Fenfluramine for Rett Syndrome

Not yet recruiting at 1 trial location
UC
Overseen ByUCB Cares
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether fenfluramine hydrochloride can help individuals with Rett syndrome, a rare genetic disorder affecting brain development. Researchers aim to determine if this medication is more effective than a placebo (a harmless pill with no active drug) in improving Rett syndrome symptoms. Ideal candidates for this trial have a diagnosis of typical or classic Rett syndrome, a known genetic mutation linked to the disorder, and have not recently experienced a decline in movement, speech, or social skills. As a Phase 3 trial, this is the final step before potential FDA approval, offering participants a chance to contribute to a treatment nearing widespread availability.

Is there any evidence suggesting that fenfluramine hydrochloride is likely to be safe for humans?

Research has shown that fenfluramine hydrochloride, the treatment under study for Rett syndrome, has a good safety record in other conditions. The FDA has already approved it for treating certain types of epilepsy, indicating its general safety. Studies involving Rett syndrome patients found that fenfluramine can significantly reduce the number of seizures, offering hope for those with difficult-to-treat seizures.

Common side effects include fever, a runny nose, and loss of appetite, which are usually mild and manageable. Importantly, long-term studies of fenfluramine in other conditions, such as Dravet and Lennox-Gastaut syndromes, have not identified any new safety issues over time. This consistent safety data is reassuring for its use in Rett syndrome.12345

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

Unlike other treatments for Rett Syndrome, which primarily focus on managing symptoms through therapies and medications like antiepileptic drugs, fenfluramine hydrochloride offers a novel approach. Researchers are excited about fenfluramine because it has a unique mechanism of action that modulates serotonin levels in the brain, potentially addressing the core neurological issues of the syndrome. This could lead to improvements beyond symptom management, offering a new avenue of hope for more profound therapeutic benefits.

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

Research has shown that fenfluramine hydrochloride may help treat Rett syndrome. In some studies, three out of four patients experienced a significant reduction in seizure frequency, with two patients seeing their seizures reduced by more than half. Another study found that seizures decreased by 75-90% after three months of treatment. In this trial, participants will receive either fenfluramine hydrochloride or a placebo during a double-blind period, followed by an open-label treatment period with fenfluramine hydrochloride. Fenfluramine is already approved for use in other severe epilepsy conditions, suggesting it might also be effective for Rett syndrome. Early results highlight its potential to manage difficult-to-treat seizures in people with Rett syndrome, offering hope for better symptom control.12346

Who Is on the Research Team?

UC

UCB Cares

Principal Investigator

0018445992273

Are You a Good Fit for This Trial?

This trial is for males and females aged 5 to 35 with classic Rett Syndrome caused by a MECP2 gene mutation. Participants must not have lost walking, hand use, speech, or social skills. A legal guardian must be able to give consent.

Inclusion Criteria

I have classic Rett Syndrome as defined by the 2010 criteria.
Participant has a Rett Syndrome Clinical Severity Scale (RTT-CSS) rating of 10 to 36 inclusive
Participant has a Clinical Global Impression-Severity (CGIS) score of ≥4
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Exclusion Criteria

I have not had lymphoma, leukemia, or other cancers in the past 5 years, except certain skin cancers.
Participant has clinically significant medical conditions such as COPD, interstitial lung disease, portal hypertension, need for invasive mechanical ventilation, or clinically relevant symptoms or illness within 4 weeks prior to Screening that impact study participation or pose risk
Participant has clinically significant abnormality in vital signs per Investigator
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Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fenfluramine hydrochloride or placebo for 14 weeks in a double-blind period, including titration and maintenance, followed by a 2-week double-blind transition period.

16 weeks

Open-label Extension

Participants receive fenfluramine hydrochloride for 52 weeks in an open-label treatment period. Participants may continue treatment until alternative access is available.

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including an 8-day taper for those discontinuing without continued access.

26 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Fenfluramine Hydrochloride

Trial Overview

The study compares fenfluramine hydrochloride (a medication) against a placebo in people with Rett Syndrome to see if the drug helps more than no active treatment. Participants are randomly assigned to either group.

How Is the Trial Designed?

2

Treatment groups

Experimental Treatment

Placebo Group

Group I: fenfluramine hydrochlorideExperimental Treatment1 Intervention
Group II: PlaceboPlacebo Group1 Intervention

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Who Is Running the Clinical Trial?

UCB BIOSCIENCES, Inc.

Lead Sponsor

Trials
28
Recruited
7,200+

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/41724124/

Use of fenfluramine in MECP2-related Rett syndrome

Results: Three out of four patients experienced a significant reduction in seizure frequency, with > 50% reduction in two cases. Tonic-clonic ...

International Rett Syndrome Foundation

Fenfluramine, marketed under the name FINTEPLA®, is currently FDA-approved to treat several epilepsy syndromes and recently reported positive ...

preliminary evidence on the use of fenfluramine in patients ...

Overall seizure reduction was 75-90% after 3 months of fenfluramine treatment, with one patient being seizure-free. Clinically meaningful ...

Fenfluramine (Fintepla)

Dravet Syndrome, Study to evaluate the safety and effectiveness of Fenfluramine as adjunct therapy in children and young adults with Dravet Syndrome, Phase 3 ...

Fenfluramine reduces hard-to-treat seizures in 3 girls with ...

The therapy specifically reduced seizures in three out of four girls with Rett syndrome who had not responded to several prior anti-seizure ...

NCT03355209 | A Study to Investigate the Efficacy and ...

A Study to Investigate the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) as an Adjunctive Therapy in Children and Adults With Lennox-Gastaut ...