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

Official title

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

Overview

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.

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.

Interventions

• 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.
• 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.

Primary outcome measures

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Time frame: From first dose to 24 weeks after the last dose]
• Number of Participants With Serious Adverse Events (SAEs) [Time frame: From signing informed consent to 24 weeks after the last dose]
• Number of Participants With Clinically Significant Abnormalities in Vital Signs [Time frame: From baseline to 24 weeks after the last dose]
• Number of Participants With Clinically Significant Abnormal Physical Examination Findings [Time frame: From baseline to 24 weeks after the last dose]
• Number of Participants With Clinically Significant Abnormal Laboratory Test Results [Time frame: From baseline to 24 weeks after the last dose]
• Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings [Time frame: From baseline to 24 weeks after the last dose]

Secondary outcome measures (10)

• Maximum Observed Plasma Concentration (Cmax) of RC001 [Time frame: From first dose to last dose up to 12 weeks]
• Time to Maximum Observed Plasma Concentration (Tmax) of RC001 [Time frame: From first dose through 12 weeks]
• Trough Concentration (Ctrough) of RC001 in Cerebrospinal Fluid [Time frame: Prior to each dose through 12 weeks]
• Percentage Change From Baseline in Countable Seizure Frequency at 12 Weeks After the Last Dose [Time frame: 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 [Time frame: 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 [Time frame: 24 weeks after the last dose]
• Caregiver Global Impression of Change (CaGI-C) Score at 24 Weeks After the Last Dose [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Baseline and 24 weeks after the last dose]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital of Guangzhou Medical University — Guangzhou

Identifiers

NCT: NCT07675746 · 2025-LCYJ-187

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗