Efficacy and Safety of Relutrigine in Pediatric Participants with SCN2A- and SCN8A-related Developmental and Epileptic Encephalopathies: Pivotal EMBOLD Cohort 2 Study
Samata Kamireddy1, Silvana Frizzo1, Brian Spar1, Kelley Del Real1, Poppy Guest1, Dharit Patel1, Henry Jacotin1, Steven Petrou1, Marcio Souza1, Linda Laux2, Douglas Smith3, Antonio Gil-Nagel4, Eric Segal5
1Praxis Precision Medicines, 2Ann and Robert H Lurie Children’s Hospital of Chicago, 3Minnesota Epilepsy Group, 4Hospital Ruber Internacional, 5Northeast Regional Epilepsy Group
Objective:
Pivotal study evaluating the efficacy, safety, tolerability, and pharmacokinetics of relutrigine, a precision sodium channel modulator, in pediatric participants with early onset SCN2A- and SCN8A-related developmental and epileptic encephalopathies (DEEs).
Background:
DEEs are devastating pediatric epilepsies, characterized by frequent, refractory seizures, global developmental impairment and increased early mortality. Relutrigine is a differentiated functional state sodium channel modulator with demonstrated superior selectivity for disease-state hyperexcitability, a known cause of seizure manifestation in all DEEs. Building on the promising, well-tolerated efficacy observed in Cohort 1 through open label extension (OLE), Cohort 2 of the ongoing EMBOLD study (NCT05818553) is designed to confirm efficacy and further define the therapeutic profile of relutrigine in a larger pediatric population.
Design/Methods:
Multicenter, double-blind, placebo-controlled, randomized study, followed by OLE, enrolling eligible male and female participants aged 1-18 years, inclusive, diagnosed with early onset SCN2A-DEE or SCN8A-DEE. Cohort 2 participants are randomized (1:1) to receive relutrigine 1mg/kg/day for 16 weeks, or relutrigine 1mg/kg/day for 12 weeks and matching placebo daily for 4 weeks, with timing of placebo administration blinded for both participants and investigators. Part A (randomized, double-blind) includes Screening, Double-Blind Treatment, and Safety Follow-up periods, while Part B (OLE) includes Treatment and Safety Follow-up periods. Participants have the option to undergo study assessments in a hybrid fashion (in-clinic and at-home) or fully decentralized (home-based).
Results:
The primary endpoint is the change from baseline in motor seizure frequency. Secondary endpoints will include incidence and severity of TEAEs, and further efficacy assessments based on seizure freedom and clinical (CGI) and caregiver (CgGI) global impression of improvement and severity.
Conclusions:
Cohort 2 represents the pivotal, registration-enabling phase of the EMBOLD study in patients with SCN2A- and SCN8A-DEE. Efficacy and safety data are expected to further define relutrigine’s therapeutic potential and support its advancement as a precision sodium channel modulator for broad DEEs.
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