A study to learn if fenfluramine hydrochloride is safe and works in people with Rett syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UCB Biosciences Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Decision date (initial)

2026-04-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

UCB Biosciences Inc., 4000 Paramount Parkway, Suite 200, Morrisville, NC USA, 27560

External identifiers

EU CT number

2025-523157-34-00

WHO UTN

U1111-1326-9925

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others

To investigate the efficacy of fenfluramine HCl versus placebo in study participants with Rett syndrome (RTT)

Secondary objectives 4

1. To investigate the efficacy of fenfluramine HCl versus placebo on sleep in study participants with Rett syndrome (RTT).
2. To investigate the efficacy of fenfluramine HCl versus placebo on the ability to communicate in study participants with RTT.
3. To investigate the efficacy of fenfluramine HCl versus placebo on seizures in study participants with RTT and seizures.
4. To investigate the safety and tolerability of fenfluramine HCl versus placebo in study participants with RTT.

Conditions and MedDRA coding

Rett syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participant has typical or classic Rett Syndrome (RTT) according to the RettSearch Consortium 2010 revised criteria
2. Participant has a documented disease-causing mutation in the methyl-CpG-binding protein 2 (MECP2) gene
3. 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)
4. Participant has an Rett Syndrome Clinical Severity Scale (RTT-CSS) rating of 10 to 36 (inclusive)
5. Participant has a Clinical Global Impression-Severity (CGIS) score of ≥4
6. 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.
7. Participant is aged 5 to 35 years of age (inclusive) at the time of first administration of investigational intervention.
8. Male or female.
9. 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 5

1. 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.
2. Participant has clinically significant abnormality in vital signs according to the Investigator
3. 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
4. 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
5. Participant is taking >4 concomitant antiseizure medications (ASMs). Rescue medications are not included in the count

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change from Baseline to Week 14 in Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score
2. Clinical Global Impression of Change (CGIC) Score at Week 14

Secondary endpoints 10

1. Change from Baseline to Week 14 in Patient-Reported Outcomes Measurement Information System-Sleep Disturbance (PROMIS-SD) score
2. Change from Baseline to Week 14 in Observer-Reported Communication Ability (ORCA) score
3. Caregiver Global Impression of Change – Seizure (CaGIC-Seizure) score at Week 14
4. Incidence of Treatment-emergent adverse event (TEAEs)
5. Incidence of serious TEAEs
6. Incidence of TEAEs leading to discontinuation
7. Incidence of related TEAEs
8. Change from Baseline in QT interval corrected using Fridericia’s formula (QTcF) interval on 12-lead ECG at Week 14
9. Treatment-emergent Doppler Echocardiogram (ECHO) results meeting the Food and Drug Administration (FDA) case definition of drug-associated valvular heart disease (VHD)
10. Treatment-emergent Doppler ECHO results meeting the FDA case definition of pulmonary arterial hypertension (PAH) >35mmHg

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UCB Biosciences Inc.

Sponsor organisation

UCB Biosciences Inc.

Address

4000 Paramount Parkway Suite 200

City

Morrisville

Postcode

27560-8484

Country

United States

Scientific contact point

Organisation

UCB Biosciences Inc.

Contact name

UCB Cares

Public contact point

Organisation

UCB Biosciences Inc.

Contact name

UCB Cares

Third parties 10

Locations

7 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 168 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications