NIPH Clinical Trials Search

A Phase 3 study of fenfluramine hydrochloride in Rett syndrome

Basic Information

Recruitment status	Pending
Health condition(s) or Problem(s) studied	Rett Syndrome
Date of first enrollment	29/05/2026
Target sample size	16
Countries of recruitment	Australia,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,Chile,Japan,China,Japan,Colombia,Japan,France,Japan,Georgia,Japan,Germany,Japan,Hungary,Japan,Israel,Japan,Italy,Japan,Korea, Republic of,Japan,Mexico,Japan,Poland,Japan,Saudi Arabia,Japan,Spain,Japan,Switzerland,Japan,UAE,Japan,UK,Japan,USA,Japan
Study type	Interventional
Intervention(s)	Experimental: fenfluramine hydrochloride Participants will receive fenfluramine hydrochloride for 14 weeks in a double-blind period (including titration and maintenance), followed by a 2-week double-blind transition period. This is followed by a 52-week open-label treatment period. Participants may continue treatment until alternative access is available. Those who discontinue without continued access will undergo an 8-day taper and a 26-week follow-up. Placebo Comparator: Placebo Participants will receive a matching placebo for 14 weeks in a double-blind period (including titration and maintenance). After this period, they transition into a 2-week double-blind period with fenfluramine hydrochloride, followed by a 52-week open-label treatment period. Participants may continue treatment until alternative access is available. Those who discontinue without continued access will undergo an 8-day taper and a 26-week follow-up.

Outcome(s)

Primary Outcome

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

Secondary Outcome

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

Key inclusion & exclusion criteria

Age minimum	>= 5age old
Age maximum	<= 35age old
Gender	Both
Include criteria	-Participant has typical or classic Rett Syndrome (RTT) according to the RettSearch Consortium 2010 revised criteria -Participant has a documented disease-causing mutation in the methyl-CpG-binding protein 2 (MECP2) gene -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) -Participant has an Rett Syndrome Clinical Severity Scale (RTT-CSS) rating of 10 to 36 (inclusive) -Participant has a Clinical Global Impression-Severity (CGIS) score of >= 4 -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. -Participant is aged 5 to 35 years of age (inclusive) at the time of first administration of investigational intervention. -Male or female. -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.
Exclude criteria	-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. -Participant has clinically significant abnormality in vital signs according to the Investigator -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: 1. Greater than trace aortic valve regurgitation. 2. Greater than mild mitral valve regurgitation. 3. Possible signs of pulmonary arterial hypertension (PAH) with abnormal pulmonary artery systolic pressure (PASP) or PASP >= 35 mmHg. 4. Evidence of left ventricular dysfunction (systolic or diastolic). 5. 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. -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. -Participant is taking > 4 concomitant antiseizure medications (ASMs). Rescue medications are not included in the count.