Assessment of Safety of the Use of Fenfluramine in Children With Dravet Syndrome Under 24 Months of Age

Assessment of Safety of the Use of Fenfluramine in Children With Dravet Syndrome Under the Age of 24 Months

Dravet syndrome is a genetic epilepsy associated with pathogenic variants in SCN1A that codes for Nav1.1, a protein necessary for sodium channels. Children with Dravet syndrome classically present in the first year of life with prolonged seizures, often hemiclonic and in the setting of fever or temperature changes such as getting in or out of bath water. Many anti-seizure medications are sodium channel blockers and exacerbate seizures in this patient population. This creates some limitations in medication choices for this patient population. Recently fenfluramine was approved for use in Dravet syndrome for people 2 years and older. Randomized studies demonstrated a 74.9% reduction of convulsive motor seizures compared to 19.2% in the placebo group. Additionally, 16% of children treated with fenfluramine were seizure free. Fenfluramine is likely to be as effective in children under the age of 2 years. The current study has proposed an intermediate size patient population expanded access protocol to allow access to fenfluramine for children under 24 months of age.

Study Overview

• Status: Recruiting
• Conditions: Dravet Syndrome (DS); Children Under 2 Years
• Intervention / Treatment: Drug: fenfluramine

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Rebecca Rochowiak; Phone Number: 720-777-0717; Email: rebecca.rochowiak@childrenscolorado.org

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
      • Principal Investigator: Kelly Knupp, MD
      • Contact: Rebecca Rochowiak; Phone Number: 720-777-0709; Email: rebecca.rochowiak@childrenscolorado.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Treating physicians must submit a clinical statement of potential benefit, which includes patient's gender, age, diagnosis, genetic pathogenic variant, co-morbidities, seizure history, prior and current therapies, response to prior therapies and reason for request. Echocardiogram (ECHO) results must also be submitted to the lead site prior to final approval. Patients must be between 12 and 23 months old to be eligible. Additional inclusion criteria:

1. SCN1A with a known or presumed pathogenic variant or VUS with a history of prolonged seizure or a clinical diagnosis of Dravet syndrome.
2. Failure of at least one anti-seizure medication that is not a sodium channel blocker (lamotrigine, oxcarbazepine, carbamazepine, eslicarbazepine)

Exclusion Criteria:

1. Patients with mild or greater mitral valve regurgitation and/or trace or greater aortic valve regurgitation will not be eligible for participation. The clinical statement can be submitted first for initial, conditional approval and then ECHO results can be submitted at a later date for final approval.

2. Patients with failure to thrive will not be eligible for participation as fenfluramine can suppress appetite and has a risk for weight loss. Failure to thrive will be evaluated on the following criteria:

   1. Weight less than the 2nd percentile.
   2. Lack of weight gain that crosses two or more of the major percentile lines and is not congruent with length.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Fenfluramine; The dose of FENFLURAMINE for the duration of the Treatment Period will range from 0.2 mg/kg/day to a maximum of 0.7 mg/kg/day, not to exceed a total daily dose of 26 mg/day; for patients concurrently being prescribed stiripentol, the maximum will be 0.4 mg/kg/day, not to exceed a total daily dose of 17 mg/day. Under this treatment plan, FENFLURAMINE will be administered twice daily in equally divided doses, with at least 8 hours and no more than 12 hours between doses in a single day.

Drug: fenfluramine; Clear, cherry flavored oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants that have at least one adverse event	A description of the percentage of participants that have at least one adverse event.	12 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: UCB Pharma
• Investigators: Principal Investigator: Kelly Knupp, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: September 13, 2024
• First Submitted That Met QC Criteria: September 13, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Dravet Syndrome; Fenfluramine; Children under 2 years
• Additional Relevant MeSH Terms: Epileptic Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epilepsy; Epilepsies, Myoclonic; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Fenfluramine
• Other Study ID Numbers: 21-3972

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No