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

NCT06118255 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: EP02132022-502359-75U1111-1289-2867
• Study Type: interventional
• Target: 25
• Locations: 5 countries
• Sites: 12

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.

Conditions

Dravet Syndrome

Keywords

Dravet syndrome; pediatrics; Fintepla; fenfluramine

Outcome Measures

Primary Outcomes (6)

• Change from Baseline in QT interval corrected by Fridericia (QTcF) at Visit 13 (End of Treatment/Early Termination (EOT/ET))

  QTcF is the QT interval corrected for heart rate according to Fridericia's formula. Higher values correspond to prolongation of QT interval.

  Week 52 (Visit 13; EOT/ET), compared to Baseline

• Occurrence of a treatment-emergent (ie, post-Baseline through Visit 13 [EOT/ET]) result which meets the FDA case definition of drug associated valvulopathy

  Drug associated valvulopathy refers to aortic regurgitation with severity mild or greater and/or mitral regurgitation with severity moderate or greater.

  From post-Baseline (Day 1) through Visit 13 (EOT/ET) (up to 52 weeks)

• Occurrence of treatment-emergent (ie, post-Baseline through Visit 13 [EOT/ET]) clinically confirmed valvular heart disease (VHD)

  Clinically confirmed VHD is an aortic regurgitation with mild or greater severity and/or a mitral regurgitation with moderate or greater severity.

  From post-Baseline (Day 1) through Visit 13 (EOT/ET) (up to 52 weeks)

• Change from Baseline in body weight (Z-score) at each visit

  Body weight (Z-score) refers to the number of standard deviations a participant's body weight lies from the mean, when compared to others of similar gender and age.

  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

• Change from Baseline in recumbent length (Z-score) at each visit

  Recumbent length (Z-score) refers to the number of standard deviations a participant's body weight lies from the mean, when compared to others of similar gender and age.

  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

• Occurrence of a clinically significant abnormality on the neurological examination at each visit

  A complete neurological examination will be conducted by the investigator for each participant covering cranial nerves, muscle strength and tone, reflexes, coordination, sensory function, and gait.

  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 (8)

• Percentage change from the Baseline Period (ie, Baseline) in monthly (28 days) countable motor seizure frequency (CMSF), during Weeks 9 through 20

  During Weeks 9 to 20, compared to Baseline

• Percentage change from Baseline in CMSF during Weeks 1 through 20

  During Weeks 1 to 20, compared to Baseline

• Percentage change from Baseline in CMSF during the Treatment Period (Week 1 through the EOT/ET Visit)

  During the Treatment Period (Week 1 through EOT/ET) (up to 52 weeks), compared to Baseline

• 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

  At Week 20

• Achievement of a CGI-I rating of "much improved" or "very much improved" as assessed by the parent/caregiver at Week 20

  At Week 20

Study Arms (1)

Fenfluramine Open-label

EXPERIMENTAL

All study participants will initiate fenfluramine hydrochloride (HCl) treatment at 0.2 mg/kg/day in the Dose-Finding Period and may be up-titrated to a maximum of 0.8 mg/kg/day based on the Investigators discretion. The dose of fenfluramine HCl can be flexibly titrated during the Maintenance Period. Study participants, who discontinue early will participate in the Taper Period. All participants will complete an End of Treatment (EOT) Visit.

Drug: fenfluramine

Interventions

fenfluramine DRUG

The study drug, fenfluramine HCl, is an oral solution to be administered in equal doses twice daily (BID). It will be based on the current dose and participant's weight (kg).

Also known as: Fintepla

Fenfluramine Open-label

Eligibility Criteria

• Age: 1 Year - 23 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Participant has a known hypersensitivity to fenfluramine hydrochloride (HCl) or any of the excipients in the study drug
• 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 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

Sponsors & Collaborators

• UCB BIOSCIENCES, Inc.: lead

Study Sites (12)

Ep0213 105

Memphis, Tennessee, 38103-2800, United States

Location

Ep0213 107

Dallas, Texas, 75207, United States

Location

Ep0213 103

Seattle, Washington, 98105, United States

Location

Ep0213 502

Brussels, Belgium

Location

Ep0213 501

Edegem, Belgium

Location

Ep0213 303

Bielefeld, Germany

Location

Ep0213 202

Florence, Italy

Location

Ep0213 203

Genova, Italy

Location

Ep0213 201

Roma, Italy

Location

Ep0213 204

Roma, Italy

Location

Ep0213 403

Glasgow, United Kingdom

Location

Ep0213 401

London, United Kingdom

Location

MeSH Terms

Conditions

Epilepsies, Myoclonic

Interventions

Fenfluramine

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• UCB Cares

  001 844 599 2273

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2023
• First Posted: November 7, 2023
• Study Start: May 21, 2024
• Primary Completion (Estimated): September 3, 2026
• Study Completion (Estimated): December 16, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data from this study may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.

Locations

BE (2); GB (2); DE (1); IT (4); US (3)