Report design/methods of MOMENTUM, a Phase III, randomized study to explore if adjunctive lorcaserin can reduce convulsive seizure frequency in DS.

DS is a severe refractory childhood-onset epilepsy. Open-label studies with the 5-HT2C agonist lorcaserin support its efficacy in controlling convulsive seizures in DS.

MOMENTUM comprises a Core Study (Pre-randomization screening/baseline [4-weeks]; randomization [stratified by history of fenfluramine use and weight; 14-week Treatment; 4-week Follow-up]) and Open-Label Extension (OLEx) Phases [12-week Treatment; 4-week Follow-up]). Eligibility criteria: DS diagnosis; aged ≥2 years; ≥4 convulsive seizures during Pre-randomization; receiving ≥1 anti-seizure medication. Exclusion criteria: presence of another progressive neurological disease; received lorcaserin (4-weeks) and/or fenfluramine (2-months) before Screening; previous lack of efficacy with lorcaserin/fenfluramine; recent or concomitant use of serotonergic drugs or monoamine oxidase inhibitors; enrolled in another clinical study. Patients will receive lorcaserin (oral suspension)/placebo twice daily. Target dose for weights 10–<20, 20–<40, and ≥40 kg will be 5, 10, and 20 mg/day, respectively. Based on tolerability, lorcaserin can be increased to 10/20 mg/day for patients weighing 10–<20/20–<40 kg, respectively during the first 2 weeks of treatment. Patients completing the Core Study can enter the OLEx and long-term Expanded Access Program (Study 405; NCT04457687). Core Study primary endpoint: change in convulsive seizure frequency/28 days. Secondary endpoints: convulsive seizures 50% responder/seizure-freedom rates; lorcaserin pharmacokinetics; treatment-emergent adverse events. Exploratory endpoints: Clinical Global Impression of Change; quality of life; change in frequency of total seizures/non-convulsive seizures/per seizure type. History of epilepsy-related genetic mutations will be collected. Safety assessments: vital signs; weight; ECG; clinical laboratory tests; echocardiography.

MOMENTUM will provide data on adjunctive lorcaserin as a potential therapy in this difficult-to-treat population.

Funding: Eisai Inc.