Thank you for your interest in the GEMZ Study—a phase 3, randomized, doubleblind, placebo controlled, fixed-dose, multicenter study to examine the efficacy and safety of ZX008 in patients with CDKL5 deficiency disorder followed by an open-label extension.
The GEMZ Study is a 2-part multicenter trial. Part 1 is a 20-week randomized, double-blind, placebo-controlled, fixed-dose study to examine the efficacy and safety of ZX008 as an adjunctive therapy (to existing concomitant treatment with antiepileptic treatments) in children and adults with a CDD diagnosis and uncontrolled seizures.
Part 1 of the study consists of the following stages: Baseline Period (4 weeks including the Screening Visit and baseline observation), Titration Period (2 weeks), Maintenance Period (12 weeks), and a 2-week Transition Period (2 weeks) to the open-label starting dose.
Part 2 is a 54-week, open-label, flexible-dose, long-term extension for participants who complete Part 1. Part 2 includes an Open-Label Extension Treatment Period (52 weeks) with a Taper Period of 2 weeks and a subsequent 6-months cardiac safety follow-up period.
The primary study analysis to evaluate the efficacy and safety of fenfluramine hydrochloride in children and adults with CDD will be based on Part 1 data in all randomized participants.
Fenfluramine hydrochloride (or the placebo in part 1) is administered orally as aqueous solution twice a day (BID) with or without food.
The study is looking to enroll a total of about 80 study participants at approximately 70 studsites globally, including North America, Europe, Middle East, and Asia.
The primary outcome measures of the study are the median percentage change from the baseline period in monthly countable motor seizure frequency, and the median percentage change from the baseline period in monthly countable motor seizure frequency during the combined titration and maintenance periods in the fenfluramine hydrochloride group compared with the placebo group.
The main inclusion and exclusion criteria are:
- The patient has a confirmed pathogenic or likely pathogenic mutation in the CDKL5 gene and a clinical diagnosis of CDD with epilepsy onset in the first year of life, plus motor and developmental delays.
- The patient is aged 2 to 35 years, inclusive, as of the day of the Screening Visit.
- The patient must have failed to achieve seizure control despite previous or current use of 2 or more AETs.
- The patient is currently receiving at least 1 concomitant antiseizure treatment: antiseizure medication (ASM), vagus nerve stimulation (VNS), responsive neurostimulation (RNS), or ketogenic diet (KD).
- ll medications or interventions for epilepsy (including VNS, RNS, and KD) must be stable prior to screening and are expected to remain stable throughout the study.
- At the Screening Visit, the parent/caregiver reports that the patient has ≥ 4 countable motor seizures per week.
- The patient does not have a diagnosis of pulmonary arterial hypertension or other clinically significant medical conditions as specified in the study protocol, including but not limited to current or past history of cardiovascular or cerebrovascular disease and severe hepatic impairment.
- The patient is not taking > 4 concomitant ASMs (excluding rescue medications).
- The patient has not previously been treated with Fintepla® (fenfluramine hydrochloride) prior to the Screening Visit.
(Please note that this is not the full list of all in- and exclusion criteria for the study.)
Study participants can continue receiving their normal background antiseizure medication(s) upon enrollment.
The study is listed in the FDA's ClinicalTrials.gov database with the identifier NCT05064878.