizure Frequency at 12 Weeks After the Last Dose
大体时间:Baseline and the 28-day period preceding 12 weeks after the last dose
|
Countable seizure frequency will be calculated as the number of countable seizures during the 28-day period preceding 12 weeks after the last dose of RC001.Baseline countable seizure frequency is defined as the number of countable seizures during baseline observation period.
Percentage change from baseline will be calculated as: (post-baseline 28-day seizure frequency - baseline 28-day seizure frequency) / baseline 28-day seizure frequency x 100%.
|
Baseline and the 28-day period preceding 12 weeks after the last dose
|
|
Percentage Change From Baseline in Countable Seizure Frequency at 24 Weeks After the Last Dose
大体时间:Baseline and the 28-day period preceding 24 weeks after the last dose
|
Countable seizure frequency will be calculated as the number of countable seizures during the 28-day period preceding 24 weeks after the last dose of RC001.
Baseline countable seizure frequency is defined as the number of countable seizures during baseline observation period.
Percentage change from baseline will be calculated as: (post-baseline 28-day seizure frequency - baseline 28-day seizure frequency) / baseline 28-day seizure frequency x 100%.
|
Baseline and the 28-day period preceding 24 weeks after the last dose
|
|
Clinical Global Impression of Change (CGI-C) Score at 24 Weeks After the Last Dose
大体时间:24 weeks after the last dose
|
The Clinical Global Impression of Change (CGI-C) is a clinician-rated 7-point scale assessing overall clinical change relative to baseline.
Scores range from 1 to 7: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
Lower scores indicate greater improvement.
|
24 weeks after the last dose
|
|
Caregiver Global Impression of Change (CaGI-C) Score at 24 Weeks After the Last Dose
大体时间:24 weeks after the last dose
|
The Caregiver Global Impression of Change (CaGI-C) is a caregiver-rated 7-point scale assessing overall clinical change relative to baseline.
Scores range from 1 to 7: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
Lower scores indicate greater improvement.
|
24 weeks after the last dose
|
|
Change From Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Expressive Communication Raw Score at 24 Weeks After the Last Dose
大体时间:Baseline and 24 weeks after the last dose
|
The Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) measures adaptive behavior.
The Expressive Communication subdomain raw score will be assessed.
Raw scores have a minimum value of 0, and the maximum value varies by subdomain according to the Vineland-3 scoring manual.
Higher scores indicate better adaptive functioning.
|
Baseline and 24 weeks after the last dose
|
|
Change From Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Receptive Communication Raw Score at 24 Weeks After the Last Dose
大体时间:Baseline and 24 weeks after the last dose
|
The Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) measures adaptive behavior.
The Receptive Communication subdomain raw score will be assessed.
Raw scores have a minimum value of 0, and the maximum value varies by subdomain according to the Vineland-3 scoring manual.
Higher scores indicate better adaptive functioning.
|
Baseline and 24 weeks after the last dose
|
|
Change From Baseline in Age-Appropriate Wechsler Intelligence Scale Score at 24 Weeks After the Last Dose
大体时间:Baseline and 24 weeks after the last dose
|
Cognitive function will be assessed using an age-appropriate Wechsler intelligence scale.
The selected composite or total score will be analyzed as the change from baseline.
Higher scores indicate better cognitive functioning.
The applicable scale version and score range will be defined according to the participant's age and the study assessment manual.
|
Baseline and 24 weeks after the last dose
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2025年12月22日
初级完成 (估计的)
2027年12月31日
研究完成 (估计的)
2027年12月31日
研究注册日期
首次提交
2026年6月16日
首先提交符合 QC 标准的
2026年6月23日
首次发布 (实际的)
2026年6月30日
研究记录更新
最后更新发布 (实际的)
2026年6月30日
上次提交的符合 QC 标准的更新
2026年6月23日
最后验证
2025年12月1日
更多信息
与本研究相关的术语
其他研究编号
- 2025-LCYJ-187
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
不
IPD 计划说明
Individual participant data (IPD) from this early-phase study will not be shared due to the sensitive nature of patient data and the need to protect participant privacy.
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.