Clinical trial • Phase II/III • Haematology|Rare Disease

ALPELISIB for Lymphatic malformation associated with PIK3CA mutation|Lymphangioma

Phase II/III trial of ALPELISIB for Lymphatic malformation associated with PIK3CA mutation|Lymphangioma.

Overview

Trial Therapeutic Area
Haematology|Rare Disease
Trial Disease
Lymphatic malformation associated with PIK3CA mutation|Lymphangioma
Trial Stage
Phase II/III
Drug Modality
Small molecule
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
04-09-2023
First CTIS Authorization Date
10-01-2024

Trial design

Randomised, open-label, placebo to byl719 (matching placebo to byl719 50 mg, 125 mg, 200 mg film-coated tablets) used in the double-blind, placebo-controlled confirmatory phase (stage 2 groups 3 and 4)., adaptive Phase II/III trial in France, Netherlands, Germany and others.

Randomised
Yes
Open Label
Yes
Comparator
Placebo to BYL719 (matching placebo to BYL719 50 mg, 125 mg, 200 mg film-coated tablets) used in the double-blind, placebo-controlled confirmatory phase (Stage 2 groups 3 and 4).
Adaptive
True, Stage 1 is a dose selection stage (select the dose(s) for the confirmatory phase, DSCP) and is used to identify dose(s) for Stage 2; Stage 2 includes blinded placebo-controlled confirmatory phase with switching of placebo participants to active treatment at Week 24.
Biomarker Stratified
True, biomarker: PIK3CA mutation (participants must have evidence of a somatic PIK3CA mutation prior to randomization).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
162
Trial Duration For Participant
168

Eligibility

Recruits 162 paediatric patients.

Vulnerable Population
Vulnerable populations include pediatric participants (age groups 0-5, 6-17). Consent/assent handling: "Signed informed consent and assent (when applicable) from the participant, parent, legal authorized representative or guardian." Age-specific informed consent and assent forms are provided (Main ICF - Adult, Parent Legal Guardian ICFs, Child Assent, Adolescent Assent). Documents available in multiple languages per country-specific submissions.

Inclusion criteria

  • {"criterion_text":"- Signed informed consent and assent (when applicable) from the participant, parent, legal authorized representative or guardian."}
  • {"criterion_text":"- Participant must be willing to remain at the clinical site as required by the protocol and to adhere to study restrictions and examination schedules."}
  • {"criterion_text":"- Participant has a physician confirmed and documented diagnosis of a symptomatic LyM at the time of informed consent (Note: the physician must confirm that the LyM cannot be included under the PROS diagnostic criteria)."}
  • {"criterion_text":"- Participant is not considered as a candidate for or is not willing to receive non-drug therapies including but not limited to sclerotherapy, embolization, and surgery until the completion of Week 24 at the time of informed consent."}
  • {"criterion_text":"- Participant has evidence of a somatic mutation(s) in the PIK3CA gene prior to randomization."}
  • {"criterion_text":"- Participant has at least one measurable LyM lesion confirmed by BIRC assessment prior to randomization."}
  • {"criterion_text":"- Participants must be able to ingest study drug in tablet or as an oral suspension (Groups 1 to 4) or granules or as an oral suspension (Group 5) as assessed within 7 days before study treatment start. Drug administration via feeding tubes is allowed."}

Exclusion criteria

  • {"criterion_text":"- Participant has a physician-confirmed and documented diagnosis of PROS at the time of informed consent."}
  • {"criterion_text":"- Participant has a physician-confirmed and documented diagnosis of a Central Conducting Lymphatic Anomaly, General Lymphatic Anomaly, Gorham-Stout disease, Kaposiform lymphangiomatosis at the time of informed consent."}
  • {"criterion_text":"- Participant has a known history of Stevens-Johnson syndrome, erythema multiforme, or toxic epidermal necrolysis at the time of informed consent."}
  • {"criterion_text":"- Participant has an established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus at the time of informed consent."}
  • {"criterion_text":"- Participant had previous treatment with alpelisib and/or any other PI3K inhibitors with treatment duration longer than 2 weeks at the time of informed consent."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Response (yes/no) at Week 24 (confirmatory phase) of Stage 2, defined by achieving at least 20% reduction in the sum of target lesion volumes (1 to 3 lesions), assessed by MRI by a blinded independent review committee (BIRC) at Week 24, provided that none of the individual target lesions has at least 20% increase from baseline and in absence of progression of non-target lesions and without new lesions.","definition_or_measurement_approach":"Radiological response assessed by MRI by a Blinded Independent Review Committee (BIRC) at Week 24; response defined as ≥20% reduction in sum of target lesion volumes (1-3 lesions) with no individual target lesion showing ≥20% increase versus baseline, no progression of non-target lesions, and no new lesions."}

Secondary endpoints

  • {"endpoint_text":"- Response (yes/no) at Week 24 (confirmatory phase) of Stage 2 defined by achieving at least a 1-point improvement compared to baseline on the patient global impression of severity (PGI-S) scale.","definition_or_measurement_approach":"Patient-reported outcome: PGI-S scale; response = ≥1-point improvement from baseline at Week 24 in the confirmatory phase of Stage 2."}
  • {"endpoint_text":"- Response at Week 24 of Stage 2, defined by achieving at least 20% reduction in the sum of target lesion volumes (1 to 3 lesions), assessed by MRI by a BIRC at Week 24, provided that none of the individual target lesions has at least 20% increase from baseline and in absence of progression of non-target lesions and without new lesions.","definition_or_measurement_approach":"Radiological response assessed by MRI by a BIRC at Week 24; same definition as primary radiological response (≥20% reduction in sum of target lesion volumes with no individual lesion ≥20% increase, no progression of non-target lesions, no new lesions)."}

Recruitment

Planned Sample Size
162
Recruitment Window Months
112
Consent Approach
Informed consent is obtained from the participant or from a parent/legal authorised representative or guardian as applicable; assent is obtained when applicable. Age-specific ICFs and assent forms are provided (Main ICF - Adult; Parent Legal Guardian ICF; Child Assent; Adolescent Assent). Country- and language-specific ICFs are available (documents in English, French, Italian, Spanish, German, Dutch as indicated in submission documents).

Geography

Total Number Of Sites
37
Total Number Of Participants
162

France

Earliest CTIS Part Ii Submission Date
11-12-2023
Latest Decision Or Authorization Date
22-01-2026
Processing Time Days
773
Number Of Sites
14
Number Of Participants
57

Sites

Site Name
Assistance Publique Hopitaux De Marseille
Department Name
3105: CHU Timone, Département de Dermatologie
Principal Investigator Name
Stéphanie Mallet
Principal Investigator Email
Stephanie.MALLET@ap-hm.fr
Contact Person Name
Stéphanie Mallet
Contact Person Email
Stephanie.MALLET@ap-hm.fr
Site Name
Hospices Civils De Lyon
Department Name
3101: Hôpital Femme Mère Enfant Département Médical
Principal Investigator Name
Laurent Guibaud
Principal Investigator Email
laurent.guibaud@chu-lyon.fr
Contact Person Name
Laurent Guibaud
Contact Person Email
laurent.guibaud@chu-lyon.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
3109: Département de médecine vasculaire - Hôpital Rangueil
Principal Investigator Name
Julie Malloizel-Delaunay
Principal Investigator Email
Malloizel-delaunay.j@chu-toulouse.fr
Contact Person Name
Julie Malloizel-Delaunay
Site Name
Pellegrin Hospital
Department Name
3102: Unité de Dermatologie Pédiatrique
Principal Investigator Name
Christine Labrèze
Principal Investigator Email
christine.labreze@chu-bordeaux.fr
Contact Person Name
Christine Labrèze
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
3100: Hôpital Clocheville, Département de Médecine Pédiatrique
Principal Investigator Name
Annabel Maruani
Principal Investigator Email
annabel.maruani@univ-tours.fr
Contact Person Name
Annabel Maruani
Contact Person Email
annabel.maruani@univ-tours.fr
Site Name
Centre Hospitalier Universitaire D'Angers
Department Name
3111: Département Dermatologie
Principal Investigator Name
Ludovic MARTIN
Principal Investigator Email
Lumartin@chu-angers.fr
Contact Person Name
Ludovic MARTIN
Contact Person Email
Lumartin@chu-angers.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
3103: Hôpital Lariboisière, Département de Neuroradiologie
Principal Investigator Name
Annouk Bisdorff
Principal Investigator Email
annouk.bisdorff@aphp.fr
Contact Person Name
Annouk Bisdorff
Contact Person Email
annouk.bisdorff@aphp.fr
Site Name
Hopital Necker Enfants Malades
Department Name
3104: Département Néphrologie Adultes
Principal Investigator Name
Guillaume Canaud
Principal Investigator Email
Guillaume.canaud@inserm.fr
Contact Person Name
Guillaume Canaud
Contact Person Email
Guillaume.canaud@inserm.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
3106: Institut Coeur Poumon, Département Physiologie Cardio Vasculaire
Principal Investigator Name
Caroline Chopinet
Principal Investigator Email
Caroline.CHOPINET@chu-lille.fr
Contact Person Name
Caroline Chopinet
Contact Person Email
Caroline.CHOPINET@chu-lille.fr
Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
3110: Département Génétique Médicale
Principal Investigator Name
Laurence Olivier-Faivre
Principal Investigator Email
Laurence.faivre@chu-djon.fr
Contact Person Name
Laurence Olivier-Faivre
Contact Person Email
Laurence.faivre@chu-djon.fr
Site Name
Hopital Saint Eloi
Department Name
3107: Service de Médecine Vasculaire
Principal Investigator Name
Isabelle Quere
Principal Investigator Email
i-quere@chu-montpellier.fr
Contact Person Name
Isabelle Quere
Contact Person Email
i-quere@chu-montpellier.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
3106: Sérvice d’ORL Pédiatrique Hôpital Jeanne de Flandre
Principal Investigator Name
Caroline Chopinet
Principal Investigator Email
Caroline.CHOPINET@chu-lille.fr
Contact Person Name
Caroline Chopinet
Contact Person Email
Caroline.CHOPINET@chu-lille.fr
Site Name
Centre Hospitalier Universitaire De Caen Normandie
Department Name
3108: Département Dermatologie
Principal Investigator Name
Anne Dompmartin
Principal Investigator Email
dompmartin-a@chu-caen.fr
Contact Person Name
Anne Dompmartin
Contact Person Email
dompmartin-a@chu-caen.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
3109: Département Dermatologie
Principal Investigator Name
Julie Malloizel-Delaunay
Principal Investigator Email
Malloizel-delaunay.j@chu-toulouse.fr
Contact Person Name
Julie Malloizel-Delaunay

Netherlands

Earliest CTIS Part Ii Submission Date
03-04-2024
Latest Decision Or Authorization Date
13-03-2026
Processing Time Days
709
Number Of Sites
2
Number Of Participants
18

Sites

Site Name
Stichting Radboud University Medical Center
Department Name
#3400: Department of pediatrics
Principal Investigator Name
Bas Henk Verhoeven
Principal Investigator Email
bas.verhoeven@radboudumc.nl
Contact Person Name
Bas Henk Verhoeven
Contact Person Email
bas.verhoeven@radboudumc.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
#3401: Department of pediatric dermatology
Principal Investigator Name
E.M. (Elyse) Verboom
Principal Investigator Email
e.verboom@erasmusmc.nl
Contact Person Name
E.M. (Elyse) Verboom
Contact Person Email
e.verboom@erasmusmc.nl

Germany

Earliest CTIS Part Ii Submission Date
28-11-2023
Latest Decision Or Authorization Date
29-04-2026
Processing Time Days
883
Number Of Sites
6
Number Of Participants
21

Sites

Site Name
Universitaet Leipzig
Department Name
3201:Klinik und Poliklinik für Kinder- und Jugendmedizin
Principal Investigator Name
Susanne Wendt
Principal Investigator Email
Susanne.wendt@medizin.uni-leipzig.de
Contact Person Name
Susanne Wendt
Site Name
Universitaetsklinikum Ulm AöR
Department Name
3206: HNO-Klinik, Kopf- und Halschirurgie
Principal Investigator Name
Adrian von Witzleben
Principal Investigator Email
Adrian.vonWitzleben@uniklinik-ulm.de
Contact Person Name
Adrian von Witzleben
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
3205: Klinik für Pädiatrie mit Schwerpunkt Hämatologie/ Onkologie
Principal Investigator Name
Susanne Holzhauer
Principal Investigator Email
Susanne.holzhauer@charite.de
Contact Person Name
Susanne Holzhauer
Contact Person Email
Susanne.holzhauer@charite.de
Site Name
Universitat Heidelberg
Department Name
3202:Klinik für Radiologie und Nuklearmedizin
Principal Investigator Name
Maliha Sadick
Principal Investigator Email
Maliha.sadick@medma.uni-heidelberg.de
Contact Person Name
Maliha Sadick
Site Name
Medical Center - University Of Freiburg
Department Name
3200: Zentrum für Kinder- und Jugendmedizin
Principal Investigator Name
Friedrich Kapp
Principal Investigator Email
Friedrich.kapp@uniklinik-freiburg.de
Contact Person Name
Friedrich Kapp
Site Name
University Hospital Cologne AöR
Department Name
3204:Klinik und Poliklinik für Kinder- und Jugendmedizin
Principal Investigator Name
Boris Decarolis
Principal Investigator Email
boris.decarolis@uk-koeln.de
Contact Person Name
Boris Decarolis
Contact Person Email
boris.decarolis@uk-koeln.de

Italy

Earliest CTIS Part Ii Submission Date
21-11-2023
Latest Decision Or Authorization Date
13-05-2026
Processing Time Days
904
Number Of Sites
6
Number Of Participants
21

Sites

Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
3302: UOC Dermatologia Università degli Studi
Principal Investigator Name
Iria Neri
Principal Investigator Email
iria.neri@aosp.bo.it
Contact Person Name
Iria Neri
Contact Person Email
iria.neri@aosp.bo.it
Site Name
Ospedale Pediatrico Bambino Gesu'
Department Name
3300: UOC Trials (Pad. Salviati 1° piano)
Principal Investigator Name
Andrea Diociaiuti
Principal Investigator Email
andrea.diociaiuti@opbg.ne
Contact Person Name
Andrea Diociaiuti
Contact Person Email
andrea.diociaiuti@opbg.ne
Site Name
L’Azienda Ospedaliera Di Rilievo Nazionale Santobono-Pausilipon
Department Name
3303: UOC Pediatria Generale e Dermo-Immuno- Reumatologia
Principal Investigator Name
Luigi Martemucci
Principal Investigator Email
lmartemucci230@gmail.com
Contact Person Name
Luigi Martemucci
Contact Person Email
lmartemucci230@gmail.com
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
3305: Unità di Genetica Clinica Pediatrica
Principal Investigator Name
Alessandro Mussa
Principal Investigator Email
Alessandro.mussa@unito.it
Contact Person Name
Alessandro Mussa
Contact Person Email
Alessandro.mussa@unito.it
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
3304: S.S.D. Dermatologia Pediatrica Università degli Studi
Principal Investigator Name
Riccardo Cavalli
Principal Investigator Email
riccardo.cavalli@policlinico.mi.it
Contact Person Name
Riccardo Cavalli
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
3301: UOSA Malattie Rare di Transizione Dip. Salute della Donna del Bambino e Sanità Pubblica
Principal Investigator Name
Chiara Leoni
Principal Investigator Email
chiara.leoni@policlinicogemelli.it
Contact Person Name
Chiara Leoni

Spain

Earliest CTIS Part Ii Submission Date
24-11-2023
Latest Decision Or Authorization Date
13-05-2026
Processing Time Days
901
Number Of Sites
7
Number Of Participants
27

Sites

Site Name
Hospital Universitari Vall D Hebron
Department Name
3504: Medicina interna
Principal Investigator Name
Maria Camprodón Gómez
Principal Investigator Email
maria.camprodon@vallhebron.cat
Contact Person Name
Maria Camprodón Gómez
Contact Person Email
maria.camprodon@vallhebron.cat
Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
3503: Cirujano Plástico Pediátrico
Principal Investigator Name
Manuel Gómez Tellado
Principal Investigator Email
manuel.gomez.tellado@sergas.es
Contact Person Name
Manuel Gómez Tellado
Contact Person Email
manuel.gomez.tellado@sergas.es
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
3502: Dermatology
Principal Investigator Name
Minia Campos Dominguez
Principal Investigator Email
minia.campos@salud.madrid.org
Contact Person Name
Minia Campos Dominguez
Contact Person Email
minia.campos@salud.madrid.org
Site Name
Bellvitge University Hospital
Department Name
3505: Dermatología
Principal Investigator Name
Anna Jucglà Serra
Principal Investigator Email
ajucgla@bellvitgehospital.cat
Contact Person Name
Anna Jucglà Serra
Contact Person Email
ajucgla@bellvitgehospital.cat
Site Name
Hospital Universitario La Paz
Department Name
3500: Pediatric Surgery
Principal Investigator Name
Juan Carlos López Gutiérrez
Principal Investigator Email
queminfantil.hulp@salud.madrid.org
Contact Person Name
Juan Carlos López Gutiérrez
Site Name
University Hospital Son Espases
Department Name
3506: Cirugía pediátrica
Principal Investigator Name
Maria de los Angeles Muñoz Miguelsanz
Principal Investigator Email
mariadelosangeles.munozmiguelsanz@ssib.es
Contact Person Name
Maria de los Angeles Muñoz Miguelsanz
Site Name
Sant Joan De Deu Barcelona Hospital
Department Name
3501: Dermatology
Principal Investigator Name
Eulalia Baselga Torres
Principal Investigator Email
eulalia.baselga@sjd.es
Contact Person Name
Eulalia Baselga Torres
Contact Person Email
eulalia.baselga@sjd.es

Belgium

Earliest CTIS Part Ii Submission Date
04-03-2024
Latest Decision Or Authorization Date
22-04-2026
Processing Time Days
779
Number Of Sites
1
Number Of Participants
14

Sites

Site Name
Cliniques Universitaires Saint-Luc
Department Name
#3001: Centre de malformations vasculaires congenitales
Principal Investigator Name
Emmanuel Seront
Principal Investigator Email
emmanuel.seront@saintluc.uclouvain.be
Contact Person Name
Emmanuel Seront

Czechia

Earliest CTIS Part Ii Submission Date
11-03-2026
Latest Decision Or Authorization Date
13-05-2026
Processing Time Days
63
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
Fakultni Nemocnice Brno
Department Name
3700: Klinika detske onkologie
Principal Investigator Name
Peter Mudry
Principal Investigator Email
Mudry.Peter@fnbrno.cz
Contact Person Name
Peter Mudry
Contact Person Email
Mudry.Peter@fnbrno.cz

Sponsor

Primary sponsor

Full Name
Novartis Pharma AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
Parexel International (IRL) Limited
Name
Icon Clinical Research Limited
Name
Iqvia Rds Inc.
Name
Veeda Clinical Research Limited
Responsibilities
Pharmacokinetic sample analysis

Third parties

  • {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Jumo Health USA Inc.","duties_or_roles":"Patient recruitment and retention","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"eCOA, providing the electronic tablet for patients","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Adelphi Values Limited","duties_or_roles":"Patient embedded interviews vendor","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Independent central LyM image review and analysis","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"India","full_name":"Veeda Clinical Research Limited","duties_or_roles":"Pharmacokinetic sample analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Qualitymetric Incorporated LLC","duties_or_roles":"Validation of selected PROs for LyM indication","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Iqvia Rds Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Reimbursement and Transportation Support","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Italy","full_name":"Opis S.r.l.","duties_or_roles":"TMF archive","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"PRO translations and licensing","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
BYL719 (film-coated tablet, granules)
Active Substance
ALPELISIB
Modality
Small molecule
Routes Of Administration
Oral (ORAL USE)
Route
Oral
Authorisation Status
Authorised
Orphan Designation
Yes
Dose Levels
Product entries include max daily doses up to 250 mg for tablets and up to 50 mg for granules (as recorded in product data).
Maximum Dose
250 mg (max daily dose amount recorded for some tablet presentations); 50 mg (max daily dose for some granule presentations)
Investigational Product Name
Placebo to BYL719 200 mg film-coated tablets
Modality
Other
Investigational Product Name
Placebo to BYL719 125 mg film-coated tablets
Modality
Other
Investigational Product Name
Placebo to BYL719 50 mg film-coated tablets
Modality
Other

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