Treatment of Refractory Infantile Spasms With Fenfluramine

Study Overview
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Brief Summary
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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.

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

Conditions
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Infantile Spasm

Intervention / Treatment
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* Drug: Fenfluramine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 36 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fenfluramine treatment<br>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<br>* Open-label<br>* Other names: Fenfluramine Hydrochloride;|

What is the study measuring?
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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 |