BMJ open · 2024
A phase II double-blind multicentre, placebo-controlled trial to assess the efficacy and safety of alpelisib (BYL719) in paediatric and adult patients with Megalencephaly-CApillary malformation Polymicrogyria syndrome (MCAP): the SESAM study protocol.
СтатьяПротокол клинического исследованияНазвание и аннотация: Перевод в очереди
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Luu Maxime, Vabres Pierre, Espitalier Aurélie, Maurer Agnès, Garde Aurore, Racine Caroline, Carpentier Maud, Rega Adélaide, Loffroy Romaric, Hadouiri Nawale, Boddaert Nathalie, Curie Aurore, Guibaud Laurent, Chebbi Mouna, Charligny Julie, Kuentz Paul, Canaud Guillaume, Bahi-Buisson Nadia, Fleck Camille, Cransac Amelie, Bardou Marc, Faivre Laurence, SESAM study group
Аннотация
INTRODUCTION: The megalencephaly capillary malformation polymicrogyria (MCAP syndrome) results from mosaic gain-of-function PIK3CA variants. The main clinical features are macrocephaly, somatic overgrowth, neurodevelopmental delay and brain anomalies. Alpelisib (Vijoice) is a recently FDA-approved PI3Kα-specific inhibitor for patients with PIK3CA-related overgrowth spectrum (PROS). During its development, in patients with the MCAP subgroup of PROS, there was no specific, standardised evaluation of the effect on neuro-cognitive functioning. Moreover, it remains unknown if the molecule crosses the blood-brain barrier. Our objective is to evaluate the efficacy of a 24 month treatment with alpelisib on adaptive behaviour in patients with MCAP syndrome.
METHODS AND ANALYSIS: SESAM is an industry-sponsored two-period multicentre French academic phase II trial, with a 6-month double-blind, placebo-controlled period followed by an open-label period. The primary endpoint is a ≥4-point improvement in the Vineland II Adaptive Behaviour Scale (VABS), 24 months after treatment initiation. Secondary objectives are safety, VABS improvement at 6 months, impact on the quality of life, epilepsy and hypotonia. 20 patients aged 2 to 40 years with an MCAP diagnosis and neurodevelopmental disorders of various degrees, will be followed monthly in local centres, centrally assessed (clinical, biological, neuropsychological and functional evaluation) at baseline and every 6 months. Patients will be evaluated by volumetric MRI at baseline and at 24 months. An optional lumbar puncture will be performed to investigate blood-brain barrier crossing. Inclusions were completed by April 2024, with the end of follow-up in November 2026.Given the efficacy of alpelisib in patients with PROS, if the drug crosses the blood-brain barrier, we can expect a clinical benefit for patients with neurocognitive disorders.
ETHICS AND DISSEMINATION: Ethical approval was given by CPP Sud-Ouest et Outre-Mer I (reference: 2022-500197-34-01). Findings from this study will be disseminated via publication, reports and conference presentations.
TRIAL REGISTRATION NUMBER: NCT05577754.
METHODS AND ANALYSIS: SESAM is an industry-sponsored two-period multicentre French academic phase II trial, with a 6-month double-blind, placebo-controlled period followed by an open-label period. The primary endpoint is a ≥4-point improvement in the Vineland II Adaptive Behaviour Scale (VABS), 24 months after treatment initiation. Secondary objectives are safety, VABS improvement at 6 months, impact on the quality of life, epilepsy and hypotonia. 20 patients aged 2 to 40 years with an MCAP diagnosis and neurodevelopmental disorders of various degrees, will be followed monthly in local centres, centrally assessed (clinical, biological, neuropsychological and functional evaluation) at baseline and every 6 months. Patients will be evaluated by volumetric MRI at baseline and at 24 months. An optional lumbar puncture will be performed to investigate blood-brain barrier crossing. Inclusions were completed by April 2024, with the end of follow-up in November 2026.Given the efficacy of alpelisib in patients with PROS, if the drug crosses the blood-brain barrier, we can expect a clinical benefit for patients with neurocognitive disorders.
ETHICS AND DISSEMINATION: Ethical approval was given by CPP Sud-Ouest et Outre-Mer I (reference: 2022-500197-34-01). Findings from this study will be disseminated via publication, reports and conference presentations.
TRIAL REGISTRATION NUMBER: NCT05577754.
Предметные рубрики MeSH
AdolescentAdultChildChild, PreschoolFemaleHumansMaleYoung AdultCapillariesCentral Nervous System Vascular MalformationsClinical Trials, Phase II as TopicDouble-Blind MethodMegalencephalyMulticenter Studies as TopicPolymicrogyriaTreatment OutcomeRandomized Controlled Trials as TopicThiazolesVascular Malformations