- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT07503444
Fenfluramiinihydrokloridin vaiheen 3 tutkimus Rettin oireyhtymässä
Fenfluramiinin hydrokloridin tehon ja turvallisuuden arviointiin Retin oireyhtymää sairastavilla tutkimushenkilöillä suunniteltu vaiheen 3 satunnaistettu, kaksoissokko, lumekontrolloitu, rinnakkaisryhmä-, monikeskuksinen tutkimus avoimen jatko-osan kera
The purpose of this study is to investigate the efficacy of fenfluramine hydrochloride (HCl) versus placebo in study participants with Rett syndrome (RTT).
Tutkimuksen yleiskatsaus
Tila
Ehdot
Interventio / Hoito
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Vaihe
- Vaihe 3
Yhteystiedot ja paikat
Opiskeluyhteys
- Nimi: UCB Cares
- Puhelinnumero: 0018445992273
- Sähköposti: UCBCares@ucb.com
Tutki yhteystietojen varmuuskopiointi
- Nimi: UCB Cares
- Puhelinnumero: +18445992273
- Sähköposti: ucbcares@ucb.com
Opiskelupaikat
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Brussels, Belgia
- Rekrytointi
- Ep0247 11001
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Edegem, Belgia
- Rekrytointi
- Ep0247 11002
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Madrid, Espanja
- Rekrytointi
- Ep0247 11105
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Madrid, Espanja
- Rekrytointi
- Ep0247 11101
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Málaga, Espanja
- Rekrytointi
- Ep0247 11103
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Seville, Espanja
- Rekrytointi
- Ep0247 11102
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Tbilisi, Georgia
- Rekrytointi
- Ep0247 13001
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Tbilisi, Georgia
- Rekrytointi
- Ep0247 13002
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Ramat Gan, Israel
- Rekrytointi
- Ep0247 16001
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Genova, Italia
- Rekrytointi
- Ep0247 17003
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Milan, Italia
- Rekrytointi
- Ep0247 17001
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Naples, Italia
- Rekrytointi
- Ep0247 17008
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Pisa, Italia
- Rekrytointi
- Ep0247 17002
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Troina, Italia
- Rekrytointi
- Ep0247 17006
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Chiyoda-ku, Japani
- Rekrytointi
- Ep0247 43005
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Kodaira, Japani
- Rekrytointi
- Ep0247 43004
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Kurume, Japani
- Rekrytointi
- Ep0247 43001
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Musashimurayama-shi, Japani
- Rekrytointi
- Ep0247 43006
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Osaka, Japani
- Rekrytointi
- Ep0247 43002
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Setagaya-ku, Japani
- Rekrytointi
- Ep0247 43003
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Gdansk, Puola
- Rekrytointi
- Ep0247 19003
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Krakow, Puola
- Rekrytointi
- Ep0247 19002
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Brest, Ranska
- Rekrytointi
- Ep0247 12005
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Bron, Ranska
- Rekrytointi
- Ep0247 12003
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Marseille, Ranska
- Rekrytointi
- Ep0247 12004
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Paris, Ranska
- Rekrytointi
- Ep0247 12006
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Paris, Ranska
- Rekrytointi
- Ep0247 12001
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Vogtareuth, Saksa
- Rekrytointi
- Ep0247 14001
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Budapest, Unkari
- Rekrytointi
- Ep0247 15001
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Debrecen, Unkari
- Rekrytointi
- Ep0247 15002
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Manchester, Yhdistynyt kuningaskunta
- Rekrytointi
- Ep0247 11303
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Nottingham, Yhdistynyt kuningaskunta
- Rekrytointi
- Ep0247 11304
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Arkansas
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Little Rock, Arkansas, Yhdysvallat, 72202
- Rekrytointi
- Ep0247 21010
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Florida
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Miami, Florida, Yhdysvallat, 33155
- Rekrytointi
- Ep0247 21009
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Orlando, Florida, Yhdysvallat, 32806
- Rekrytointi
- Ep0247 21011
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Georgia
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Atlanta, Georgia, Yhdysvallat, 30322
- Rekrytointi
- Ep0247 21007
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Pennsylvania
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Philadelphia, Pennsylvania, Yhdysvallat, 19104-4318
- Rekrytointi
- Ep0247 21003
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Texas
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Houston, Texas, Yhdysvallat, 77030
- Rekrytointi
- Ep0247 21005
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Irving, Texas, Yhdysvallat, 75062
- Rekrytointi
- Ep0247 21013
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Washington
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Seattle, Washington, Yhdysvallat, 98105
- Rekrytointi
- Ep0247 21004
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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 or deletion 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:
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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.
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Participant has clinically significant abnormality in vital signs according to the Investigator
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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
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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
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Participant is taking >4 concomitant antiseizure medications (ASMs). Rescue medications are not included in the count
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Kolminkertaistaa
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: 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. |
Oral solution
Muut nimet:
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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. |
Oral solution |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Change from Baseline to Week 14 in Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score
Aikaikkuna: From Baseline (Day 1) to Week 14
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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
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Clinical Global Impression of Change (CGIC) Score at Week 14
Aikaikkuna: At Week 14
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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
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Change from Baseline to Week 14 in Patient-Reported Outcomes Measurement Information System-Sleep Disturbance (PROMIS-SD) score
Aikaikkuna: From Baseline (Day 1) to Week 14
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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. |
From Baseline (Day 1) to Week 14
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Change from Baseline to Week 14 in Observer-Reported Communication Ability (ORCA) score
Aikaikkuna: From Baseline (Day 1) to Week 14
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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
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Caregiver Global Impression of Change - Seizure (CaGIC-Seizure) score at Week 14
Aikaikkuna: At Week 14
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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
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Incidence of treatment-emergent adverse events (TEAEs) during the double-blind intervention period
Aikaikkuna: From Baseline (Day 1) up to Week 14
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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 14
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Incidence of serious TEAEs during the double-blind intervention period
Aikaikkuna: From Baseline (Day 1) up to Week 14
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An SAE is defined as any untoward medical occurrence that, at any dose, meets 1 or more of the criteria listed:
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From Baseline (Day 1) up to Week 14
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Incidence of TEAEs leading to discontinuation during the double-blind intervention period
Aikaikkuna: From Baseline (Day 1) up to Week 14
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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 14
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Incidence of related TEAEs during the double-blind intervention period
Aikaikkuna: From Baseline (Day 1) up to Week 14
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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 14
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Change from Baseline in QT interval corrected using Fridericia's formula (QTcF) interval on 12-lead ECG by visit during the double-blind intervention period
Aikaikkuna: From Baseline (Day 1) up to Week 14
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Change from Baseline in QTcF interval as measured by 12-lead ECG up to Week 14 by visit will be reported |
From Baseline (Day 1) up to Week 14
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Incidence of treatment-emergent Doppler Echocardiogram (ECHO) results meeting the Food and Drug Administration (FDA) case definition of drug-associated valvular heart disease (VHD) during the double-blind intervention period
Aikaikkuna: From Baseline (Day 1) up to Week 14
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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 14
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Incidence of treatment-emergent Doppler ECHO results meeting the FDA case definition of PAH (defined as a PASP >35mmHg) during the double-blind intervention period
Aikaikkuna: From Baseline (Day 1) up to Week 14
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ECHO readings related to pulmonary arterial hypertenstion (PAH) will be reported based on Pulmonary artery systolic pressure (PASP). |
From Baseline (Day 1) up to Week 14
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Incidence of treatment-emergent adverse events (TEAEs) from baseline to end of safety follow up
Aikaikkuna: From Baseline (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
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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 (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
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Incidence of serious TEAEs from baseline to end of safety follow up
Aikaikkuna: From Baseline (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
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An SAE is defined as any untoward medical occurrence that, at any dose, meets 1 or more of the criteria listed:
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From Baseline (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
|
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Incidence of TEAEs leading to discontinuation from baseline to end of safety follow up
Aikaikkuna: From Baseline (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
|
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 (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
|
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Incidence of related TEAEs from baseline to end of safety follow up
Aikaikkuna: From Baseline (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
|
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 (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
|
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Change from Baseline in QT interval corrected using Fridericia's formula (QTcF) interval on 12-lead ECG by visit from baseline to end of safety follow up
Aikaikkuna: From Baseline (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
|
Change from Baseline in QTcF interval as measured by 12-lead ECG up to Week 98 by visit will be reported |
From Baseline (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
|
|
Incidence of treatment-emergent Doppler Echocardiogram (ECHO) results meeting the Food and Drug Administration (FDA) case definition of drug-associated valvular heart disease (VHD) from baseline to end of safety follow up
Aikaikkuna: From Baseline (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
|
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 (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
|
|
Incidence of treatment-emergent Doppler ECHO results meeting the FDA case definition of PAH (defined as a PASP >35mmHg) from baseline to end of safety follow up
Aikaikkuna: From Baseline (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
|
ECHO readings related to pulmonary arterial hypertenstion (PAH) will be reported based on Pulmonary artery systolic pressure (PASP). |
From Baseline (Day1) to the End of Safety Follow Up (up to 3 years and 10 months)
|
Yhteistyökumppanit ja tutkijat
Sponsori
Tutkijat
- Opintojohtaja: UCB Cares, 0018445992273
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Neurologiset ilmenemismuodot
- Hermoston sairaudet
- Geneettiset sairaudet, synnynnäiset
- Neurokäyttäytymisoireet
- Heredodegeneratiiviset häiriöt, hermosto
- Henkinen vamma
- Geneettiset sairaudet, X-Linked
- Synnynnäiset, perinnölliset ja vastasyntyneiden sairaudet ja poikkeavuudet
- X-Linked Intellectual Disability
- Rettin syndrooma
- Orgaaniset kemikaalit
- Amiini
- Fenetyyliamiinit
- Etyyliamiinit
- Fenfluramiini
Muut tutkimustunnusnumerot
- EP0247
- 2025-523157-34 (Muu tunniste: EU CTR)
- 2025 (Yhdysvaltain NIH-apuraha/sopimus)
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
IPD-suunnitelman kuvaus
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.
IPD-jaon aikakehys
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.
IPD-jaon käyttöoikeuskriteerit
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.
IPD-jakamista tukeva tietotyyppi
- STUDY_PROTOCOL
- MAHLA
- CSR
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta
Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
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