RecruitingPhase 2Phase 3NCT05948943

Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.

A Two-stage Double-blind, Randomized, Placebo-controlled Study to Assess the Efficacy, Safety and Pharmacokinetics of Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.


Sponsor

Novartis Pharmaceuticals

Enrollment

232 participants

Start Date

Nov 24, 2023

Study Type

INTERVENTIONAL

Conditions

Summary

The main purpose of this study in participants with PIK3CA-mutated LyM is to assess the change in radiological response and symptom severity upon treatment with alpelisib film-coated tablets (FCT) as compared to placebo.


Eligibility

Min Age: 0 YearsMax Age: 100 Years

Inclusion Criteria7

  • Signed informed consent and assent (when applicable) from the participant, parent, legal authorized representative or guardian.
  • 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 symptomatic LyM at the time of informed consent (Note: the physician must confirm that the LyM cannot be included under the PROS diagnostic criteria).
  • 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 in Stage 1 and 2.
  • Participant has evidence of a somatic mutation(s) in the PIK3CA gene prior to randomization.
  • Participant has at least one measurable LyM lesion confirmed by BIRC assessment prior to randomization.
  • Participants must be able to ingest study drug (either in tablet form or as a drinkable 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 Criteria5

  • 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.

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Interventions

DRUGAlpelisib

In Stage 1: adult participants (≥18 years of age) will receive dose 1 or dose 2 of alpelisib; pediatric participants (6-17 years of age) will receive dose 2 or dose 3 of alpelisib. In Stage 2: Adult participants will receive alpelisib at the dose selected for confirmatory phase in adult participants; pediatric participants (6-17 years of age) will will receive alpelisib at the dose selected for confirmatory phase in pediatric participants; and pediatric participants of 0-5 years of age will receive dose 3 of alpelisib

DRUGPlacebo

In Stage 2, participants will receive matching placebo for 24 weeks of the study


Locations(49)

UCSF Benioff Children s Hospital

Oakland, California, United States

Lucile Packard Childrens Hosp

Palo Alto, California, United States

Childrens National Medical Center

Washington D.C., District of Columbia, United States

Nemours Childrens Clinic

Jacksonville, Florida, United States

Childrens Hosp Boston Dept of Heme

Boston, Massachusetts, United States

WA Uni School Of Med

St Louis, Missouri, United States

Cinn Children Hosp Medical Center

Cincinnati, Ohio, United States

Univ Hospital Of Cleveland

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Nationwide Children s Hospital

Columbus, Ohio, United States

Oregon Health Science University

Portland, Oregon, United States

CHOP Abramson Pediatric Resch Ctr

Philadelphia, Pennsylvania, United States

Childrens Hosp Pittsburgh UPMC

Pittsburgh, Pennsylvania, United States

Baylor College Of Medicine

Houston, Texas, United States

U of TX Health Science Ct

Houston, Texas, United States

Childrens Hospital and Regional Medical Center

Seattle, Washington, United States

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

Capital Federal, Argentina

Novartis Investigative Site

Sydney, New South Wales, Australia

Novartis Investigative Site

Sydney, New South Wales, Australia

Novartis Investigative Site

Brisbane, Queensland, Australia

Novartis Investigative Site

Brussels, Belgium

Novartis Investigative Site

Bordeaux, France

Novartis Investigative Site

Bron, France

Novartis Investigative Site

Caen, France

Novartis Investigative Site

Dijon, France

Novartis Investigative Site

Lille, France

Novartis Investigative Site

Marseille, France

Novartis Investigative Site

Montpellier, France

Novartis Investigative Site

Paris, France

Novartis Investigative Site

Paris, France

Novartis Investigative Site

Toulouse, France

Novartis Investigative Site

Tours, France

Novartis Investigative Site

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Novartis Investigative Site

Mannheim, Baden-Wurttemberg, Germany

Novartis Investigative Site

Cologne, North Rhine-Westphalia, Germany

Novartis Investigative Site

Leipzig, Saxony, Germany

Novartis Investigative Site

Berlin, Germany

Novartis Investigative Site

Bologna, BO, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Naples, Italy

Novartis Investigative Site

Rotterdam, South Holland, Netherlands

Novartis Investigative Site

Esplugues, Barcelona, Spain

Novartis Investigative Site

A Coruña, Spain

Novartis Investigative Site

Madrid, Spain

Novartis Investigative Site

Madrid, Spain

Novartis Investigative Site

Lausanne, Switzerland

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NCT05948943


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