Assessment of the Efficacy and Safety of Alpelisib (BYL719) in Pediatric and Adult Patients With Megalencephaly-CApillary Malformation Polymicrogyria Syndrome (MCAP)
NCT ID: NCT05577754
Last Updated: 2025-12-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
20 participants
INTERVENTIONAL
2022-11-28
2027-03-31
Brief Summary
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Detailed Description
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Eligible patients will be randomized in a 1:1 ratio for the first period (alpelisib or placebo). A first assessment will be performed at 6 months. Patients completing this first period will enter the open label period, and either start alpelisib if they were on placebo, continue at the same dose if responders, or increase dose if not responders (dose increase only possible for children of 5 years old and over), and if no unacceptable toxicity occurs.
Patients will be followed monthly in local centres, and 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.
Participant may be discontinued from treatment with alpelisib earlier due to unacceptable toxicity, confirmed disease progression, death, and/or any other reason at the discretion of the investigator or the participant.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Group A
Alpelisib (BYL719)
Administration 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
During double-blind period of group A: matching placebo will be taken once a day each day over 6 months
Optional lumbar puncture + blood sample
Between 6 and 24 months of treatment with Alpelisib
Group B
Alpelisib (BYL719)
Administration 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
Optional lumbar puncture + blood sample
Between 6 and 24 months of treatment with Alpelisib
Interventions
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Alpelisib (BYL719)
Administration 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
During double-blind period of group A: matching placebo will be taken once a day each day over 6 months
Optional lumbar puncture + blood sample
Between 6 and 24 months of treatment with Alpelisib
Eligibility Criteria
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Inclusion Criteria
2. Male or female patients age ≥2 years and ≤40 years at the time of informed consent
3. Patients with diagnosis of MCAP\* with neurodevelopmental disorder presentation (from specific learning disorder to severe intellectual disability)
4. 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.
5. Adequate bone marrow and organ function (assessed during the screening visit):
1. Absolute neutrophil count ≥ 1.5 × 109/L
2. Platelets ≥ 100 × 109/L
3. Hemoglobin ≥ 9.0 g/dL (transfusions are allowed)
4. 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
5. Potassium within normal limits.
6. INR ≤1.5
7. Creatinine Clearance ≥ 30 mL/min using Modification of Diet in Renal Disease
8. (MDRD) (≥18 years old) or creatinine-based Bedside Schwartz (˂18 years old) Glomerular filtration rate (GFR) equation
9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
10. 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
11. Fasting plasma glucose (FPG) ≤ 140 mg/dL (7.7 mmol/L) and Glycosylated hemoglobin (HbA1c) ≤ 6.5% (both criteria have to be met)
12. Fasting Serum lipase ≤ ULN
6. Able to swallow study drug according to age: tablets, or as drinkable suspension, or granules (under development)
7. For women of child-bearing potential only: negative pregnancy test at screening visit
8. 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.
7\. For exploratory study only : signed informed optional consent for lumbar puncture
Exclusion Criteria
1. Patient previously treated with alpelisib
2. 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.
3. Participant with uncontrolled diabetes mellitus (Type I or II) at time of informed consent.
4. History of hypersensitivity to any drugs or metabolites of PI3K inhibitor or any of the excipients of alpelisib at time of informed consent.
5. Participant with other concurrent severe and/or uncontrolled medical conditions that would, in the treating Physician's judgment, contraindicate administration of alpelisib (e.g., active and/or uncontrolled severe infection, chronic active hepatitis, hepatic impairment Child Pugh score C, immuno-compromised, etc.) at time of informed consent.
6. Female participants of childbearing potential and male participants who do not agree at time of informed consent to abstinence or, if sexually active, unwilling to use a condom and/or a highly effective method of contraception for the duration of the study and for one week following discontinuation of alpelisib. Highly effective contraception methods is one of the following:
1. Total abstinence: when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
2. Female sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks before taking alpelisib. In case of oophorectomy alone, only when the reproductive status of the female has been confirmed by follow-up hormone level assessment
3. Male sterilization at least 6 months prior to screening. The vasectomized male partner should be the sole partner for that study participant
4. Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF.
7. Treatment by any mTOR or PI3K-AKT signaling pathway inhibitor within 1 month before inclusion
8. History of prior and or ongoing malignancy (within 5 years before informed consent except radically treated Carcinoma in situ of radically treated basal-cell carcinoma of skin or thyroid gland well differentiated microcarcinoma or Stage 1 Wilms' tumor of a histology other than anaplastic), or ongoing investigations or treatment for malignancy at time of informed consent.
9. Treatment with strong inducers of CYP3A4 and inhibitors of Breast Cancer Resistance Protein (BCRP) that cannot be stopped at least the week prior to the screening
10. Debulking or other major surgery performed within 3 months at time of informed consent
11. Known history of Steven Johnson's syndrome, erythema multiform or toxic epidermal necrolysis at time of informed consent.
12. For participants ≥ 6 years of age: Participants with documented pneumonitis or interstitial lung disease at the time of informed consent and with impaired lung function (e.g., FEV1 (Forced expiratory volume) or DLCO (Diffusing Capacity of the Lung for Carbon Monoxide) ≤ 70% of predicted) that is not related to PROS.
13. For participants between 2 to 5 years of age: Participants with documented or suspicious pneumonitis or interstitial lung disease based on MRI images at time of informed consent.
14. History of acute pancreatitis within 1 year before informed consent or past medical history of chronic pancreatitis at time of informed consent.
15. Clinically significant heart disease at time of informed consent, including:
1. History of documented congestive heart failure (New York Heart Association functional classification III-IV)
2. Clinically significant uncontrolled cardiac arrhythmias
3. Long QT syndrome, family history of idiopathic sudden death or congenital long QTsyndrome
4. Corrected QT (QTcF) at screening: \>470 ms for ≥18 years old / \>450 ms for \<18 years old
5. Creatinine clearance \< 70ml/min/1.73 m²
16. Patient currently, or in the 3 months before inclusion, enrolled in another interventional trial.
17. Person not affiliated to a national health insurance scheme
18. Patient, parents or legal authorized reprensentative incapable of expressing consent
19. Inability to attend all trial visits
20. For the optional consent only : contra indication to lumbar puncture:
1. Known intracranial hypertension
2. infection at puncture site
3. known coagulation disorders
4. Platelets \< 50 × 109/L
2 Years
40 Years
ALL
No
Sponsors
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Novartis Pharmaceuticals
INDUSTRY
Centre Hospitalier Universitaire Dijon
OTHER
Responsible Party
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Locations
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CHU Amiens
Amiens, , France
CHU d'Angers
Angers, , France
CHRU Brest
Brest, , France
HCL - Groupement Hospitalier Est Hôpital Femme-Mère-Enfant
Bron, , France
Chu Estaing
Clermont-Ferrand, , France
Chu Dijon Bourgogne
Dijon, , France
CHU Dijon Bourgogne - CIC-P
Dijon, , France
CHU de Lille
Lille, , France
CHRU Nîmes
Nîmes, , France
AP-HP Hôpital Necker-Enfants Malades - CIC
Paris, , France
AP-HP Hôpital Necker-Enfants Malades
Paris, , France
CHU Rennes
Rennes, , France
CHRU Tours
Tours, , France
Countries
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Central Contacts
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Facility Contacts
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Bénédicte DEMEER
Role: primary
Dominique BONNEAU
Role: primary
Adélaïde BROSSEAU-BEAUVIR
Role: primary
Laurent GUIBAUD
Role: primary
Florian CHERIK
Role: primary
Laurence OLIVIER-FAIVRE
Role: primary
Florence PETIT
Role: primary
Camille CENNI
Role: primary
Guillaume CANAUD
Role: primary
Alinoë LAVILLAUREIX
Role: primary
Annabel MARUANI
Role: primary
References
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Sparrow SSC, D.V.; Saulnier, C.A. Vineland-3: Vineland Adaptive Behavior Scales. 3rd ed. Pearson Assessments; Minneapolis, MN, USA. 2016.
Curie A, Brun A, Cheylus A, Reboul A, Nazir T, Bussy G, Delange K, Paulignan Y, Mercier S, David A, Marignier S, Merle L, de Freminville B, Prieur F, Till M, Mortemousque I, Toutain A, Bieth E, Touraine R, Sanlaville D, Chelly J, Kong J, Ott D, Kassai B, Hadjikhani N, Gollub RL, des Portes V. A Novel Analog Reasoning Paradigm: New Insights in Intellectually Disabled Patients. PLoS One. 2016 Feb 26;11(2):e0149717. doi: 10.1371/journal.pone.0149717. eCollection 2016.
Luu M, Vabres P, Espitalier A, Maurer A, Garde A, Racine C, Carpentier M, Rega A, Loffroy R, Hadouiri N, Boddaert N, Curie A, Guibaud L, Chebbi M, Charligny J, Kuentz P, Canaud G, Bahi-Buisson N, Fleck C, Cransac A, Bardou M, Faivre L; SESAM study group. 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. BMJ Open. 2024 Dec 20;14(12):e084614. doi: 10.1136/bmjopen-2024-084614.
Related Links
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Related Info
Other Identifiers
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OLIVIER FAIVRE Novartis 2021
Identifier Type: -
Identifier Source: org_study_id