Long-term Safety Evaluation of Fenfluramine Hydrochloride as Adjunctive Therapy in Patients with Myoclonic Astatic Epilepsy (Doose Syndrome)

The primary objective of this study is to monitor the individual long-term **safety** and efficacy of low-dose **Fenfluramine** (0.4 or 0.8 mg/kg/day, with a maximum of 30.0 mg/day) as an add-on therapy in patients with Myoclonic Astatic Epilepsy, also known as Doose Syndrome. This objective is clinically relevant as it aims to evaluate the sustained safety profile and therapeutic benefits of Fenfluramine in managing this specific type of epilepsy, which is characterized by myoclonic and atonic seizures. Understanding the long-term effects of Fenfluramine is crucial for optimizing treatment strategies and improving patient outcomes in this population.

The clinical trial involves participants diagnosed with **myoclonic-astatic epilepsy**, focusing on monitoring the long-term safety and efficacy of low-dose Fenfluramine as an add-on therapy. The study population includes both male and female subjects, aged between 1 and 17 years. The sponsor has not provided the total number of participants. Participants were selected based on their current enrollment in the FFA-MAE study and must have demonstrated a clinically meaningful benefit from Fenfluramine in a prior trial. This benefit is defined as at least a 50% reduction in the total number of seizures compared to baseline. Subjects are required to be on at least one additional antiepileptic drug alongside Fenfluramine. The trial does not specifically target a vulnerable population, and no particular lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.

The clinical trial is designed as an open-label extension study to monitor the long-term safety and efficacy of **fenfluramine hydrochloride** as an add-on therapy in patients with **myoclonic-astatic epilepsy**. The trial is categorized as a Phase 4 study and is not considered low intervention. The primary objective is to assess the change in the number and frequency of countable seizures compared to the baseline visit of the previous FFA-MAE study, alongside monitoring safety through adverse events, laboratory measurements, vital signs, physical examinations, 12-lead electrocardiograms (ECGs), Doppler echocardiograms (ECHOs), and body weight.

The trial will involve participants who are currently enrolled in the FFA-MAE study, aged between 1 and 17 years, and have demonstrated a clinically meaningful benefit from fenfluramine in the prior trial. Participants must receive at least one additional antiepileptic drug (AED) alongside fenfluramine. The study will exclude any participants who do not meet these criteria. The trial is expected to last until November 2026, with recruitment having started in November 2021.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the inclusion criteria. Follow-up visits will be scheduled to monitor the ongoing safety and efficacy of the treatment. The end-of-study visit will conclude the participant's involvement, assessing the overall outcomes of the treatment. The expected length of participant involvement is up to 60 months, with conditions for early termination including withdrawal of consent, adverse events, or any other reason deemed necessary by the investigator.

The clinical trial involves the administration of **Fintepla 2.2 mg/ml oral solution**, which contains the active substance **fenfluramine hydrochloride**. This experimental medication is provided in the form of an oral solution and is administered orally. The dosing regimen for this study involves a low dose of fenfluramine, specifically 0.4 or 0.8 mg/kg/day, with a maximum allowable dose of 30.0 mg/day. The treatment period is set for a maximum of 60 days. The medication is produced by UCB PHARMA S.A. and is classified under the ATC code N03AX26. The study aims to monitor the long-term safety and efficacy of fenfluramine as an add-on therapy in patients with Myoclonic Astatic Epilepsy, also known as Doose Syndrome.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of the experimental medication, Fintepla. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed regimen. The trial is designed as an open-label extension study, allowing for the observation of the medication's effects over an extended period. The study does not include any additional devices or characteristics related to the administration of the medication.

Efficacy in this clinical trial will be assessed by evaluating the change in the number and frequency of countable seizures in patients with **Myoclonic Astatic Epilepsy** (Doose-Syndrome) receiving Fenfluramine as an add-on therapy. The primary efficacy endpoint involves comparing the individual seizure counts and frequencies to the baseline visit of the previous FFA-MAE study, which was conducted before the onset of Fenfluramine treatment. This assessment will provide insights into the therapeutic impact of Fenfluramine on seizure reduction.