A Study to Evaluate the Safety and Pharmacokinetics of RC001 in Children With Dravet Syndrome

NCT07675746 | Recruiting Early Phase 1

• 1 other identifier: 2025-LCYJ-187
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Dravet Syndrome (DS)

Keywords

Dravet syndrome; Developmental and epileptic encephalopathy; RC001; Oligonucleotide drugs; ADAR RNA editing; SCN1A gene

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (10)

• Maximum Observed Plasma Concentration (Cmax) of RC001

  From first dose to last dose up to 12 weeks

• Time to Maximum Observed Plasma Concentration (Tmax) of RC001

  From first dose through 12 weeks

• Trough Concentration (Ctrough) of RC001 in Cerebrospinal Fluid

  Prior to each dose through 12 weeks

• Percentage Change From Baseline in Countable Seizure Frequency at 12 Weeks After the Last Dose

  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

  Baseline and the 28-day period preceding 24 weeks after the last dose

Study Arms (2)

Dose Escalation Cohort

EXPERIMENTAL

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

Fixed Dose Cohort

EXPERIMENTAL

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

Interventions

RC001 injection-Dose Escalation Cohort DRUG

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.

Dose Escalation Cohort

RC001 injection-Fixed Dose Cohort DRUG

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.

Fixed Dose Cohort

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

The Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510120, China

RECRUITING

MeSH Terms

Conditions

Epilepsies, Myoclonic; Generalized Epilepsy With Febrile Seizures Plus, Type 2

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Central Study Contacts

Weiping Liao, Ph.D

CONTACT

086-020-34152498; wpliao@163.net

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study; no parties are masked.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two-part sequential design (Dose escalation followed by fixed dose treatment)

Study Record Dates

• First Submitted: June 16, 2026
• First Posted: June 30, 2026
• Study Start: December 22, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 30, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)