Clinical trial • Phase III • Neurology|Rare Disease

fenfluramine hydrochloride for Rett syndrome

Phase III trial of fenfluramine hydrochloride for Rett syndrome.

Overview

Trial Therapeutic Area
Neurology|Rare Disease
Trial Disease
Rett syndrome
Trial Stage
Phase III
Drug Modality
Small molecule
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
16-12-2025
First CTIS Authorization Date
15-04-2026

Trial design

Randomised, open-label, placebo matching < ucb product (zx008, fenfluramine hydrochloride oral solution) > and without active substance (matching placebo); dose/schedule not specified in the provided source-controlled Phase III trial across 29 sites in Belgium, France, Germany and others.

Randomised
Yes
Open Label
Yes
Comparator
Placebo matching < UCB PRODUCT (ZX008, fenfluramine hydrochloride oral solution) > and without active substance (matching placebo); dose/schedule not specified in the provided source
Target Sample Size
139

Eligibility

Recruits 139 paediatric patients.

Vulnerable Population
Vulnerable populations are selected (isVulnerablePopulationSelected = true). The study population includes children/minors (eligible ages 5 to 35 years) with Rett syndrome. Consent is to be provided by a legal representative: "Participant has a legal representative capable of providing signed informed consent on behalf of the participant as described in the protocol..." Caregiver requirements include a consistent caregiver ≥18 years able to complete caregiver assessments. Age-specific subject information and informed consent/assent documents are available (country- and age-stratified ICFs and information sheets for minors, e.g. versions for ages 5-11 and 12-17 are listed among public documents).

Inclusion criteria

  • {"criterion_text":"- Participant has typical or classic Rett Syndrome (RTT) according to the RettSearch Consortium 2010 revised criteria"}
  • {"criterion_text":"- Participant has a documented disease-causing mutation in the methyl-CpG-binding protein 2 (MECP2) gene"}
  • {"criterion_text":"- Participant meets criteria for postregression for at least 6 months prior to Screening, defined as: − No loss or degradation of ambulation (including gait, coordination, or independence of walking/standing); − No loss or degradation of hand function; no loss or degradation of speech (including babbling, words, or previously developed communicative vocalizations); − No loss or degradation of nonverbal communicative or social skills (including eye gaze, using body to indicate communicative intent, or social attentiveness)"}
  • {"criterion_text":"- Participant has an Rett Syndrome Clinical Severity Scale (RTT-CSS) rating of 10 to 36 (inclusive)"}
  • {"criterion_text":"- Participant has a Clinical Global Impression-Severity (CGIS) score of ≥4"}
  • {"criterion_text":"- Participant has a legal representative capable of providing signed informed consent on behalf of the participant as described in the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol."}
  • {"criterion_text":"- Participant is aged 5 to 35 years of age (inclusive) at the time of first administration of investigational intervention."}
  • {"criterion_text":"- Male or female."}
  • {"criterion_text":"- Participant has a consistent caregiver who is ≥18 years of age at the Screening Visit. The caregiver needs to be able to complete the caregiver assessments defined for the entire study. Every attempt should be made to have the same evaluator complete the assessments for the duration of the study."}

Exclusion criteria

  • {"criterion_text":"- Participant has a history of lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years."}
  • {"criterion_text":"- Participant has clinically significant abnormality in vital signs according to the Investigator"}
  • {"criterion_text":"- Participant has an exclusionary cardiovascular or cardiopulmonary abnormality based on echocardiogram (ECHO), electrocardiogram (ECG), or physical examination, and is not approved for entry by the central cardiac reader. Exclusionary abnormalities include, but are not limited to: a. Greater than trace aortic valve regurgitation. b. Greater than mild mitral valve regurgitation. c. Possible signs of pulmonary arterial hypertension (PAH) with abnormal pulmonary artery systolic pressure (PASP) or PASP ≥35 mmHg. d. Evidence of left ventricular dysfunction (systolic or diastolic). e. Clinically significant structural cardiac abnormality, including but not limited to mitral valve prolapse, atrial or ventricular septal defects, or patent ductus arteriosus with reversal of shunt (right to left shunt). Note: Patent foramen ovale without a reversal of shunt or a bicuspid aortic valve is not considered exclusionary"}
  • {"criterion_text":"- Participant has a clinically significant medical condition, including chronic obstructive pulmonary disease, interstitial lung disease, portal hypertension, or need for invasive mechanical ventilation (eg, via tracheostomy), or has had clinically relevant symptoms or a clinically significant illness currently or in the 4 weeks prior to the Screening Visit that would negatively impact study participation, collection of study data, or pose a risk to the participant"}
  • {"criterion_text":"- Participant is taking >4 concomitant antiseizure medications (ASMs). Rescue medications are not included in the count"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Change from Baseline to Week 14 in Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score","definition_or_measurement_approach":"Change from baseline to Week 14 measured using the Rett Syndrome Behaviour Questionnaire (RSBQ) total score"}
  • {"endpoint_text":"- Clinical Global Impression of Change (CGIC) Score at Week 14","definition_or_measurement_approach":"Clinical Global Impression of Change (CGIC) score assessed at Week 14"}

Secondary endpoints

  • {"endpoint_text":"- Change from Baseline to Week 14 in Patient-Reported Outcomes Measurement Information System-Sleep Disturbance (PROMIS-SD) score","definition_or_measurement_approach":"Change from baseline to Week 14 measured by PROMIS-SD instrument"}
  • {"endpoint_text":"- Change from Baseline to Week 14 in Observer-Reported Communication Ability (ORCA) score","definition_or_measurement_approach":"Change from baseline to Week 14 measured by the Observer-Reported Communication Ability (ORCA) score"}
  • {"endpoint_text":"- Caregiver Global Impression of Change – Seizure (CaGIC-Seizure) score at Week 14","definition_or_measurement_approach":"Caregiver Global Impression of Change – Seizure (CaGIC-Seizure) assessed at Week 14"}
  • {"endpoint_text":"- Incidence of Treatment-emergent adverse event (TEAEs)","definition_or_measurement_approach":"Incidence (occurrence) of treatment-emergent adverse events recorded during the study"}
  • {"endpoint_text":"- Incidence of serious TEAEs","definition_or_measurement_approach":"Incidence (occurrence) of serious treatment-emergent adverse events recorded during the study"}
  • {"endpoint_text":"- Incidence of TEAEs leading to discontinuation","definition_or_measurement_approach":"Incidence of treatment-emergent adverse events that lead to study drug discontinuation"}
  • {"endpoint_text":"- Incidence of related TEAEs","definition_or_measurement_approach":"Incidence of treatment-emergent adverse events assessed as related to study drug"}
  • {"endpoint_text":"- Change from Baseline in QT interval corrected using Fridericia’s formula (QTcF) interval on 12-lead ECG at Week 14","definition_or_measurement_approach":"Change from baseline in QTcF measured on 12-lead ECG at Week 14 (Fridericia correction)"}
  • {"endpoint_text":"- Treatment-emergent Doppler Echocardiogram (ECHO) results meeting the Food and Drug Administration (FDA) case definition of drug-associated valvular heart disease (VHD)","definition_or_measurement_approach":"Doppler ECHO evaluations during treatment assessed against FDA case definition of drug-associated valvular heart disease"}
  • {"endpoint_text":"- Treatment-emergent Doppler ECHO results meeting the FDA case definition of pulmonary arterial hypertension (PAH) >35mmHg","definition_or_measurement_approach":"Doppler ECHO assessments during treatment meeting FDA case definition of PAH (PASP >35 mmHg)"}

Recruitment

Registry Or Advocacy Recruitment
True - Center For Information And Study On Clinical Research Participation Inc.
Digital Remote Recruitment
True - digital/remote methods include country-specific recruitment websites, digital awareness messages/images, website screening pages, and use of eCOA and Telehealth services (e.g. eCOA; Telehealth listed among third-party services).
Planned Sample Size
139
Recruitment Window Months
66
Consent Approach
Informed consent is provided by a legal representative on behalf of participants who are unable to provide consent themselves: "Participant has a legal representative capable of providing signed informed consent on behalf of the participant..." Age-specific participant information and ICFs are provided (documents listed for minors aged 5-11 and 12-17, parent/guardian versions, adult versions, and pregnancy-related ICFs). Materials are available in multiple country languages (examples in the document list: PL, ES, FR, IT, DE, HU, NL), and caregiver/assessor guidance is included; caregivers must be ≥18 and able to complete caregiver assessments.

Methods

  • HCP letters to healthcare professionals (e.g. 'K2_es-recruitment-hcp-letter' for Spain) targeting neurologists/paediatric neurologists
  • Study recruitment websites / website screening pages (country-specific recruitment websites are listed for ES, BE, FR, DE, IT, HU, PL) to reach patients and caregivers
  • Printed materials: recruitment flyers, brochures, posters distributed to patient/caregiver audiences at sites and events (country-specific versions present)
  • Digital awareness messages and images (social/digital channels) for patient/caregiver outreach (country-specific: awareness messages/images listed for ES, BE, FR, DE, IT, PL, HU)
  • Advocacy factsheets targeted to patient advocacy groups and caregivers (country-specific advocacy factsheets listed)
  • Recruitment procedure documents and legacy/legal notices for local implementation at sites (country-specific recruitment procedure documents listed)

Geography

Total Number Of Sites
29
Total Number Of Participants
82

Belgium

Earliest CTIS Part Ii Submission Date
29-03-2026
Latest Decision Or Authorization Date
15-04-2026
Processing Time Days
17
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Cliniques Universitaires Saint-Luc
Department Name
#11001:Pediatric Neurology
Contact Person Name
Marie-Cécile Nassogne
Site Name
Universitair Ziekenhuis Antwerpen
Department Name
#11002: Pediatric Neurology
Contact Person Name
An-Sofie Schoonjans
Contact Person Email
an-sofie.schoonjans@uza.be

France

Earliest CTIS Part Ii Submission Date
16-02-2026
Latest Decision Or Authorization Date
17-04-2026
Processing Time Days
60
Number Of Sites
5
Number Of Participants
12

Sites

Site Name
Centre Hospitalier Regional De Marseille
Department Name
#12004: Paediatric Neurology Department – Paediatric Epileptology
Contact Person Name
Mathieu Milh
Contact Person Email
Mathieu.milh@ap-hm.fr
Site Name
Centre Hospitalier Regional Et Universitaire De Brest
Department Name
#12005: Paediatric
Contact Person Name
Adélaïde Brosseau-Beauvir
Site Name
Assistance Publique Hopitaux De Paris
Department Name
#12001: Paediatric Neurology
Contact Person Name
Stéphane Auvin
Contact Person Email
Stephane.auvin@aphp.fr
Site Name
Hospital Femme Mere Enfant
Department Name
#12003: Neuropediatrics Department.
Contact Person Name
Vincent Des Portes
Contact Person Email
vincent.desportes@chu-lyon.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
#12006: Paediatric Neurology Department
Contact Person Name
Nadia Bahi-Buisson
Contact Person Email
Nadia.bahi-buisson@ap-hp.fr

Germany

Earliest CTIS Part Ii Submission Date
30-03-2026
Latest Decision Or Authorization Date
30-04-2026
Processing Time Days
31
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Schoen Klinik Vogtareuth SE & Co. KG
Department Name
#14001: Neuropädiatrie und Neurologische Rehabilitation Epilepsiezentrum für Kinder und Jugendliche
Contact Person Name
Milka Pringsheim
Contact Person Email
MPringsheim@schoen-klinik.de

Italy

Earliest CTIS Part Ii Submission Date
31-03-2026
Latest Decision Or Authorization Date
30-04-2026
Processing Time Days
30
Number Of Sites
9
Number Of Participants
30

Sites

Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
#17009: UOC Neuropsichiatria Infantile Largo Agostino Gemelli, 8 00168 Roma, Italy
Contact Person Name
Domenica Immacolata Battaglia
Site Name
Ospedale Pediatrico Bambino Gesu
Department Name
#17004: U.O.C Neurologia dell’epilessia e disturbi del movimento
Contact Person Name
Nicola Specchio
Contact Person Email
nicola.specchio@opbg.net
Site Name
ASST Fatebenefratelli Sacco
Department Name
#17001: Pediatric Neurology Unit – Department of Pediatrics
Contact Person Name
Enrico Alfei
Contact Person Email
enrico.alfei@asst-fbf-sacco.it
Site Name
Associazione Oasi Maria S.S.Onlus
Department Name
#17006: UOC di Neurologia e Neurofisiopatologia per l’età evolutiva
Contact Person Name
Maurizio Elia
Contact Person Email
melia@oasi.en.it
Site Name
Azienda Socio Sanitaria Territoriale Santi Paolo E Carlo
Department Name
#17005: Mental Health Department, Child Neuropsychiatry Unit and Epilepsy Center
Contact Person Name
Maria Canevini
Contact Person Email
mariapaola.canevini@unimi.it
Site Name
IRCCS Istituto Giannina Gaslini
Department Name
#17003: Child Neuropsychiatry Unit
Contact Person Name
Giulia Prato
Contact Person Email
giuliaprato@gaslini.org
Site Name
Azienda Ospedaliera Universitaria Meyer IRCCS
Department Name
#17007: Neurologia Pediatrica
Contact Person Name
Renzo Guerrini
Contact Person Email
renzo.guerrini@meyer.it
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
#17008: Neuropsichiatria Infantile
Contact Person Name
Gaetano Terrone
Contact Person Email
gaetano.terrone@unina.it
Site Name
IRCCS Fondazione Stella Maris
Department Name
#17002: Developmental Neurosciences
Contact Person Name
Emanuele Bartolini

Spain

Earliest CTIS Part Ii Submission Date
16-02-2026
Latest Decision Or Authorization Date
27-04-2026
Processing Time Days
70
Number Of Sites
7
Number Of Participants
16

Sites

Site Name
Futuremeds Spain S.L.
Contact Person Name
Marcos Madruga Garrido
Contact Person Email
Marcos.madruga@futuremeds.com
Site Name
IIS La Fe
Department Name
#11104: Neurology
Contact Person Name
Patricia Smeyers
Contact Person Email
patricia.smeyers@gmail.com
Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
#11101:Neurology
Contact Person Name
Rebeca Losada del Pozo
Contact Person Email
Rebeca_losada82@yahoo.es
Site Name
Hospital Sant Joan De Deu Barcelona
Department Name
#11107:Neurology
Contact Person Name
Maria del Mar O’Callaghan Gordo
Site Name
Hospital Universitari Vall D Hebron
Department Name
#11106: Neurology
Contact Person Name
Manuel Toledo Argany
Contact Person Email
manuel.toledo@vallhebron.cat
Site Name
Hospital Universitario Regional De Malaga
Department Name
#11103:Neurology
Contact Person Name
Pedro Serrano-Castro
Contact Person Email
p.serrano.eecc@gmail.com
Site Name
Hospital Infantil Universitario Nino Jesus
Department Name
#11105:Neurology
Contact Person Name
Elena Gonzalez Alguacil

Hungary

Earliest CTIS Part Ii Submission Date
24-03-2026
Latest Decision Or Authorization Date
27-04-2026
Processing Time Days
34
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Magyarorszagi Reformatus Egyhaz Bethesda Gyermekkorhaza
Department Name
#15001: Neurológia osztály
Contact Person Name
Andras Fogarasi
Contact Person Email
fog.andras@gmail.com
Site Name
University Of Debrecen
Department Name
#15002: Gyermekgyógyászati Klinika
Contact Person Name
Monika Bessenyei
Contact Person Email
besenyei.monika@med.unideb.hu

Poland

Earliest CTIS Part Ii Submission Date
08-04-2026
Latest Decision Or Authorization Date
23-04-2026
Processing Time Days
15
Number Of Sites
3
Number Of Participants
9

Sites

Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
#19003:Klinika Neurologii Rozwojowej
Contact Person Name
Maria Mazurkiewicz-Bełdzińska
Contact Person Email
agreements@uck.gda.pl
Site Name
Samodzielny Publiczny Zespol Zakladow Opieki Zdrowotnej W Pruszkowie
Department Name
#19001: Ambulatoryjna Opieka Specjalistyczna, Poradnia neurologii dziecięcej
Contact Person Name
Jolanta Strzelecka
Contact Person Email
jstrze@wp.pl
Site Name
Centrum Medyczne Plejady Magdalena Celinska Loewenhoff Michal Zolnowski sp.k.
Department Name
#19002: CENTRUM MEDYCZNE PLEJADY
Contact Person Name
Marta Żołnowska
Contact Person Email
trials@plejady.com.pl

Sponsor

Primary sponsor

Full Name
UCB Biosciences Inc.
Organisation Type
Laboratory/Research/Testing facility
Country Of Registered Address
United States

Contract research organisations

Name
Icon Clinical Research Limited
Responsibilities
Sponsor duties listed (codes present: 1,12,13,14,2,4,6) in source
Name
Bioclinica Inc.
Responsibilities
Imaging (ECHO Central Reader)
Name
4g Clinical LLC
Responsibilities
Sponsor duty code present (code 3) in source
Name
4G Clinical B.V.
Responsibilities
Sponsor duty code present (code 3) in source

Third parties

  • {"country":"United States","full_name":"Sitero LLC","duties_or_roles":"eConsent","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Kcas LLC","duties_or_roles":"PK sample analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Mural Health Technologies Inc.","duties_or_roles":"Patient Travel & Reimbursement Services","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"Scales & Linguistic validation services","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"eCOA; Telehealth; Cardiac safety (ECG Central Reader)","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Imaging (ECHO Central Reader)","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Center For Information And Study On Clinical Research Participation Inc.","duties_or_roles":"","organisation_type":"Patient organisation/association"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Fintepla 2.2 mg/ml oral solution
Active Substance
fenfluramine hydrochloride
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Authorisation Status
Authorised (marketing authorisation EU/1/20/1491/002)
Orphan Designation
Yes
Dose Levels
Maximum daily dose reported: 0.8 mg/kg
Maximum Dose
0.8 mg/kg per day
Investigational Product Name
Placebo matching < UCB PRODUCT (ZX008, fenfluramine hydrochloride oral solution) > and without active substance
Modality
Other

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