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| ID | Type | Description | Link |
|---|---|---|---|
| 2025-523157-34 | Other Identifier | EU CTR |
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The purpose of this study is to investigate the efficacy of fenfluramine hydrochloride (HCl) versus placebo in study participants with Rett syndrome (RTT).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| fenfluramine hydrochloride | Drug | Oral solution |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline to Week 14 in Patient-Reported Outcomes Measurement Information System-Sleep Disturbance (PROMIS-SD) score | Sleep disturbances will be assessed by the PROMIS-SD parent proxy 8a version. Caregivers are asked to rate 8 items over the past 7 days on a 5-point scale: "1: Never", "2: Almost never", "3: Sometimes", "4: Almost always", and "5: Always", with higher scores indicating more severe sleep disturbances. |
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Inclusion Criteria:
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:
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
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| UCB Cares | Contact | +18445992273 | ucbcares@ucb.com | |
| UCB Cares | Contact | 0018445992273 | UCBCares@ucb.com |
| Name | Affiliation | Role |
|---|---|---|
| UCB Cares | 0018445992273 | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ep0247 21010 | Little Rock | Arkansas | 72202 | United States | ||
| Ep0247 21011 |
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. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, 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. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
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.
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.
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| ID | Term |
|---|---|
| D015518 | Rett Syndrome |
| ID | Term |
|---|---|
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
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| ID | Term |
|---|---|
| D005277 | Fenfluramine |
| ID | Term |
|---|---|
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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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.
| Placebo | Other | Oral solution |
|
| From Baseline (Day 1) to Week 14 |
| Change from Baseline to Week 14 in Observer-Reported Communication Ability (ORCA) score | The ORCA is an 84-item, observer-reported measure of communication ability over the past 30 days. The majority of the items included in the ORCA measure have 3 response options: "No or only once," "Sometimes," and "Yes, almost all the time", which enable derivation of an overall communication score and scores for each form of communication (expressive, receptive, and pragmatic), with higher scores indicating greater communication ability. | From Baseline (Day 1) to Week 14 |
| Caregiver Global Impression of Change - Seizure (CaGIC-Seizure) score at Week 14 | The CaGIC-Seizure is a caregiver-reported item assessing the change from Baseline in the participant's seizure status. The CaGIC-Seizure 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 |
| Incidence of Treatment-emergent adverse event (TEAEs) | An AE is any untoward medical occurrence in a clinical study participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment emergent adverse events (TEAEs) are adverse events that are not present prior to the pharmaceutical product administration or an already present event that worsens either in intensity or frequency. | From Baseline (Day 1) up to Week 98 |
| Incidence of serious TEAEs | An SAE is defined as any untoward medical occurrence that, at any dose, meets 1 or more of the criteria listed:
| From Baseline (Day 1) up to Week 98 |
| Incidence of TEAEs leading to discontinuation | An AE is any untoward medical occurrence in a clinical study participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment emergent adverse events (TEAEs) are adverse events that are not present prior to the pharmaceutical product administration or an already present event that worsens either in intensity or frequency. TEAEs leading to discontinuation will be reported. | From Baseline (Day 1) up to Week 98 |
| Incidence of related TEAEs | An AE is any untoward medical occurrence in a clinical study participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment emergent adverse events (TEAEs) are adverse events that are not present prior to the pharmaceutical product administration or an already present event that worsens either in intensity or frequency. Related TEAEs will be reported. | 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 | Change from Baseline in QTcF interval as measured by 12-lead ECG at Week 14 will be reported. | 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) | The FDA case definition of drug-associated VHD is aortic regurgitation ≥mild and/or mitral regurgitation ≥moderate with restricted valve motion, valve thickening, and/or physical signs or symptoms attributable to valve diseases. ECHO readings related to VHD on any of the 4 valves (aortic, mitral, pulmonary, tricuspid) will be reported with grades of absent, trace, mild, moderate, or severe. | From Baseline (Day 1) up to Week 98 |
| Treatment-emergent Doppler ECHO results meeting the FDA case definition of pulmonary arterial hypertension (PAH) >35mmHg | ECHO readings related to pulmonary arterial hypertension (PAH) on any of the 4 valves (aortic, mitral, pulmonary, tricuspid) will be reported with grades of absent, trace, mild, moderate, or severe. | From Baseline (Day 1) up to Week 98 |
| Orlando |
| Florida |
| 32806 |
| United States |
| Ep0247 21005 | Houston | Texas | 77030 | United States |
| Ep0247 21013 | Irving | Texas | 75062 | United States |
| Ep0247 15001 | Budapest | Hungary |
| Ep0247 15002 | Debrecen | Hungary |
| Ep0247 43006 | Musashimurayama-shi | Japan |
| Ep0247 43003 | Setagaya-ku | Japan |
| Ep0247 19002 | Krakow | Poland |
| Ep0247 11105 | Madrid | Spain |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020271 | Heredodegenerative Disorders, Nervous System |