Fenfluramine for Dravet Syndrome

(ORCHID Trial)

Recruiting at 18 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

20 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug fenfluramine for Dravet syndrome?

Research shows that fenfluramine, originally used as an appetite suppressant, has been found to be effective in reducing seizures in patients with Dravet syndrome. Clinical trials and studies have demonstrated its efficacy and safety, leading to its approval by health authorities for this condition. ^{1 2 3 4 5}

Is fenfluramine safe for humans?

Fenfluramine has been shown to be a safe treatment option for Dravet syndrome, although it was previously withdrawn from the market due to possible heart-related side effects. Recent studies and trials have demonstrated its safety and effectiveness for this condition, leading to its approval by health authorities. ^{1 2 3 4 5}

What makes the drug fenfluramine unique for treating Dravet syndrome?

Fenfluramine is unique for treating Dravet syndrome because it was originally developed as an appetite suppressant and works through a serotonergic mechanism (affecting serotonin levels in the brain). It has shown potential in reducing seizures in patients who do not respond well to conventional treatments, making it a promising option for this difficult-to-treat condition. ^{2 3 4 5 6}

What is the purpose of this trial?

The primary purpose of this study is evaluate the safety and tolerability of fenfluramine hydrochloride (HCl) 0.2 to 0.8 mg/kg/day in infants 1 year to less than 2 years of age with Dravet syndrome.

Research Team

UCB Cares

Principal Investigator

001 844 599 2273

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

A critical evaluation of fenfluramine hydrochloride for the treatment of Dravet syndrome. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Successful use of fenfluramine as an add-on treatment for Dravet syndrome. [2022]

3. United States 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. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Fenfluramine for Treatment-Resistant Seizures in Patients With Dravet Syndrome Receiving Stiripentol-Inclusive Regimens: A Randomized Clinical Trial. [2023]