A Phase 3 Study of Fenfluramine Hydrochloride in Rett Syndrome

UCB

Status and phase: Not yet enrolling; Phase 3

Conditions: Rett Syndrome

Treatments: Other: Placebo; Drug: fenfluramine hydrochloride

Study type: Interventional

Funder types: Industry

Identifiers

NCT07503444

2025-523157-34 (Other Identifier)

EP0247

Details and patient eligibility

About

The purpose of this study is to investigate the efficacy of fenfluramine hydrochloride (HCl) versus placebo in study participants with Rett syndrome (RTT).

Enrollment: 200 estimated patients

Sex: All

Ages: 5 to 35 years old

Volunteers: No Healthy Volunteers

Inclusion 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.

Exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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200 participants in 2 patient groups, including a placebo group

fenfluramine hydrochloride

Experimental group

Description:

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.

Treatment:

Drug: fenfluramine hydrochloride

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Other: Placebo