Fenfluramine for Dravet Syndrome

Recruiting at 2 trial locations

Overseen By Rebecca Rochowiak

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Colorado, Denver

Must not be taking: Sodium channel blockers

Disqualifiers: Mitral regurgitation, Aortic regurgitation, Failure to thrive, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if fenfluramine can reduce seizures in children under 24 months with Dravet syndrome, a severe form of epilepsy linked to a specific genetic mutation. Fenfluramine has shown promise in older children by significantly reducing seizure occurrences. The trial seeks children who have tried other anti-seizure medications that don't block sodium channels and have experienced prolonged seizures. Participants should not have heart valve issues or significant weight problems, as the medication can affect appetite and growth. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants must have failed at least one anti-seizure medication that is not a sodium channel blocker, which might suggest some medications could be continued.

What is the safety track record for fenfluramine?

Research has shown that fenfluramine is generally safe for treating Dravet syndrome. In earlier studies, patients taking fenfluramine experienced a significant reduction in seizures, with one study showing a 70% decrease in monthly convulsive seizures compared to those taking a placebo.

Long-term studies have provided important information about its safety. These studies followed patients over extended periods and found that fenfluramine was usually well-tolerated. The most common side effects included decreased appetite, tiredness, and diarrhea, but these were typically mild.

Fenfluramine is already approved for children aged 2 and older with Dravet syndrome, indicating its safety for this age group. The current study aims to assess its safety and effectiveness in younger children under 24 months, so more children can benefit from this potentially life-changing treatment. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Fenfluramine is unique because it offers a novel approach to managing Dravet Syndrome. Unlike standard treatments that primarily focus on controlling seizures through conventional antiepileptic drugs, fenfluramine works by modulating serotonin pathways, which can reduce seizure frequency and severity. This dual mechanism of action, targeting both serotonin and traditional seizure pathways, has researchers excited as it presents a new frontier in potentially improving quality of life for patients. Additionally, the dosing flexibility of fenfluramine allows for tailored treatment plans, which could lead to better individualized care.

What is the effectiveness track record for fenfluramine in treating Dravet syndrome?

Research has shown that fenfluramine, the treatment under study in this trial, can help treat Dravet syndrome, a severe type of epilepsy. One study found it reduced convulsive seizures by 74.9%, compared to a 19.2% reduction in the placebo group. Notably, 16% of children taking fenfluramine experienced no seizures at all. Another study reported a 79% drop in monthly seizures over 14 weeks. Fenfluramine is already approved for children aged 2 and older and might be equally effective for younger children. ^{2 3 6 7 8}

Who Is on the Research Team?

Kelly Knupp, MD

Principal Investigator

University of Colorado, Denver

Joseph Sullivan, MD

Principal Investigator

University of California, San Francisco

Elaine Wirrel, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for infants and toddlers under 24 months old with Dravet Syndrome, a severe form of epilepsy. To join, they must have the genetic markers associated with this condition and cannot be effectively treated with common anti-seizure medications that block sodium channels.

Inclusion Criteria

I have submitted my echocardiogram results for review.

Each subject will be reviewed by the multi-PIs to ensure agreement that the subject has Dravet syndrome

I have tried an anti-seizure medication other than lamotrigine, oxcarbazepine, carbamazepine, or eslicarbazepine without success.

Exclusion Criteria

I am not experiencing significant, unexplained weight loss or failure to thrive.

I do not have significant heart valve issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fenfluramine with doses ranging from 0.2 mg/kg/day to 0.7 mg/kg/day, administered twice daily

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fenfluramine

Trial Overview The trial tests fenfluramine's safety in young children with Dravet Syndrome. Fenfluramine has shown promise in older children by significantly reducing seizures. This study will explore if similar benefits occur in those under two years old.

How Is the Trial Designed?

Group I: Fenfluramine Experimental Treatment 1 Intervention

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.

Fenfluramine is already approved in United States, European Union for the following indications:

Approved in United States as Fintepla for:

• Seizures associated with Dravet syndrome
• Seizures associated with Lennox-Gastaut syndrome

Approved in European Union as Fintepla for:

• Seizures associated with Dravet syndrome
• Seizures associated with Lennox-Gastaut syndrome

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

UCB Pharma

Industry Sponsor

Trials

345

Recruited

110,000+

Jean-Christophe Tellier

UCB Pharma

Chief Executive Officer since 2015

MD specialized in Rheumatology

Prof. Dr. Iris Löw-Friedrich

UCB Pharma

Chief Medical Officer since 2004

MD, PhD

Published Research Related to This Trial

In a small observational study of 12 patients with Dravet syndrome, 70% achieved seizure freedom while on fenfluramine, which is significantly higher than the typical 16% seen in other long-term follow-ups.

While some patients experienced mild cardiac valve thickening, it was not clinically significant, suggesting that fenfluramine may be a safe and effective add-on therapy for managing seizures in Dravet syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful use of fenfluramine as an add-on treatment for Dravet syndrome. Ceulemans, B., Boel, M., Leyssens, K., et al.[2022]

Fenfluramine (Fintepla®) has been shown to be a highly effective and safe treatment for Dravet Syndrome (DS), demonstrating significant seizure reduction in three phase III studies involving placebo controls.

The anticonvulsive mechanism of fenfluramine appears to be primarily serotonergic, and it is generally well tolerated, although dose adjustments are needed when used with stiripentol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A critical evaluation of fenfluramine hydrochloride for the treatment of Dravet syndrome. Schoonjans, AS., Ceulemans, B.[2022]

In a clinical trial involving 119 patients with Dravet syndrome, fenfluramine at a dose of 0.7 mg/kg per day resulted in a significant 74.9% reduction in convulsive seizure frequency compared to a 19.2% reduction in the placebo group, demonstrating its efficacy as a treatment option.

Fenfluramine was generally well tolerated, with no evidence of serious heart issues like valvular heart disease or pulmonary arterial hypertension, indicating a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. Lagae, L., Sullivan, J., Knupp, K., et al.[2022]

In a real-world study involving 149 patients with Dravet syndrome, fenfluramine treatment led to a significant reduction in monthly convulsive seizure frequency, with 62% of patients under 6 years, 53% aged 6-17, and 50% aged 18 and older achieving a ≥75% reduction after 3 months.

Fenfluramine was generally well-tolerated, with the most common side effects being loss of appetite (21%) and somnolence (16%), and no serious cardiovascular issues like valvular heart disease or pulmonary artery hypertension were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An examination of the efficacy and safety of fenfluramine in adults, children, and adolescents with Dravet syndrome in a real-world practice setting: A report from the Fenfluramine European Early Access Program. Guerrini, R., Specchio, N., Aledo-Serrano, Á., et al.[2022]

In a clinical trial involving 87 children with Dravet syndrome, fenfluramine significantly reduced monthly convulsive seizure frequency by 54% compared to placebo, indicating its efficacy as an additional treatment for patients with poor seizure control.

Fenfluramine was generally well tolerated, with no evidence of serious heart-related side effects, making it a promising new treatment option for managing seizures in Dravet syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fenfluramine for Treatment-Resistant Seizures in Patients With Dravet Syndrome Receiving Stiripentol-Inclusive Regimens: A Randomized Clinical Trial. Nabbout, R., Mistry, A., Zuberi, S., et al.[2023]

Fenfluramine, originally developed as an appetite suppressant, has shown promising antiepileptic effects in treating seizures associated with Dravet syndrome, a severe form of epilepsy in infants.

Preliminary results from a Phase 3 trial indicate that fenfluramine may be a highly effective and well-tolerated treatment option for children with Dravet syndrome, who often experience frequent and severe seizures despite other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized treatment approaches: Fenfluramine, a novel antiepileptic medication for the treatment of seizures in Dravet syndrome. Polster, T.[2020]

Citations

1. finteplahcp.com finteplahcp.com/dravet-efficacy

FINTEPLA® Efficacy in Clinical Trials – Dravet Syndrome Figure showing that FINTEPLA® reduced convulsive seizure frequency by 79.4% from baseline over 14. *P value vs placebo.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11997923/

Fenfluramine treatment for Dravet syndrome: Long term ... A 52% mean reduction (range 11%–94%) in epilepsy‐related hospital contacts from baseline to the end of the treatment period was reported in 75% ...

3. ucb-usa.com ucb-usa.com/stories-media/UCB-U-S-News/detail/article/epilepsia-publishes-final-analysis-open-label-extension

Epilepsia Publishes Final Analysis of Open-Label ... Efficacy outcomes showed a sustained reduction in MCSF with FINTEPLA in the mITT population of 324 patients, with a median change from Day 1 to ...

4. fintepla.com fintepla.com/dravet-syndrome

Results in Dravet syndrome | FINTEPLA® (fenfluramine) In a 14-week clinical study, FINTEPLA reduced monthly seizures by 79%. This is compared with only 16% for patients taking a placebo.

5. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2791918

Efficacy and Safety of Fenfluramine for the Treatment ... More patients in the active treatment groups achieved a 25% or greater reduction in drop seizures compared with placebo (27 of 87 [31%]) during ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12169399/

Long‐term safety and effectiveness of fenfluramine in ... We analyzed the long‐term safety and effectiveness of fenfluramine (FFA) in patients with Dravet syndrome (DS) in an open‐label extension (OLE) study.

7. ucb-usa.com ucb-usa.com/stories-media/UCB-U-S-News/detail/article/final-analysis-of-open-label-extension-ole-study-of-fintepla-fenfluramine-in-lennox-gastaut-syndrome-published-in-epilepsy-and-behavior.

Final analysis of open-label extension (OLE) study ... Long-term safety and effectiveness of fenfluramine in children and adults with Dravet syndrome. Epilepsia. 2025;66(6):1919-32. Specchio N ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03936777

NCT03936777 | A Study to Investigate the Long-Term ... This is an international, multicenter, open-label, long-term safety study of ZX008 in patients with epileptic encephalopathy, including Dravet syndrome or ...