A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Fenfluramine (Hydrochloride) in Infants 1 Year to Less Than 2 Years of Age With Dravet Syndrome

Launched by UCB BIOSCIENCES, INC. · Nov 2, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a medication called fenfluramine hydrochloride (HCl) to see how safe it is and how well it can be tolerated in infants aged 1 to less than 2 years who have Dravet syndrome. Dravet syndrome is a severe form of epilepsy that often does not respond well to standard treatments. The trial aims to determine if fenfluramine can help these young children manage their seizures better while also ensuring that the medication is safe for them.

To be eligible for this study, infants must be between 1 and 2 years old, diagnosed with Dravet syndrome, and currently taking at least one other anti-seizure medication that has been stable for at least four weeks. Participants must also have a history of seizures that have not been controlled by other medications. Parents or guardians can expect regular check-ups and monitoring throughout the study to track any side effects and how well the medication is working. It’s important to note that certain health conditions may prevent participation, so a thorough health evaluation will be conducted before enrollment.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Participant is ≥1 to \<2 years of age as of the day of the first administration of study drug
• • Participant has a documented diagnosis or likely diagnosis of Dravet syndrome according to the International League Against Epilepsy (ILAE) criteria and as agreed by the Epilepsy Study Consortium (ESC)
• • Participant must be currently receiving ≥1 concomitant anti seizure medication (ASM) at a stable dose for ≥4 weeks prior to the Screening Visit and is expected to remain stable throughout the study. Rescue medications for seizures are not counted towards the total number of ASMs
• • Participant must have drug resistant epilepsy as defined as a history of failure of adequate trials of 2 tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom
• • Participants must have ≥1 countable motor seizures (CMS) during the Baseline Period. The CMS include distinct seizures of generalized tonic-clonic, bilateral clonic, focal motor, bilateral tonic, atonic (drop), bilateral tonic/atonic, or focal to bilateral tonic-clonic type. If the participant fails to have ≥1 qualifying seizures in 28 days, the Baseline Period may be extended by an additional 14 days with Sponsor approval. Participants with an extended Baseline Period must still have ≥1 CMS in the 28 days immediately prior to the day of the first administration of study drug
• • Body weight is ≥8 kg
• • Males and females
• Exclusion Criteria:
• • Participant has a known hypersensitivity to fenfluramine hydrochloride (HCl) or any of the excipients in the study drug
• • Participant has an exclusionary cardiovascular or cardiopulmonary abnormality based on echocardiogram (ECHO), electrocardiogram (ECG), or physical examination and is not approved for entry by the central cardiac reader
• • Participant has a diagnosis of pulmonary arterial hypertension
• • Participant has a clinically significant medical condition, including chronic obstructive pulmonary disease, interstitial lung disease, or portal hypertension, or has had clinically relevant symptoms or a clinically significant illness currently or in the 4 weeks prior to the Screening Visit, other than epilepsy, that in the opinion of the Investigator would negatively impact study participation, collection of study data, or pose a risk to the participant
• • Participant has current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke, severe ventricular arrhythmias, or clinically significant structural cardiac abnormality, including but not limited to mitral valve prolapse, atrial or ventricular septal defects, patent ductus arteriosus, and patent foramen ovale with reversal of shunt. (Note: Patent foramen ovale or a bicuspid aortic valve are not considered exclusionary.)
• • Participant has a current or past history of glaucoma
• • Participant has moderate to severe hepatic impairment, assessed based on the Child-Pugh classification system
• • Participant has moderate to severe renal impairment (estimated glomerular filtration rate \<50 mL/min/1.73 m\^2 calculated with the updated Bedside Schwartz equation for children
• • QT interval corrected (QTc) \>450 msec
• • Participant is taking \>4 concomitant ASMs
• • Participant is receiving concomitant treatment with cannabidiol other than Epidiolex/Epidyolex or is being actively treated with tetrahydrocannabinol (THC) or any marijuana product for any condition
• • Participant is receiving concomitant therapy with any of the following: centrally-acting anorectic agents; monoamine-oxidase inhibitors; any centrally-acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; other centrally-acting noradrenergic agonists, including atomoxetine; or cyproheptadine. Disallowed medications are subject to washout of ≥5 half-lives before the first day of study drug administration
• • Participant is currently receiving another investigational product(s) or has received another investigational product within 30 days or within \<5 times the half-life of that investigational product, whichever is longer, prior to the Screening Visit
• • Participant has previously been treated with Fintepla (fenfluramine HCl) prior to the Screening Visit