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

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.

Study Overview

• Status: Recruiting
• Conditions: Dravet Syndrome (DS)
• Intervention / Treatment: Drug: RC001 injection-Dose Escalation Cohort; Drug: RC001 injection-Fixed Dose Cohort

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Weiping Liao, Ph.D; Phone Number: 086-020-34152498; Email: wpliao@163.net

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • The Second Affiliated Hospital of Guangzhou Medical University
      • Contact: Juan Chen; Phone Number: 086-020-34153599; Email: gyeylcyjzx@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. 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.
3. Documented pathogenic or likely pathogenic variants in the SCN1A gene associated with Dravet syndrome.
4. 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).
5. Use of at least one ASM prior to screening, with a stable dose for at least 4 weeks before screening.
6. 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).
7. Willingness to participate and provision of written informed consent.

Exclusion Criteria:

1. 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.
2. Current maintenance treatment with anti-epileptic drugs primarily acting as sodium channel blockers, including but not limited to carbamazepine, oxcarbazepine, lamotrigine, lacosamide, or rufinamide.
3. Ongoing neuromodulation therapy (e.g., responsive neurostimulation or deep brain stimulation), excluding vagus nerve stimulation (VNS).
4. Receipt of gene therapy or cell therapy within 1 year prior to screening.
5. Receipt of any vaccination within 12 weeks prior to screening.
6. 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.
7. Presence of any severe uncontrolled disease other than Dravet syndrome.
8. History of autoimmune disease, or uncontrolled infectious disease within 1 week prior to screening.
9. History of brain or spinal cord disease (other than epilepsy, Dravet syndrome, or trauma), or history of bacterial meningitis.
10. Spinal deformity or other conditions that may interfere with normal cerebrospinal fluid (CSF) flow, or implantation of a CSF shunt.
11. Pregnant or breastfeeding females.
12. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: RC001 injection-Dose Escalation Cohort; 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.
Experimental: 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.	Drug: RC001 injection-Fixed Dose Cohort; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	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)	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	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	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	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	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of RC001	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	Tmax of RC001 in plasma following intrathecal administration.	From first dose through 12 weeks
Trough Concentration (Ctrough) of RC001 in Cerebrospinal Fluid	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	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	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	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	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	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	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	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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Guangzhou Medical University
• Collaborators: RecoRNA(Guangzhou) Biotechnology Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 16, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 30, 2026

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Dravet syndrome; Developmental and epileptic encephalopathy; RC001; Oligonucleotide drugs; ADAR RNA editing; SCN1A gene
• Additional Relevant MeSH Terms: Epileptic Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epilepsy; Epilepsies, Myoclonic; Generalized Epilepsy With Febrile Seizures Plus, Type 2
• Other Study ID Numbers: 2025-LCYJ-187

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No