This study is a two periods multi-center Phase II trial, with a 6 months double-blind, placebo-controlled period followed by open label period, to assess the efficacy and safety of alpelisib (BYL719) in pediatric and adult patients with Megalencephaly-CApillary malformation Polymicrogyria syndrome (MCAP)
Signed informed consent and assent (when applicable) from the patient, parent, or guardian must be obtained prior to any study related screening procedures are performed.
Male or female patients age ≥2 years and ≤40 years at the time of informed consent
Patients with diagnosis of MCAP* with neurodevelopmental disorder presentation (from specific learning disorder to severe intellectual disability)
Documented evidence of a postzygotic or constitutional mutation(s) in the PIK3CA gene performed in local laboratories using a Deoxyribonucleic acid (DNA) based validated test at the time of informed consent.
Patient previously treated with alpelisib
Known impairment of GI function due to concomitant disease that may significantly alter the absorption of the study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) at time of informed consent.
Participant with uncontrolled diabetes mellitus (Type I or II) at time of informed consent.
History of hypersensitivity to any drugs or metabolites of PI3K inhibitor or any of the excipients of alpelisib at time of informed consent.
Parallel
Alpelisib (BYL719)
DrugAdministration during open label and double-blind period of group B: alpelisib will be taken once a day each day over 24 mois During open label period of group A: alpelisib will be taken once a day each day over 24 months
Matching placebo
DrugDuring double-blind period of group A: matching placebo will be taken once a day each day over 6 months
Optional lumbar puncture + blood sample
Procedure/SurgeryBetween 6 and 24 months of treatment with Alpelisib
Proportion of participants with response at end of treatment assessed by the Vineland II Adaptive Behavior Scale (VABS-II)
Response defined by an improvement of at least 4 points in the Vineland II Adaptive Behavior Scale (VABS-II). The VABS-II consists of a form which will be filled during an interview with an adult who is familiar with the everyday activities of the patient (usually the parents). It is organized within a three-domain structure: communication, daily living skills, and socialization. In addition, VABS-II has a motor skills domain for the youngest children (younger than 6) and an optional maladaptive behavior index \[Sparrow et al.,2016\]. The domains (communication, daily living skills, and socialization) - standard scores have a mean of 100 and a standard deviation of 15. Adaptive levels can also be determined. A global standard score can also be computed (the Adaptive Behavior Composite standard score) and also has a mean of 100 and a standard deviation of 15.
Proportion of patients randomized with a response (yes/no) in group A and group B
Improvement of at least 4 points in the Vineland II Adaptive Behavior Scale (VABS-II) at 6 months of treatment in the group A compared to the group B
Changes from baseline in brain volume, vascularization, structural connectivity
Description of changes in brain volume, vascularization, structural connectivity, assessed by MRI
Frequency and severity of adverse events
Type, frequency, seriousness, and severity of adverse events per CTCAE v5.0 criteria
Proportion of participants with response at end of treatment
Improvement of at least 4 points in the Vineland II Adaptive Behavior Scale (VABS-II)
Click on the lead sponsor to view all of their trials.
Centre Hospitalier Universitaire Dijon
Lead sponsor
Novartis Pharmaceuticals
Collaborator
