Fenfluramine for Dravet Syndrome

Recruiting at 2 trial locations

Overseen By Rebecca Rochowiak

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Colorado, Denver

Must not be taking: Sodium channel blockers

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

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Dravet syndrome is a genetic epilepsy associated with pathogenic variants in SCN1A that codes for Nav1.1, a protein necessary for sodium channels. Children with Dravet syndrome classically present in the first year of life with prolonged seizures, often hemiclonic and in the setting of fever or temperature changes such as getting in or out of bath water. Many anti-seizure medications are sodium channel blockers and exacerbate seizures in this patient population. This creates some limitations in medication choices for this patient population. Recently fenfluramine was approved for use in Dravet syndrome for people 2 years and older. Randomized studies demonstrated a 74.9% reduction of convulsive motor seizures compared to 19.2% in the placebo group. Additionally, 16% of children treated with fenfluramine were seizure free. Fenfluramine is likely to be as effective in children under the age of 2 years. The current study has proposed a treatment protocol to allow access to fenfluramine for children under 24 months of age.

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 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 highly effective in reducing seizures in patients with Dravet syndrome, a severe form of epilepsy. Clinical trials and studies have demonstrated its safety and efficacy, 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Fenfluramine has been shown to be a safe treatment option for Dravet syndrome, although it was previously withdrawn from the market due to possible heart-related side effects.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}

How is 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), which is different from conventional antiepileptic drugs. It has shown promising results in reducing seizures in patients who do not respond well to other treatments. ^{1 2 3 5 6}

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

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Fenfluramine (Anti-epileptic)

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.

Participant Groups

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.

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

Findings from Research

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]

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

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

2. England pubmed.ncbi.nlm.nih.gov

Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. [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. England pubmed.ncbi.nlm.nih.gov

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

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

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