Abstract Details

Title 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)

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P8 - Poster Session 8 (8:00 AM-9:00 AM)

Poster/Presentation
Number 9-007

Objective

To evaluate safety and efficacy of EPX-100 as adjunctive therapy in patients with LGS.

Background EPX-100 is a 1^st-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.

Authors/Disclosures
Amit Ray, MD, FAAN (Northshore University Hospital) PRESENTER	Dr. Ray has received personal compensation for serving as an employee of Harmony Biosciences. Dr. Ray has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Harmony Biosciences. Dr. Ray has or had stock in Harmony Biosciences.
George G. Nomikos, MD, PhD	Dr. Nomikos has received personal compensation for serving as an employee of Harmony Biosciences.
Grant Runyan, PhD	Mr. Runyan has received personal compensation for serving as an employee of Harmony Biosciences. Mr. Runyan has stock in Harmony Biosciences.
Juby Philip	Mrs. Philip has nothing to disclose.
David Albers, PhD (Harmony Biosciences)	Dr. Albers has received personal compensation for serving as an employee of Harmony Biosciences. Dr. Albers has or had stock in Harmony Biosciences.
Scott C. Baraban, PhD	Prof. Baraban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Harmony Biosciences.
Kumar Budur, MD (AbbVie)	Kumar Budur, MD has received personal compensation for serving as an employee of Harmony Biosciences. Kumar Budur, MD has stock in Abbvie.

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