Clinical trial NCT06118255: 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
Official title: Open-Label, Single-Arm, Phase 3 Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Fenfluramine (Hydrochloride) in Infants 1 Year to Less Than 2 Years of Age With Dravet Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Dravet Syndrome
Keywords: Dravet syndrome
pediatrics
Fintepla
fenfluramine
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2023-11-07
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is evaluate the safety and tolerability of fenfluramine hydrochloride (HCl) 0.2 to 0.8 mg/kg/day in infants 1 year to less than 2 years of age with Dravet syndrome.


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

Primary outcomes:
measure: Change from Baseline in QT interval corrected by Fridericia (QTcF) at Visit 13 (End of Treatment/Early Termination (EOT/ET))
timeFrame: Week 52 (Visit 13; EOT/ET), compared to Baseline
measure: Occurrence of a treatment-emergent (ie, post-Baseline through Visit 13 [EOT/ET]) result which meets the FDA case definition of drug associated valvulopathy
timeFrame: From post-Baseline (Day 1) through Visit 13 (EOT/ET) (up to 52 weeks)
measure: Occurrence of treatment-emergent (ie, post-Baseline through Visit 13 [EOT/ET]) clinically confirmed valvular heart disease (VHD)
timeFrame: From post-Baseline (Day 1) through Visit 13 (EOT/ET) (up to 52 weeks)
measure: Change from Baseline in body weight (Z-score) at each visit
timeFrame: Week 1 (Visit 3), Week 4 (Visit 5), Week 8 (Visit 7), Week 12 (Visit 8), Week 16 (Visit 9), Week 20 (Visit 10), Week 26 (Visit 11), Week 39 (Visit 12), Week 52 (Visit 13), Postdose Safety Follow-Up (Visit 14), compared to Baseline
measure: Change from Baseline in recumbent length (Z-score) at each visit
timeFrame: Week 1 (Visit 3), Week 4 (Visit 5), Week 8 (Visit 7), Week 12 (Visit 8), Week 16 (Visit 9), Week 20 (Visit 10), Week 26 (Visit 11), Week 39 (Visit 12), Week 52 (Visit 13), Postdose Safety Follow-Up (Visit 14), compared to Baseline
measure: Occurrence of a clinically significant abnormality on the neurological examination at each visit
timeFrame: Week 1 (Visit 3), Week 4 (Visit 5), Week 8 (Visit 7), Week 12 (Visit 8), Week 16 (Visit 9), Week 20 (Visit 10), Week 26 (Visit 11), Week 39 (Visit 12), Week 52 (Visit 13), Postdose Safety Follow-Up (Visit 14), compared to Baseline
Secondary outcomes:
measure: Percentage change from the Baseline Period (ie, Baseline) in monthly (28 days) countable motor seizure frequency (CMSF), during Weeks 9 through 20
timeFrame: During Weeks 9 to 20, compared to Baseline
measure: Percentage change from Baseline in CMSF during Weeks 1 through 20
timeFrame: During Weeks 1 to 20, compared to Baseline
measure: Percentage change from Baseline in CMSF during the Treatment Period (Week 1 through the EOT/ET Visit)
timeFrame: During the Treatment Period (Week 1 through EOT/ET) (up to 52 weeks), compared to Baseline
measure: Achievement of a Clinical Global Impression - Improvement (CGI-I) rating of "much improved" or "very much improved" as assessed by the Principal Investigator at Week 20
timeFrame: At Week 20
measure: Achievement of a CGI-I rating of "much improved" or "very much improved" as assessed by the parent/caregiver at Week 20
timeFrame: At Week 20
measure: Steady-state maximum plasma concentration (Cmax) of fenfluramine and norfenfluramine at Week 12
timeFrame: At Week 12
measure: Steady-state minimum plasma concentration (Cmin) of fenfluramine and norfenfluramine at Week 12
timeFrame: At Week 12
measure: Area under the plasma concentration time curve from time zero to 24 hours (AUC0 24) for steady-state fenfluramine and norfenfluramine at Week 12
timeFrame: At Week 12
Other outcomes:
Locations:
city: Orange
country: United States
facility: Ep0213 106
state: California
city: Winston-Salem
country: United States
facility: Ep0213 102
state: North Carolina
city: Memphis
country: United States
facility: Ep0213 105
state: Tennessee
city: Dallas
country: United States
facility: Ep0213 107
state: Texas
city: Seattle
country: United States
facility: Ep0213 103
state: Washington
city: Bruxelles
country: Belgium
facility: Ep0213 502
city: Edegem
country: Belgium
facility: Ep0213 501
city: Bielefeld
country: Germany
facility: Ep0213 303
city: Jena
country: Germany
facility: Ep0213 301
city: Florence
country: Italy
facility: Ep0213 202
city: Genova
country: Italy
facility: Ep0213 203
city: Roma
country: Italy
facility: Ep0213 201
city: Roma
country: Italy
facility: Ep0213 204
city: Barcelona
country: Spain
facility: Ep0213 601
city: Madrid
country: Spain
facility: Ep0213 603
city: Madrid
country: Spain
facility: Ep0213 604
city: Pamplona
country: Spain
facility: Ep0213 602
city: Glasgow
country: United Kingdom
facility: Ep0213 403
city: London
country: United Kingdom
facility: Ep0213 401
Study officials:
affiliation: 001 844 599 2273
name: UCB Cares
role: STUDY_DIRECTOR
References: