Study on the Effectiveness and Safety of Fenfluramine Hydrochloride for Patients with CDKL5 Deficiency Disorder

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What is this study about?

This clinical trial is focused on studying a rare genetic condition known as CDKL5 Deficiency Disorder (CDD). This disorder is characterized by seizures, developmental delays, and motor difficulties. The study is testing a treatment called Fenfluramine hydrochloride, which is also referred to by its code name, ZX008. This medication is being evaluated to see if it can help reduce seizures in individuals with CDD. Participants in the study will receive either the medication or a placebo, which looks like the medication but does not contain the active ingredient.

The purpose of the study is to assess the effectiveness and safety of ZX008 in treating CDD. The study will be conducted in two parts. In the first part, participants will be randomly assigned to receive either ZX008 or a placebo. This part of the study is designed to be “double-blind,” meaning neither the participants nor the researchers will know who is receiving the actual medication. After this phase, all participants will have the opportunity to receive ZX008 in an “open-label” extension, where everyone knows they are receiving the medication. The study will last for a total of 74 weeks, during which the participants’ seizure activity and overall health will be closely monitored.

The study aims to demonstrate that ZX008 is more effective than a placebo in reducing seizures and improving the overall condition of individuals with CDD. Additionally, the study will gather information on the long-term safety and tolerability of the medication. Participants will be required to attend regular visits to monitor their progress and report any changes in their condition. This trial is an important step in finding a potential treatment for those affected by CDKL5 Deficiency Disorder.

1 Joining the study

Upon joining the study, the participant will be assessed to confirm eligibility based on specific criteria related to CDKL5 deficiency disorder. This includes a confirmed mutation in the CDKL5 gene, a clinical diagnosis with epilepsy onset in the first year of life, and motor and developmental delays.

The participant must be between 1 to 35 years old and have a history of not achieving seizure control despite previous or current use of two or more anti-epileptic treatments.

2 Initial assessment and baseline establishment

The participant will undergo an initial assessment to establish a baseline for seizure frequency and other health parameters. This includes ensuring that all current epilepsy treatments are stable prior to the start of the trial.

3 Titration period

During the titration period, the participant will begin taking the study medication, fenfluramine hydrochloride, in the form of an oral solution. The dosage will be adjusted to reach a target of 0.8 mg/kg/day.

The participant will be monitored closely to assess the medication’s effects and any side effects.

4 Maintenance period

Once the target dosage is reached, the participant will continue taking the medication at this fixed dose. The maintenance period is designed to evaluate the long-term effectiveness and safety of the treatment.

The participant’s seizure frequency and overall health will be regularly monitored.

5 Open-label extension

After completing the initial phases of the study, the participant may enter an open-label extension phase. In this phase, all participants receive the active medication, fenfluramine hydrochloride, to further assess its long-term safety and effectiveness.

Regular follow-ups will continue to monitor the participant’s response to the treatment.

Who Can Join the Study?

The patient must have a confirmed change in the CDKL5 gene that is known to cause problems, and must have been diagnosed with CDKL5 Deficiency Disorder (CDD), which includes having epilepsy that started in the first year of life, along with movement and developmental delays.
The patient can be a boy or girl, aged between 1 and 35 years old. However, patients aged 1 to less than 2 years can only join the study after a safety review is done for older patients.
The patient must have tried at least 2 different treatments for seizures in the past or currently, but still not have full control over their seizures.
The patient must currently be using at least one treatment for seizures, which could be medication, a special diet called the ketogenic diet, or devices like vagus nerve stimulation (VNS) or responsive neurostimulation (RNS).
All treatments for epilepsy, including medications, VNS, RNS, and the ketogenic diet, must be stable before joining the study. This means the patient should have been using VNS or RNS for at least 6 months, and medications or the ketogenic diet for at least 4 weeks before the study starts.
At the start of the study, the patient’s caregiver must report that the patient has at least 4 countable motor seizures per week. These are specific types of seizures that last about 3 seconds or longer.
The patient or their parent/legal guardian must provide written consent to participate in the study. If applicable, the patient must also agree to participate.
The patient and their caregiver must be willing and able to follow the study requirements, which include keeping a diary, attending scheduled visits, and managing the study medication properly.

Who Cannot Join the Study?

Patients who do not have a confirmed diagnosis of CDKL5 Deficiency Disorder cannot participate. This is a specific genetic condition that affects brain development.
Patients who are not within the specified age range for the study cannot participate. The study includes both children and adults.
Patients who are not able to follow the study procedures or take the study medication as required cannot participate.
Patients who have other medical conditions that might interfere with the study or make participation unsafe cannot participate.
Patients who are currently participating in another clinical trial cannot participate.
Patients who have had a recent change in their medication for CDKL5 Deficiency Disorder cannot participate.
Patients who are pregnant or breastfeeding cannot participate.
Patients who have a history of drug or alcohol abuse cannot participate.
Patients who have a known allergy to the study medication or its ingredients cannot participate.
Patients who have a serious heart condition cannot participate.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
Centro Hospitalar Universitario Sao Joao E.P.E.	Porto	Portugal

Other Sites

Site Name	City	Country
IRCCS Istituto Giannina Gaslini	Genoa	Italy
Azienda Ospedaliero Universitaria Di Modena	Modena	Italy
Azienda Ospedaliera Universitaria Meyer IRCCS	Florence	Italy
Hospital Sant Joan De Deu Barcelona	Esplugues De Llobregat	Spain
Universitaetsklinikum Schleswig-Holstein AöR	Kiel	Germany
Hospital De Santa Maria E.P.E.	Lisbon	Portugal
Epilepsie Instellingen Nederland Stichting	Zwolle	The Netherlands
Gesellschaft Fuer Epilepsieforschung	Bielefeld	Germany
Hospital La Milagrosa S.A.	Madrid	Spain
Universita’ Degli Studi Di Verona	Verona	Italy
Universidade De Santiago De Compostela	Santiago De Compostela	Spain
Kepler Universitaetsklinikum GmbH	Linz	Austria
Ospedale Pediatrico Bambino Gesu’	Rome	Italy
Children’s Health Ireland	Dublin	Ireland
Cunnkvrqe Uggeklrtrupfle Snrkyxjtv	Woluwe-Saint-Lambert	Belgium
Darmwleg Knwi	Kehl	Germany
Cmkt Uxhnojawtg Hwzcoraz	Cork	Ireland
Sfotvl Koiecw Vmatjpkafa Se &esbi Cpn Ka	Vogtareuth	Germany
Uoawdzgbpo Ox Analifn	Edegem	Belgium

Trial status

Country	Status	Recruitment Start
Austria	Not recruiting	18.07.2023
Belgium	Not recruiting	18.07.2023
Germany	Not recruiting	18.07.2023
Ireland	Not recruiting	18.07.2023
Italy	Not recruiting	18.07.2023
Portugal	Not recruiting	18.07.2023
Spain	Not recruiting	18.07.2023
The Netherlands	Not recruiting	18.07.2023

Trial locations

Investigated drugs:

Fenfluramine Hydrochloride

ZX008 is being studied as a treatment for individuals with CDKL5 Deficiency Disorder (CDD). This medication is being tested to see if it can help improve symptoms when used alongside other treatments. The study aims to determine if ZX008 is more effective than a placebo in providing relief and improving the overall condition of both children and adults with CDD. Additionally, the trial will evaluate the safety and how well patients tolerate ZX008 over both short and long periods. The study also looks at how the body processes the medication to ensure it is safe and effective for long-term use.

Investigated diseases:

CDKL5 deficiency disorder

CDKL5 Deficiency Disorder – CDKL5 Deficiency Disorder is a rare genetic condition caused by mutations in the CDKL5 gene, which is crucial for normal brain development and function. This disorder primarily affects the nervous system, leading to severe developmental delays and early-onset seizures. Individuals with CDKL5 Deficiency Disorder often experience difficulties with motor skills, communication, and may have intellectual disabilities. The condition is typically diagnosed in infancy or early childhood, as symptoms usually appear within the first few months of life. Seizures associated with this disorder can be difficult to control and may vary in type and frequency. Additionally, individuals may exhibit autistic-like behaviors and have gastrointestinal issues.

Trial ID:

2023-506269-78-00

Protocol code:

ZX008-2103/EP0216

NCT ID:

NCT05064878

Trial Phase:

Therapeutic confirmatory (Phase III)

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Study on the Effectiveness and Safety of Fenfluramine Hydrochloride for Patients with CDKL5 Deficiency Disorder

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