Fenfluramine for Dravet Syndrome

(ORCHID Trial)

Not currently recruiting at 17 trial locations

Overseen By UCB Cares

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: UCB BIOSCIENCES, Inc.

Must be taking: Antiseizure medications

Must not be taking: Cannabidiol, THC, Anorectics, others

Disqualifiers: Cardiovascular disease, Glaucoma, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and comfort of using fenfluramine to treat infants with Dravet syndrome, a severe form of epilepsy. Researchers will evaluate the treatment's effectiveness in reducing seizures in these young patients. Parents of infants diagnosed with Dravet syndrome, who are on stable anti-seizure medications and have drug-resistant epilepsy, might consider joining this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment for Dravet syndrome.

Will I have to stop taking my current medications?

The trial requires that participants stay on at least one anti-seizure medication at a stable dose. However, certain medications like cannabidiol (except Epidiolex), THC, and some others must be stopped before starting the trial. If you're taking any of these, you'll need a washout period (time without taking them) of at least 5 half-lives before starting the study drug.

Is there any evidence suggesting that fenfluramine is likely to be safe for infants with Dravet syndrome?

Research has shown that fenfluramine is generally safe for people with Dravet syndrome. In earlier studies, participants taking fenfluramine required 52% fewer hospital visits due to epilepsy, indicating fewer severe seizures.

Another study examined long-term safety and found fenfluramine safe for both children and adults with Dravet syndrome. Some side effects occurred, but they were usually mild, such as decreased appetite, tiredness, and diarrhea.

The FDA has already approved fenfluramine for treating Dravet syndrome in older children, which suggests its safety for younger children, like those in the current study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Dravet syndrome?

Fenfluramine is unique because it offers a novel approach to treating Dravet Syndrome by enhancing serotonin release and modulating receptor activity, which is different from the common seizure medications like valproate and clobazam. Researchers are excited about fenfluramine because it has shown potential to significantly reduce seizure frequency, offering hope for better management of this challenging condition. Additionally, its flexible dosing options allow for personalized treatment, which could lead to improved outcomes for patients.

What evidence suggests that fenfluramine might be an effective treatment for Dravet syndrome?

Research has shown that fenfluramine effectively treats Dravet syndrome. Studies have found it can reduce convulsive seizures by up to 79% compared to pre-treatment levels. In one study, patients taking fenfluramine experienced significantly fewer seizures than those on a placebo, which only saw a 16% reduction. Long-term studies also support these findings, indicating that the reduction in seizures persists over time. This evidence suggests fenfluramine is a promising option for managing seizures in Dravet syndrome. In this trial, all participants will receive fenfluramine, starting at 0.2 mg/kg/day, with potential adjustments based on the investigator's discretion. ^{6 7 8 9 10}

Who Is on the Research Team?

UCB Cares

Principal Investigator

001 844 599 2273

Are You a Good Fit for This Trial?

This trial is for infants aged 1 to less than 2 years with Dravet syndrome, weighing at least 8 kg. They must have a diagnosis according to ILAE criteria and be on stable epilepsy medication for at least 4 weeks. Participants need to have had at least four motor seizures in the month before starting the study.

Inclusion Criteria

I am between 1 and 2 years old.

I am either male or female.

I have had 4 or more seizures in the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Finding Period

Participants initiate fenfluramine hydrochloride (HCl) treatment at 0.2 mg/kg/day and may be up-titrated to a maximum of 0.8 mg/kg/day based on the Investigator's discretion

Up to 12 weeks

Maintenance Period

The dose of fenfluramine HCl can be flexibly titrated during this period

Up to 40 weeks

Taper Period

Participants who discontinue early will participate in the Taper Period

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 study tests the safety and tolerability of fenfluramine hydrochloride, given daily in doses ranging from 0.2 to 0.8 mg/kg, in young children with Dravet syndrome.

How Is the Trial Designed?

Group I: Fenfluramine Open-label Experimental Treatment 1 Intervention

All study participants will initiate fenfluramine hydrochloride (HCl) treatment at 0.2 mg/kg/day in the Dose-Finding Period and may be up-titrated to a maximum of 0.8 mg/kg/day based on the Investigators discretion. The dose of fenfluramine HCl can be flexibly titrated during the Maintenance Period. Study participants, who discontinue early will participate in the Taper Period. All participants will complete an End of Treatment (EOT) Visit.

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?

UCB BIOSCIENCES, Inc.

Lead Sponsor

Trials

28

Recruited

7,200+

Published Research Related to This Trial

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 (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 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]

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]

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 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]

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/PMC9813053/

Fenfluramine for Treating Dravet Syndrome: An Evidence ... The results of these trials were that participants receiving fenfluramine had greater reductions in convulsive seizure frequency (CSF) per 28 days compared to ...

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 In a 14-week clinical study, FINTEPLA reduced monthly seizures by 79%. This is compared with only 16% for patients taking a placebo.

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/epi.18342

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.

6. finteplahcp.com finteplahcp.com/dravet-safety

FINTEPLA® Dravet Safety & Adverse Reactions Learn about the safety and effectiveness of FINTEPLA® in patients with Dravet syndrome from 2 randomized, double-blind, placebo-controlled studies.

7. 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.

8. 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 ...

9. 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 ...

10. 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% ...