Study Description
The main purpose of this study in participants with PIK3CA-mutated lymphatic
malformations (LyM) is to assess the change in radiological response and symptom severity
upon treatment with alpelisib as compared to placebo. This is a phase II/III multi-center study with two stages:
- Stage 1 is designed to select the dose(s) for the confirmatory phase (DSCP) for
alpelisib in Stage 2 and will comprise a 24-week open-label core phase in adult (≥18
years of age) and pediatric participants (6-17 years of age) with PIK3CA-mutated
LyM, followed by an extension. After eligibility has been confirmed at screening,
participants will be randomized to the different alpelisib doses according to their
age. Depending on the results at the end of Stage 1 core phase, the Stage 2 will be
opened to adult and/or pediatric participants or the study may be stopped.
- Stage 2 is designed to confirm the efficacy and assess safety of alpelisib at the
DSCP in participants with PIK3CA-mutated LyM and will comprise a 24-week randomized,
double blind, placebo-controlled confirmatory phase in adult (≥18 years of age) and
pediatric participants 6-17 years of age followed by an open-label extension. After
eligibility has been confirmed at screening participants will be randomized to
alpelisib or placebo.
Additionally, in parallel, Stage 2 will include a 24-week open-label core phase in
pediatric participants 2-5 years of age followed by an extension, if pediatric
participants will be enrolling in Stage 2.
Based on the results of the 24-week open-label core phase of Stage 1, the dose(s) for
Stage 2 will be selected by Novartis in consultation with the Steering Committee (SC).
During the 24-week randomized, double blind, placebo-controlled core phase of Stage 2, an
Independent Data Monitoring Committee (DMC) will conduct periodic safety reviews.
Interventions
Alpelisib
Placebo
Eligibility Criteria
Key Inclusion Criteria:
- Participant must be willing to remain at the clinical site as required by the
protocol and be willing to adhere to study restrictions and examination schedules.
- Participant has a physician confirmed and documented diagnosis of a LyM at the time
of informed consent
- Participant is not considered as a candidate for or is not willing to receive local
therapy options including but not limited to sclerotherapy, embolization, and
surgery until the completion of Week 24 in Stage 1 and 2.
- Participant has evidence of a somatic mutation(s) in the PIK3CA gene
- Participant has at least one measurable LyM lesion confirmed by BIRC assessment
prior to randomization.
Key Exclusion Criteria:
- Participant has a physician-confirmed and documented diagnosis of PROS at the time
of informed consent.
- 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.
- Participant has a known history of Stevens-Johnson syndrome, erythema multiforme, or
toxic epidermal necrolysis at the time of informed consent.
- Participant has an established diagnosis of type I diabetes mellitus or uncontrolled
type II diabetes mellitus at the time of informed consent.
- 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.
Other inclusion/exclusion criteria may apply
Worldwide Contacts
If the location of your choosing does not feature any contact detail, please reach out using the information below.