A Phase 3 Study of Fenfluramine Hydrochloride in Rett Syndrome

Официальное название

A Phase 3 Randomized, Double-Blind, Placebo Controlled, Parallel Group, Multicenter Study With Open-Label Extension to Evaluate the Efficacy And Safety of Fenfluramine Hydrochloride in Study Participants With Rett Syndrome

Обзор

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

Вмешательства

• Препарат fenfluramine hydrochloride
  Oral solution
• Другое Placebo
  Oral solution

Первичные конечные точки

• Change from Baseline to Week 14 in Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score [Срок оценки: From Baseline (Day 1) to Week 14]
• Clinical Global Impression of Change (CGIC) Score at Week 14 [Срок оценки: At Week 14]

Вторичные конечные точки (10)

• Change from Baseline to Week 14 in Patient-Reported Outcomes Measurement Information System-Sleep Disturbance (PROMIS-SD) score [Срок оценки: From Baseline (Day 1) to Week 14]
• Change from Baseline to Week 14 in Observer-Reported Communication Ability (ORCA) score [Срок оценки: From Baseline (Day 1) to Week 14]
• Caregiver Global Impression of Change - Seizure (CaGIC-Seizure) score at Week 14 [Срок оценки: At Week 14]
• Incidence of Treatment-emergent adverse event (TEAEs) [Срок оценки: From Baseline (Day 1) up to Week 98]
• Incidence of serious TEAEs [Срок оценки: From Baseline (Day 1) up to Week 98]
• Incidence of TEAEs leading to discontinuation [Срок оценки: From Baseline (Day 1) up to Week 98]
• Incidence of related TEAEs [Срок оценки: From Baseline (Day 1) up to Week 98]
• Change from Baseline in QT interval corrected using Fridericia's formula (QTcF) interval on 12-lead ECG at Week 14 [Срок оценки: 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) [Срок оценки: From Baseline (Day 1) up to Week 98]
• Treatment-emergent Doppler ECHO results meeting the FDA case definition of pulmonary arterial hypertension (PAH) >35mmHg [Срок оценки: From Baseline (Day 1) up to Week 98]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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:

• 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).
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 4 центра

• Ep0247 21010 — Little Rock
• Ep0247 21011 — Orlando
• Ep0247 21005 — Houston
• Ep0247 21013 — Irving

Венгрия · 2 центра

• Ep0247 15001 — Budapest
• Ep0247 15002 — Debrecen

Япония · 2 центра

• Ep0247 43006 — Musashimurayama-shi
• Ep0247 43003 — Setagaya-ku

Польша · 1 центр

• Ep0247 19002 — Krakow

Испания · 1 центр

• Ep0247 11105 — Madrid

Идентификаторы

NCT: NCT07503444 · EP0247 · 2025-523157-34

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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