Fenfluramine for Dravet and Lennox-Gastaut Syndromes

No longer recruiting at 165 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Zogenix, Inc.

Must not be taking: Monoamine oxidase inhibitors, serotonin agonists

Disqualifiers: Cardiac valvulopathy, pulmonary hypertension, hepatic impairment, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a medication called ZX008 (Fenfluramine Hydrochloride) for individuals with rare seizure disorders like Dravet syndrome and Lennox-Gastaut syndrome. The goal is to evaluate the long-term safety of ZX008 in managing these severe seizure conditions. Individuals who participated in a related study and have a rare seizure disorder might be suitable for this trial. Participants should not have significant heart or lung issues and should avoid taking certain other medications. As a Phase 3 trial, this is the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications for the trial?

The trial requires that you stop taking certain medications, specifically monoamine oxidase inhibitors, serotonin agonists, serotonin antagonists, and serotonin reuptake inhibitors, at least 14 days before starting the study drug.

Is there any evidence suggesting that ZX008 (Fenfluramine Hydrochloride) is likely to be safe for humans?

In a previous study, fenfluramine (ZX008) was generally well tolerated by patients with Dravet and Lennox-Gastaut syndromes. Research shows that while some patients experienced reduced appetite, most side effects were manageable. Other studies suggest that fenfluramine could be a safe treatment option for these conditions, with long-term evidence supporting its continued use. Overall, participants usually handled the treatment well, though monitoring for side effects remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Dravet and Lennox-Gastaut syndromes?

Unlike the standard treatments for Dravet and Lennox-Gastaut Syndromes, which often include medications like valproate or clobazam, ZX008 (Fenfluramine Hydrochloride) offers a unique approach. This treatment works by modulating serotonin receptors, which is different from the mechanisms of most other anti-seizure drugs. Researchers are excited because ZX008 has shown potential in reducing seizure frequency more effectively, with some patients experiencing significant improvements. Plus, it’s administered as a simple oral solution, making it easy to use and integrate into daily routines.

What evidence suggests that ZX008 might be an effective treatment for Dravet and Lennox-Gastaut syndromes?

Research shows that ZX008, also known as fenfluramine hydrochloride, helps reduce seizures in people with Dravet syndrome and Lennox-Gastaut syndrome. Studies found it can lower the number of convulsive seizures by about 79.4% over 14 weeks, significantly outperforming a placebo. Participants in previous studies tolerated the treatment well and experienced a significant decrease in seizures. Fenfluramine is already approved for treating seizures in these conditions, underscoring its effectiveness. This trial will further evaluate ZX008, presenting a promising option for managing these challenging types of epilepsy. ^{4 6 7 8 9}

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 children and adults with rare seizure disorders like Dravet syndrome or Lennox-Gastaut syndrome, who have completed a prior Zogenix study. Participants must not be pregnant, breastfeeding, have serious liver issues, heart valve problems or pulmonary hypertension, nor take certain medications affecting serotonin within 14 days of the trial.

Inclusion Criteria

You have a rare seizure disorder like epileptic encephalopathy and have finished another Zogenix-sponsored trial with ZX008.

I am a man or a woman not pregnant or breastfeeding.

Satisfactory completion of a core study

Exclusion Criteria

I have a serious heart valve problem or high blood pressure in my lungs.

I haven't taken any depression or migraine medications in the last 14 days.

My liver is not working well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ZX008 (Fenfluramine Hydrochloride) oral solution as an adjunctive therapy for seizures

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Open-label extension

Participants continue to receive ZX008 for an extended period to assess long-term safety

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• ZX008 (Fenfluramine Hydrochloride)

Trial Overview The study tests the long-term safety of ZX008 (Fenfluramine Hydrochloride) oral solution in patients with specific epileptic encephalopathies. It's an international study where all participants receive the drug to see how it affects them over time.

How Is the Trial Designed?

Group I: ZX008 (Fenfluramine Hydrochloride) Experimental Treatment 1 Intervention

ZX008 is supplied as an open-label oral solution.Doses will include up to 0.8 mg/kg/day divided into 2 daily doses, up to a maximum of 30 mg/day (subjects taking concomitant STP will receive up to 0.5 mg/kg/day, up to a maximum of 20 mg/day) in a concentration of 2.5 mg/mL.

ZX008 (Fenfluramine Hydrochloride) is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Fintepla for:

• Dravet syndrome
• Lennox-Gastaut syndrome
• CDKL5 deficiency disorder

Approved in United States as Fintepla for:

• Dravet syndrome
• Lennox-Gastaut syndrome
• CDKL5 deficiency disorder

Approved in Japan as Fintepla for:

• Dravet syndrome
• Lennox-Gastaut syndrome
• CDKL5 deficiency disorder

Who Is Running the Clinical Trial?

Zogenix, Inc.

Lead Sponsor

Trials

25

Recruited

2,600+

Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.

Industry Sponsor

Trials

12

Recruited

1,700+

Citations

1. 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30146701/

A pilot, open-label study of the effectiveness and tolerability ... ZX008 (fenfluramine HCl oral solution) was well tolerated and reduced seizure frequency in Dravet syndrome, prompting this phase 2, open-label, dose-finding ...

3. 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 ... FINTEPLA is indicated for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients 2 years ...

4. finteplahcp.com finteplahcp.com/dravet-efficacy

FINTEPLA® Efficacy in Clinical Trials – Dravet Syndrome FINTEPLA reduced convulsive seizure frequency by 79.4% from baseline over 14 weeks, which is approximately 5 times greater than placebo, in patients with ...

5. epilepsybehavior.com epilepsybehavior.com/article/S1525-5050(25)00493-7/fulltext

long-term impact on patients and caregivers Effectiveness outcomes are reported for the modified intent-to-treat (mITT) population, which included all patients who received at least one dose of ...

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/PMC10310619/

Fenfluramine: A Review in Dravet and Lennox-Gastaut ... 4, oral fenfluramine was generally well tolerated in patients with DS [24–30, 46] or LGS [41, 42], both in the short term (14–15 weeks [24–26, ...

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

Efficacy and Safety of Fenfluramine for the Treatment ... Meaning Findings from this trial suggest that fenfluramine may be a safe and effective treatment option for patients with LGS. Abstract.

9. ema.europa.eu ema.europa.eu/en/documents/product-information/fintepla-epar-product-information_en.pdf

Fintepla, INN-fenfluramin - EMA In the controlled trials of children and young adults with Dravet syndrome 34.7% of fenfluramine-treated patients had an adverse reaction of decreased appetite, ...