A 20-Week Multicenter, Randomized, Double-Blind (DB), Placebo-Controlled, Phase 3 Trial (EPX 100-003) of EPX-100 (Clemizole Hydrochloride) as Adjunctive Therapy in patients with Lennox-Gastaut Syndrome (LGS)
Amit Ray1, George Nomikos1, Grant Runyan1, Juby Philip1, David Albers1, Scott Baraban2, Kumar Budur1
1Harmony Biosciences, 2University of California, San Francisco
Objective:
To evaluate safety and efficacy of EPX-100 as adjunctive therapy in patients with LGS.
Background:
EPX-100 is a 1st-generation antihistamine identified as having antiseizure activity using an innovative and highly predictive zebrafish model for Dravet Syndrome (DS) and LGS [Baraban et al. Nat Commun. 2013;4:2410]. Mechanism of action studies suggest antiseizure effects are due to serotonergic agonist activity. Previous preclinical studies coupled with Phase 1 studies showing an acceptable safety and tolerability profile in humans support further development. LGS is a developmental epileptic encephalopathy characterized by severe cognitive impairment along with multiple seizure types refractory to currently available pharmacologic treatments.
Design/Methods:
Study will enroll patients ≥ 2 years of age with a diagnosis of LGS. After an initial screening visit, patients will enter a 4-week observational phase to assess baseline seizure frequency based on diary recordings of daily seizure activity. Patients must have at least 4 countable major motor (CMMS-28) seizures during this phase. Eligible patients enter a subsequent DB period (4-week titration, 12 weeks maintenance) and are randomly assigned to receive EPX-100 or placebo. Patients who complete the DB period can enter an optional 156-week open-label extension.
Results:
The primary endpoint is the percentage change in CMMS-28 from Baseline Period through the end of DB Period (titration plus maintenance phase) between EPX-100 vs. placebo. Key secondary endpoints include proportion of participants with ≥50% reduction in CMMS-28 from the Baseline Period to the end of the DB Period, percent change in CMMS-28 seizure-free days during the DB Period relative to the Baseline Period and Clinician Global Impression of Change (CGI-C) score at the end of the DB Period. Safety assessments include incidence and severity of adverse events, clinical laboratory tests.
Conclusions:
This is an upcoming Phase 3 study to determine effectiveness and safety of EPX-100 in patients with LGS.
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