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.
調査の概要
状態
募集
条件
詳細な説明
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.
研究の種類
介入
入学 (推定)
8
段階
- 初期フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前:Weiping Liao, Ph.D
- 電話番号:086-020-34152498
- メール:wpliao@163.net
研究場所
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Guangdong
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Guangzhou、Guangdong、中国、510120
- 募集
- The second Affiliated Hospital of Guangzhou Medical University
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コンタクト:
- Juan Chen
- 電話番号:086-020-34153599
- メール:gyeylcyjzx@163.com
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-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 子
- 大人
健康ボランティアの受け入れ
いいえ
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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:非ランダム化
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的: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.
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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.
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実験的: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.
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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.
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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 |
|---|---|---|
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
時間枠:From first dose to 24 weeks after the last dose
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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.
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From first dose to 24 weeks after the last dose
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Number of Participants With Serious Adverse Events (SAEs)
時間枠:From signing informed consent to 24 weeks after the last dose
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Serious adverse events will be collected and summarized throughout the study.
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From signing informed consent to 24 weeks after the last dose
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Number of Participants With Clinically Significant Abnormalities in Vital Signs
時間枠:From baseline to 24 weeks after the last dose
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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.
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From baseline to 24 weeks after the last dose
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Number of Participants With Clinically Significant Abnormal Physical Examination Findings
時間枠:From baseline to 24 weeks after the last dose
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Physical examination findings will be assessed for clinically significant abnormalities as determined by the investigator.
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From baseline to 24 weeks after the last dose
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Number of Participants With Clinically Significant Abnormal Laboratory Test Results
時間枠:From baseline to 24 weeks after the last dose
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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.
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From baseline to 24 weeks after the last dose
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Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings
時間枠:From baseline to 24 weeks after the last dose
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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.
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From baseline to 24 weeks after the last dose
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Maximum Observed Plasma Concentration (Cmax) of RC001
時間枠:From first dose to last dose up to 12 weeks
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Cmax of RC001 in plasma following intrathecal administration.
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From first dose to last dose up to 12 weeks
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Time to Maximum Observed Plasma Concentration (Tmax) of RC001
時間枠:From first dose through 12 weeks
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Tmax of RC001 in plasma following intrathecal administration.
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From first dose through 12 weeks
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Trough Concentration (Ctrough) of RC001 in Cerebrospinal Fluid
時間枠:Prior to each dose through 12 weeks
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Trough concentration of RC001 in cerebrospinal fluid before each intrathecal dose.
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Prior to each dose through 12 weeks
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Percentage Change From Baseline in Countable Seizure Frequency at 12 Weeks After the Last Dose
時間枠:Baseline and the 28-day period preceding 12 weeks after the last dose
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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%.
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Baseline and the 28-day period preceding 12 weeks after the last dose
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Percentage Change From Baseline in Countable Seizure Frequency at 24 Weeks After the Last Dose
時間枠: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%.
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Baseline and the 28-day period preceding 24 weeks after the last dose
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Clinical Global Impression of Change (CGI-C) Score at 24 Weeks After the Last Dose
時間枠:24 weeks after the last dose
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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.
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24 weeks after the last dose
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Caregiver Global Impression of Change (CaGI-C) Score at 24 Weeks After the Last Dose
時間枠: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.
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24 weeks after the last dose
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Change From Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Expressive Communication Raw Score at 24 Weeks After the Last Dose
時間枠:Baseline and 24 weeks after the last dose
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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.
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Baseline and 24 weeks after the last dose
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Change From Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Receptive Communication Raw Score at 24 Weeks After the Last Dose
時間枠: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.
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Baseline and 24 weeks after the last dose
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Change From Baseline in Age-Appropriate Wechsler Intelligence Scale Score at 24 Weeks After the Last Dose
時間枠:Baseline and 24 weeks after the last dose
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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.
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Baseline and 24 weeks after the last dose
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2025年12月22日
一次修了 (推定)
2027年12月31日
研究の完了 (推定)
2027年12月31日
試験登録日
最初に提出
2026年6月16日
QC基準を満たした最初の提出物
2026年6月23日
最初の投稿 (実際)
2026年6月30日
学習記録の更新
投稿された最後の更新 (実際)
2026年6月30日
QC基準を満たした最後の更新が送信されました
2026年6月23日
最終確認日
2025年12月1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
- 2025-LCYJ-187
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?
いいえ
IPD プランの説明
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.
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
いいえ
米国FDA規制機器製品の研究
いいえ
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。