Treatment of Refractory Infantile Spasms With Fenfluramine

A Phase II Study of Fenfluramine for Treatment of Refractory Infantile Spasms

This is a phase II clinical trial in which children with refractory infantile spasms (also called epileptic spasms or West syndrome) will be treated with fenfluramine, to evaluate efficacy, safety, and tolerability. Patients with infantile spasms that have not responded to treatment with vigabatrin and ACTH we will be invited to participate. Study participants will undergo baseline video-EEG, receive treatment with fenfluramine for 21 days, and then undergo repeat video-EEG to determine effectiveness. Patients with favorable response will have the opportunity to continue treatment for up to 6 months.

Study Overview

• Status: Recruiting
• Conditions: Infantile Spasm
• Intervention / Treatment: Drug: Fenfluramine

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Angelyque Lorenzana, MA; Phone Number: 714-509-8972; Email: alorenzana@choc.org
• Study Contact Backup: Name: Virginia Allhusen, PhD; Email: vallhusen@choc.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Not yet recruiting
      • UCLA Health
      • Contact: Angela L. Martinez; Phone Number: 310-206-7630; Email: angelamartinez@mednet.ucla.edu
      • Principal Investigator: Shaun A Hussain, MD
    • Orange, California, United States, 92868
      • Recruiting
      • Children's Hospital of Orange County
      • Contact: Daniel Shrey, MD; Email: dshrey@choc.org
      • Contact: Angelyque Lorenzana; Phone Number: 714-509-8972; Email: alorenzana@choc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children ages 12 to 36 months, inclusive
• Clinical diagnosis of infantile spasms
• Continued epileptic spasms despite adequate treatment with ACTH and vigabatrin.

Exclusion Criteria:

• Significant preexisting cardiovascular disease
• Exposure to any cannabinoid product within 14 days of screening
• Initiation or dose-titration of any second-line treatment for infantile spasms in the 14 days prior to screening.
• Implantation of a vagal nerve simulator within 14 days of screening
• Initiation and maintenance of the ketogenic diet within 3 months of screening

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 treatment; Open label treatment with fenfluramine. Dosage will be titrated to 0.8 mg/kg/day, for an initial duration of 21 days. Patients with favorable response will have an option to continue treatment for up to 6 months.	Drug: Fenfluramine; Open-label; Other Names: Fenfluramine Hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electroclinical response (Efficacy)	Number of participants with resolution of epileptic spasms and hypsarrhythmia (if present at baseline) after 21 days of treatment, as determined by overnight video-electroencephalography (EEG) evaluation and caregiver seizure diary.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Computational electroencephalography response (Efficacy)	Median and range of response quantified using the probability-weighted response index (PWRI), a novel computational electroencephalography measure of hypsarrhythmia burden.	12 months
Incidence of treatment emergent adverse events (Safety and tolerability)	Detailed accounting of all treatment-emergent adverse events, including number of participants with clinically-significant valvulopathy and/or pulmonary hypertension, as determined by echocardiography.	12 months

Collaborators and Investigators

• Sponsor: Children's Hospital of Orange County
• Investigators: Principal Investigator: Daniel Shrey, MD, Children's Hospital of Orange County

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 21, 2020
• First Submitted That Met QC Criteria: February 26, 2020
• First Posted (Actual): February 28, 2020

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Neurologic Manifestations; Neuromuscular Manifestations; Epilepsy; Spasms, Infantile; Spasm; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Fenfluramine
• Other Study ID Numbers: ZX008-IS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No