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Megalencephaly-capillary Malformation Polymicrogyria Syndrome (MCAP)Phase 2SESAMNCT05577754

Assessment of the Efficacy and Safety of Alpelisib (BYL719) in Pediatric and Adult Patients With Megalencephaly-CApillary Malformation Polymicrogyria Syndrome (MCAP)

A Phase 2 study testing Alpelisib (BYL719) and Optional lumbar puncture + blood sample in people with Megalencephaly-capillary Malformation Polymicrogyria Syndrome (MCAP), run by Centre Hospitalier Universitaire Dijon at 13 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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) Read more about this study

Who is it for?
Ages 2 to 40 years
What is being tested?
Alpelisib (BYL719) and Optional lumbar puncture + blood sample
Type of treatment
Surgery or procedure
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
13 sitesFrance
Study dates
28 Nov 2022to Mar 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 40 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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.
  • 7. For exploratory study only : signed informed optional consent for lumbar puncture

Who cannot join

  • Participants meeting any of the following criteria are not eligible for inclusion in this study:
  • 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.
  • 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.
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  • 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:
  • 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
  • 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
  • Male sterilization at least 6 months prior to screening. The vasectomized male partner should be the sole partner for that study participant
  • 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.
  • Treatment by any mTOR or PI3K-AKT signaling pathway inhibitor within 1 month before inclusion
  • 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.
  • 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
  • Debulking or other major surgery performed within 3 months at time of informed consent
  • Known history of Steven Johnson's syndrome, erythema multiform or toxic epidermal necrolysis at time of informed consent.
  • 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.
  • 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.
  • History of acute pancreatitis within 1 year before informed consent or past medical history of chronic pancreatitis at time of informed consent.
  • Clinically significant heart disease at time of informed consent, including:
  • History of documented congestive heart failure (New York Heart Association functional classification III-IV)
  • Clinically significant uncontrolled cardiac arrhythmias
  • Long QT syndrome, family history of idiopathic sudden death or congenital long QTsyndrome
  • Corrected QT (QTcF) at screening: \>470 ms for ≥18 years old / \>450 ms for \<18 years old
  • Creatinine clearance \< 70ml/min/1.73 m²
  • Patient currently, or in the 3 months before inclusion, enrolled in another interventional trial.
  • Person not affiliated to a national health insurance scheme
  • Patient, parents or legal authorized reprensentative incapable of expressing consent
  • Inability to attend all trial visits
  • For the optional consent only : contra indication to lumbar puncture:
  • Known intracranial hypertension
  • infection at puncture site
  • known coagulation disorders
  • Platelets \< 50 × 109/L

Trial locations and contacts

13 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Laurence OLIVIER-FAIVRE contact

0380295313

laurence.faivre@chu-dijon.fr

13 sites in 1 country

France13 sites, 11 recruiting

  • CHU Amiens

    Amiens, 80054 Amiens

    Bénédicte DEMEER, 03 22 08 75 81, demeer.benedicte@chu-amiens.fr

    Recruiting

  • CHU d'Angers

    Angers, 49933

    Dominique BONNEAU, 02 41 35 38 83, dobonneau@chu-angers.fr

    Recruiting

  • CHRU Brest

    Brest, 29200

    Adélaïde BROSSEAU-BEAUVIR, 0298223657, adelaide.brosseau-beauvir@chu-brest.fr

    Not yet recruiting

  • HCL - Groupement Hospitalier Est Hôpital Femme-Mère-Enfant

    Bron, 69677

    Laurent GUIBAUD, 04 27 55 54 11, laurent.guibaud@chu-lyon.fr

    Recruiting

  • Chu Estaing

    Clermont-Ferrand, 63003

    Florian CHERIK, 04 73 75 06 54, fcherik@chu-clermontferrand.fr

    Recruiting

  • Chu Dijon Bourgogne

    Dijon, 21000

    Laurence OLIVIER-FAIVRE, 0380295313, laurence.faivre@chu-dijon.fr

    Recruiting

  • CHU Dijon Bourgogne - CIC-P

    Dijon, 21079

    Active, not recruiting

  • CHU de Lille

    Lille, 59037

    Florence PETIT, 03 20 44 49 11, florence.petit@chu-lille.fr

    Recruiting

  • CHRU Nîmes

    Nîmes, 30029

    Camille CENNI, 04 66 68 68 68, camille.cenni@chu-nimes.fr

    Recruiting

  • AP-HP Hôpital Necker-Enfants Malades - CIC

    Paris, 75015

    Active, not recruiting

  • AP-HP Hôpital Necker-Enfants Malades

    Paris, 75015

    Guillaume CANAUD, 01 44 49 40 00, guillaume.canaud@inserm.fr

    Recruiting

  • CHU Rennes

    Rennes, 35023

    Alinoë LAVILLAUREIX, 02 99 26 67 44

    Recruiting

  • CHRU Tours

    Tours, 37044

    Annabel MARUANI, 02 47 47 90 76, annabel.maruani@univ-tours.fr

    Recruiting

Other trials in France

About this study

Official title: 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)

Read the detailed description

This study consists of a screening period up to 90 days, a first double-blind, placebo-controlled period of 6 months, followed by an open label period of alpelisib treatment, to reach a 24-month duration of treatment for all patients. The study will enroll 18-40 years old adults and 2-18 years old paediatric patients.

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.

Being tested
Alpelisib (BYL719), Matching placebo, Optional lumbar puncture + blood sample
Keywords
Neurodevelopmental disorders, alpelisib, therapeutic trial, PIK3CA, MCAP
Medical subject headings
Megalencephaly cutis marmorata telangiectatica congenita, Neurodevelopmental Disorders, Hereditary Sensory and Autonomic Neuropathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Alpelisib (BYL719)Drug

    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 placeboDrug

    During double-blind period of group A: matching placebo will be taken once a day each day over 6 months

  • Optional lumbar puncture + blood sampleProcedure or surgery

    Between 6 and 24 months of treatment with Alpelisib

Study groups in NCT05577754
Study groupRoleWhat they receive
Group APlacebo comparatorNot described
Receives: Drug: Alpelisib (BYL719); Drug: Matching placebo; Procedure: Optional lumbar puncture + blood sample
Group BExperimentalNot described
Receives: Drug: Alpelisib (BYL719); Procedure: Optional lumbar puncture + blood sample

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: At 24 months of treatment compared to baseline

Secondary outcomes (13)

  1. 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

    Measured: 6 months of treatment in double blind period

  2. Changes from baseline in brain volume, vascularization, structural connectivity

    Description of changes in brain volume, vascularization, structural connectivity, assessed by MRI

    Measured: baseline to end of treatment period

  3. Frequency and severity of adverse events

    Type, frequency, seriousness, and severity of adverse events per CTCAE v5.0 criteria

    Measured: Up to 34 months

  4. Proportion of participants with response at end of treatment

    Improvement of at least 4 points in the Vineland II Adaptive Behavior Scale (VABS-II)

    Measured: At 6, 12 and 18 months of treatment, compared to baseline

  5. Change in quality of life assessed by Pediatric Quality of Life Inventory 4.0 or San Martin questionnaires

    Pediatric Quality of Life Inventory 4.0 (PedSQL): The quality of life questionnaire PedSQL 4.0 consists of a modular approach to measuring health-related quality of life in healthy children and adolescents (ages range : 2-18 years). It is brief (23 items only). It takes less than 10 minutes to complete. This scale is designed to assess 4 dimensions: physical, emotional, social and school functioning. It is valid, reliable and sensitive to change.

    • The San Martin Scale is completed by parents or primary caregiver who knows well the person with ID, for at least three months. They have to rate each item on a 4-point scale (from 1= when the item is never true, to 4 = when it is always true). The questionnaire consists of 95 items, assessing eight dimensions of the quality of life

    Measured: At 6, 12, 18, 24 months of treatment, compared to baseline.

  6. Evolution of scores at visual analogue scale

    Measured: At 6, 12, 18, 24 months of treatment, compared to baseline.

  7. Evolution of Clinical Global Impression of severity (CGI-S)

    The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis.

    Measured: At 6, 12, 18, 24 months of treatment, compared to baseline.

  8. Evolution of Global improvement scores (CGI-I)

    The Clinical Global Impression - Improvement scale (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention

    Measured: At 6, 12, 18, 24 months of treatment, compared to baseline.

  9. Changes in neuropsychological scales adapted to age for attention, cognition, visuo-spatial disorders, fine motor skills, speech, reasoning and cognitive inhibition abilities

    Appropriate neuropsychological tests will be used according to the age of patients and their level of cognitive impairment. The tests were selected according to the conclusions of a working group from the DéfiScience Network (see link), which assessed all the neuropsychological tests available for each domain and adapted to ID patients, and the lack of sensitivity to placebo effect. In case of mild to moderate ID, appropriate Wechsler scale will be used. In case of severe ID, Revised-Brunet-Lézine scale will be used. Attention, visuo-spatial, language and fine motor skills will be assessed using subtests from Wechsler scales, NEPSY II and the Children Memory Scale or WMS IV for adults.

    Measured: At 12 and 24 months of treatment compared to baseline

  10. Changes in seizures frequency

    Evolution of number of epileptic seizures for affected patients and antiepileptic drugs use, assessed by a weekly diary

    Measured: At 6, 12, 18 and 24 months of treatment compared to baseline

  11. Changes in overgrowth or skin lesions

    Increase, no changes or reduction according to clinical measures and standardized photographs

    Measured: At 6, 12, 18 and 24 months of treatment compared to baseline

  12. Changes in Motor Function Measure (MFM) scores

    Motor Function Measure (MFM) is a comprehensive quantitative scale created to measure functional motor skills in a person with neuromuscular disease. It makes possible to classify patients in grade of severity in each of the 3 areas of motor function (D1: standing position and transfers, D2: axial and proximal motor skills, D3: distal motor skills).

    Measured: At 6, 12, 18 and 24 months of treatment compared to baseline

  13. Pharmacokinetic parameters of alpelisib (ng/mL) in cerebrospinal fluid (CSF) and blood

    Level of alpelisib (ng/mL) in CSF and in blood, and correlation estimate (rho) between CSF and blood levels of alpelisib

    Measured: Between 6 and 24 months of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Oct 2022
  2. Study start28 Nov 2022
  3. Primary completionMar 2027 (estimated)
  4. Study completionMar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05577754
Sponsor's protocol ID
OLIVIER FAIVRE Novartis 2021
Acronym
SESAM
Status last verified
Feb 2026
First submitted
10 Oct 2022
Last updated
24 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: All requests for the study's data will be considered by the SESAM trial steering committee.

Publications

  • 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.

    PubMed 26918704

  • 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.

    PubMed 39806603

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alpelisib (BYL719) and Optional lumbar puncture + blood sample in people with Megalencephaly-capillary Malformation Polymicrogyria Syndrome (MCAP), run by Centre Hospitalier Universitaire Dijon at 13 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Laurence OLIVIER-FAIVRE (0380295313, laurence.faivre@chu-dijon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of participants with response at end of treatment assessed by the Vineland II Adaptive Behavior Scale (VABS-II) (time frame: At 24 months of treatment compared to baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05577754, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2026.

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