A Phase II Double-blind Multi-center, Placebo-controlled Trial, to Assess the Efficacy and Safety of Alpelisib (BYL719) in Pediatric and Adult Patients With Megalencephaly-CApillary Malformation Polymicrogyria Syndrome (MCAP)
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.
• Adequate bone marrow and organ function (assessed during the screening visit):
‣ Absolute neutrophil count ≥ 1.5 × 109/L
⁃ Platelets ≥ 100 × 109/L
⁃ Hemoglobin ≥ 9.0 g/dL (transfusions are allowed)
⁃ Calcium (corrected for serum albumin) and magnesium within normal limits or ≤Grade 1 according to NCI-CTCAE version 5.0 if judged clinically not significant by the investigator
⁃ Potassium within normal limits.
⁃ INR ≤1.5
⁃ Creatinine Clearance ≥ 30 mL/min using Modification of Diet in Renal Disease
⁃ (MDRD) (≥18 years old) or creatinine-based Bedside Schwartz (˂18 years old) Glomerular filtration rate (GFR) equation
⁃ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
‣ Total bilirubin\< ULN except for patients with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN
‣ Fasting plasma glucose (FPG) ≤ 140 mg/dL (7.7 mmol/L) and Glycosylated hemoglobin (HbA1c) ≤ 6.5% (both criteria have to be met)
‣ Fasting Serum lipase ≤ ULN
• Able to swallow study drug according to age: tablets, or as drinkable suspension, or granules (under development)
• For women of child-bearing potential only: negative pregnancy test at screening visit
• Male patients with sexual partners who are pregnant, possibly pregnant or who could become pregnant should use condoms during sexual intercourse for the duration of the study and for one week following discontinuation of alpelisib.
• For exploratory study only : signed informed optional consent for lumbar puncture