A Phase 3 Study of Fenfluramine Hydrochloride in Rett Syndrome

NCT07503444 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: EP02472025-523157-34
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Rett Syndrome

Keywords

Fenfluramine HCl; RTT

Outcome Measures

Primary Outcomes (2)

• Change from Baseline to Week 14 in Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score

  The RSBQ is a caregiver-completed, instrument assessing behavioral and emotional features in RTT. The RSBQ consists of 45 items, including 8 subscales: General mood (8 items); Breathing problems (5 items); Hand behavior (6 items); Face movements (4 items); Body rocking and expressionless face (6 items); Nighttime behaviors (3 items); Fear/anxiety (4 items); and Walking/standing (2 items). Caregivers are asked to evaluate each RTT feature based on the current status of the patients on a 3-point scale as 0 ("not true"), 1 ("somewhat or sometimes true"), or 2 ("often true"), with the total score ranging from 0 to 90. Higher scores indicate increased disease severity. Seven items that do not belong under any of the subscales are classed as "uncategorized" but contribute to the overall total score.

  From Baseline (Day 1) to Week 14

• Clinical Global Impression of Change (CGIC) Score at Week 14

  The CGIC is a clinician-rated single item evaluating the degree of improvement or worsening of a participant's condition from Baseline following treatment or intervention. The CGIC uses a 7-point response scale, with the following ratings: "1: Very Much improved", "2: Much improved", "3: Minimally improved", "4: No change", "5: Minimally worse", "6: Much worse", "7: Very Much Worse".

  At Week 14

Secondary Outcomes (10)

• Change from Baseline to Week 14 in Patient-Reported Outcomes Measurement Information System-Sleep Disturbance (PROMIS-SD) score

  From Baseline (Day 1) to Week 14

• Change from Baseline to Week 14 in Observer-Reported Communication Ability (ORCA) score

  From Baseline (Day 1) to Week 14

• Caregiver Global Impression of Change - Seizure (CaGIC-Seizure) score at Week 14

  At Week 14

• Incidence of Treatment-emergent adverse event (TEAEs)

  From Baseline (Day 1) up to Week 98

• Incidence of serious TEAEs

  From Baseline (Day 1) up to Week 98

Study Arms (2)

fenfluramine hydrochloride

EXPERIMENTAL

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.

Drug: fenfluramine hydrochloride

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

fenfluramine hydrochloride DRUG

Oral solution

Also known as: Fintepla, ZX008

fenfluramine hydrochloride

Placebo OTHER

Oral solution

Placebo

Eligibility Criteria

• Age: 5 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Greater than trace aortic valve regurgitation.
• Greater than mild mitral valve regurgitation.
• Possible signs of pulmonary arterial hypertension (PAH) with abnormal pulmonary artery systolic pressure (PASP) or PASP ≥35 mmHg.
• Evidence of left ventricular dysfunction (systolic or diastolic).
• 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

Sponsors & Collaborators

• UCB BIOSCIENCES, Inc.: lead

Study Sites (2)

Ep0247 21010

Little Rock, Arkansas, 72202, United States

Location

Ep0247 21005

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Rett Syndrome

Interventions

Fenfluramine

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• UCB Cares

  0018445992273

  STUDY DIRECTOR

Central Study Contacts

UCB Cares

CONTACT

+18445992273; ucbcares@ucb.com

UCB Cares

CONTACT

0018445992273; UCBCares@ucb.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The study consists of a Double-Blind and an Open-Label (OL) Intervention Period. During OL Intervention Period, the sponsor, participants, caregivers, and Investigators will be unblinded to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2026
• First Posted: March 31, 2026
• Study Start (Estimated): May 31, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): November 15, 2030
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.

Locations

US (2)