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
Panoramica dello studio
Stato
Stato
Condizioni
Condizioni
Intervento / Trattamento
Intervento / Trattamento
Descrizione dettagliata
Tipo di studio
Tipo di studio
Iscrizione (Stimato)
Iscrizione
Fase
Fase
- Prima fase 1
Contatti e Sedi
Contatto studio
Contatto studio
- Nome: Weiping Liao, Ph.D
- Numero di telefono: 086-020-34152498
- Email: wpliao@163.net
Luoghi di studio
-
-
Guangdong
-
Guangzhou, Guangdong, Cina, 510120
- Reclutamento
- The second Affiliated Hospital of Guangzhou Medical University
-
Contatto:
- Juan Chen
- Numero di telefono: 086-020-34153599
- Email: gyeylcyjzx@163.com
-
-
Criteri di partecipazione
Criteri di ammissibilità
Criteri di ammissibilità
Età idonea allo studio
- Bambino
- Adulto
Accetta volontari sani
Descrizione
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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Numero di armi
Armi e interventi
Gruppo di partecipanti / ArmGruppo di partecipanti / Arm |
Intervento / TrattamentoIntervento / Trattamento |
|---|---|
|
Sperimentale: 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.
|
|
Sperimentale: 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.
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
Misure di risultato secondarie
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of RC001
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
Collaboratori e investigatori
Sponsor
Sponsor
Collaboratori
Collaboratori
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Inizio studio
Completamento primario (Stimato)
Completamento primario
Completamento dello studio (Stimato)
Completamento dello studio
Date di iscrizione allo studio
Primo inviato
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Primo Inserito
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento pubblicato
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
Altri numeri di identificazione dello studio
- 2025-LCYJ-187
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .