A Study to Evaluate the Safety and Pharmacokinetics of RC001 in Children With Dravet Syndrome
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
Przegląd badań
Status
Status
Warunki
Warunki
Interwencja / Leczenie
Interwencja / Leczenie
Szczegółowy opis
Typ studiów
Typ studiów
Zapisy (Szacowany)
Zapisy
Faza
Faza
- Wczesna faza 1
Kontakty i lokalizacje
Kontakt w sprawie studiów
Kontakt w sprawie studiów
- Nazwa: Weiping Liao, Ph.D
- Numer telefonu: 086-020-34152498
- E-mail: wpliao@163.net
Lokalizacje studiów
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Guangdong
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Guangzhou, Guangdong, Chiny, 510120
- Rekrutacyjny
- The second Affiliated Hospital of Guangzhou Medical University
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Kontakt:
- Juan Chen
- Numer telefonu: 086-020-34153599
- E-mail: gyeylcyjzx@163.com
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Kryteria uczestnictwa
Kryteria kwalifikacji
Kryteria kwalifikacji
Wiek uprawniający do nauki
- Dziecko
- Dorosły
Akceptuje zdrowych ochotników
Opis
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.
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Nielosowe
- Model interwencyjny: Zadanie dla jednej grupy
- Maskowanie: Brak (otwarta etykieta)
Liczba ramion
Broń i interwencje
Grupa uczestników / ArmGrupa uczestników / Arm |
Interwencja / LeczenieInterwencja / Leczenie |
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Eksperymentalny: 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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Eksperymentalny: 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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Co mierzy badanie?
Podstawowe miary wyniku
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Ramy czasowe: 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)
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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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Miary wyników drugorzędnych
Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Maximum Observed Plasma Concentration (Cmax) of RC001
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: Baseline and the 28-day period preceding 24 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 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
Ramy czasowe: 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
Ramy czasowe: 24 weeks after the last dose
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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
Ramy czasowe: 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
Ramy czasowe: 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 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
Ramy czasowe: 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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Współpracownicy i badacze
Sponsor
Sponsor
Współpracownicy
Współpracownicy
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
Rozpoczęcie studiów
Zakończenie podstawowe (Szacowany)
Zakończenie podstawowe
Ukończenie studiów (Szacowany)
Ukończenie studiów
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Pierwszy wysłany
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia wysłana aktualizacja
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
Inne numery identyfikacyjne badania
Inne numery identyfikacyjne badania
- 2025-LCYJ-187
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Opis planu IPD
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
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