Five different types of developmental and epileptic encephalopathies (DEEs): SYNGAP1 and STXBP1 encephalopathies, inv-dup(15) encephalopathy, multifocal or bilateral Malformations of Cortical Development and Continuous Spikes And Waves During Sleep Syndrome. MedDRA version: 21.1 Level: LLT Classification code 10053551 Term: Intractable epilepsy System Organ Class: 100000004852
Conditions
Interventions
Trade Name: Fintepla
Pharmaceutical Form: Oral liquid
INN or Proposed INN: FENFLURAMINE
CAS Number: 404-82-0
Other descriptive name: Fenfluramine hydrochloride
Concentration unit: mg/ml milligram(s)/m
Sponsors
Neurologia Aplicada, SLP
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General inclusion criteria: - Age between 2 and 35 years (both included). - Diagnosis of epilepsy associated with some degree of intellectual disability, starting before 11 years of age. - All patients will have a phenotype consistent with their genetic, electroclinical or neuroimaging diagnosis. Specific inclusion criteria per group: o Group 1: Non-controlled epilepsy after failing at least 3 antiseizure medications, with a minimum of 4 countable seizures with motor semiology per month during the baseline period of 3 months. - Group 1A: Patients with genetic testing showing a pathogenic or likely pathogenic variant in main synaptopathy genes (SYNGAP1 and STXBP1). - Group 1B: Patients with genetic testing showing a pathogenic or likely pathogenic inverted duplication of chromosome 15 [inv-dup (15)]. - Group 1C: Patients with neuroimaging showing multifocal or bilateral malformations of cortical development. o Group 2: Electroclinical diagnosis of Continuous Spikes and Waves during Sleep (CSWS) syndrome, with baseline video-EEG monitoring showing epileptiform activity occupying at least 50% of slow sleep tracing, after failing at least 3 antiseizure medications. Additional inclusion criteria: In addition, all subjects must meet all of the following inclusion criteria to be enrolled into the study: - Subject is male or non-pregnant, non-lactating female. Female subjects of childbearing potential must not be pregnant or breast-feeding. Female subjects of childbearing potential must have a negative urine or serum pregnancy test at screening and during the study. - Receiving at least 1 concomitant antiseizure medications (ASMs) and up to 4 concomitant ASMs, inclusive. KD and VNS are permitted but do not count towards the total number of ASMs. Rescue medications for seizures are not counted towards the total number of ASMs. - All medications or interventions for epilepsy (including ketogenic diet and vagal nerve stimulation) must be stable for at least 4 weeks prior to screening and are expected to remain stable throughout the study. - Subject has been informed of the nature of the study and informed consent has been obtained from the legally responsible parent/guardian. - Subject has provided assent in accordance with Institutional Review Board (IRB)/Ethics Committee requirements, if capable. - Subject’s parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability. Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following exclusion criteria will not be enrolled into the study: - Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study medication. - Subject has only non-motor seizures (such as absences), for group 1. - Subject has pulmonary arterial hypertension. - Subject has current or past history of cardiovascular or cerebrovascular disease. - Subject has current or recent history of Anorexia Nervosa, bulimia, or depression within the prior year that required medical treatment or psychological treatment for a duration greater than 1 month. - Subject has a current or past history of glaucoma. - Subject has moderate or severe renal or hepatic impairment. - Subject 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. - Subject is currently receiving an investigational product. - Subject has participated in another clinical trial within the past 30 days (calculated from that study’s last scheduled visit). - Subject is at imminent risk of self-harm or harm to others. - Subject is unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions. - Subject is institutionalized in a general nursing home (i.e., in a facility that does not provide skilled epilepsy care). - Subject does not have a reliable caregiver who can provide seizure diary information throughout the study. - Subject has a severe clinically significant condition.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Secondary objectives of this study are the analysis of changes in seizure intensity and duration, and "non-epileptic outcomes" such as variations in cognitive activity, level of alertness, impulsivity/self-control, gait stability and other alterations that might be detected during the interview and physical examination.;Primary end point(s): Regarding the goal of evaluating a reduction in seizure frequency and to assess favorable response or lack of favorable response in the selected groups of patients treated with fenfluramine the following will be evaluated: - Percent change in frequency of seizures with motor semiology (both groups) and quantified epileptiform activity during slow sleep (group 2), after 12 weeks of treatment. - Responder rate (percentage of patients experimenting a 50% decrease in seizure frequency -group 1- or quantified epileptiform activity during slow sleep -group 2) after 12 weeks of treatment.;Timepoint(s) of evaluation of this end point: After 12 weeks of treatment.;Main Objective: The main goal is to identify if there is a reduction in seizure frequency in patients comparing before and after treatment with fenfluramine in five specific types of developmental and epileptic encephalopathies (DEEs). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Regarding the secondary goal of assessing changes in seizure intensity and duration, and in non-epileptic outcomes, to assess favorable response or lack of favorable response in the selected groups of patients treated with fenfluramine, the following will be evaluated: - Percent change in seizure intensity scales, executive and behavioral measures, sleep evaluation, functional scales and quality of life measures (for both groups), after 12 weeks of treatment.;Timepoint(s) of evaluation of this end point: After 12 weeks of treatment. | — |
Countries
Spain
Contacts
Public ContactDpt. of Neurology Clinical Trials
Hospital Ruber Internacional
Outcome results
None listed