Study Assessing Long-term Safety and Efficacy of Alpelisib in Patients With PIK3CA-Related Overgrowth Spectrum (PROS) Who Previously Participated in Study CBYL719F12002 (EPIK-P1)

NCT04980833 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: CBYL719F124012023-508522-95-00
• Study Type: interventional
• Target: 41
• Locations: 4 countries
• Sites: 6

Brief Summary

This is a prospective interventional Phase II multi center study, open label, preceded by a retrospective non-interventional period, to assess the long-term safety and efficacy of alpelisib, in pediatric and adult participants with PROS.

Conditions

PIK3CA-related Overgrowth Spectrum (PROS)

Keywords

PIK3CA-related overgrowth spectrum (PROS); Alpelisib; BYL719; Adult; Pediatric; Phase II

Outcome Measures

Primary Outcomes (1)

• Prospective period only: Proportion of participants with new or worsening grade ≥3 treatment emergent adverse events (AEs)

  Incidence of new or worsening grade ≥3 treatment emergent AEs (by system organ class and preferred term)

  From date of first interventional dose administration in the prospective period (Day 1) to 30 days after last dose of study drug, assessed up to 5 years.

Secondary Outcomes (8)

• Retrospective period: Proportion of participants with Adverse Events (AEs)

  From 10-Mar-2020 (1 day after EPIK-P1 data cut-off date) to the day before the first interventional dose of alpelisib is administered in the prospective period of this study (Day -1)

• Prospective period: Proportion of participants with AEs

  From Day 1 up to 5 years

• Retrospective and prospective period: Overall clinical assessment as assessed by the investigator

  Retrospective: From 10-Mar-2020 (1 day after EPIK-P1 data cut-off date) to the day before the first interventional dose of alpelisib is administered in the prospective period of this study (Day -1). Prospective: From Day 1 up to 5 years

• Retrospective and prospective period: Incidence of PROS-related symptoms and complications/comorbidities among participants with symptoms and complications/comorbidities.

  Retrospective: From 10-Mar-2020 (1 day after EPIK-P1 data cut-off date) to the day before the first interventional dose of alpelisib is administered in the prospective period of this study (Day -1). Prospective: From Day 1 up to 5 years

• Retrospective and prospective period: Proportion of participants with healthcare visits/hospitalizations due to PROS.

  Retrospective: From 10-Mar-2020 (1 day after EPIK-P1 data cut-off date) to the day before the first interventional dose of alpelisib is administered in the prospective period of this study (Day -1). Prospective: From Day 1 up to 5 years

Study Arms (1)

Alpelisib

EXPERIMENTAL

All participants will receive alpelisib once a day

Drug: Alpelisib

Interventions

Alpelisib DRUG

Participant's treatment plan has been established by the treating physician, within the global compassionate use framework. Doses permitted are 50, 125, 200 and 250 mg.

Also known as: BYL719

Alpelisib

Eligibility Criteria

• Age: 2 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who had previously participated in the study EPIK-P1.
• Signed informed consent form and assent (when applicable) from the participant, parent, or guardian must be obtained prior to any study related screening procedures being performed.
• Participant is treated with at least one dose of alpelisib after the EPIK-P1 study data cut- off date of 09-Mar-2020.

You may not qualify if:

• For participants in the retrospective period
• \- All EPIK-P1 participants who permanently discontinued the investigational drug on or prior to the cut-off date 09-Mar-2020.
• For participants in the prospective period
• Previous alpelisib treatment discontinuation (after 09-Mar-2020) due to any of the following adverse events:
• Grade 4 skin and subcutaneous tissue disorders
• Stevens-Johnson-Syndrome (SJS)/ Toxic Epidermal Necrolysis (TEN) or other SJS/TEN-like severe skin reactions (any grade)
• Grade 4 hyperglycemia without confounding factors
• Pneumonitis (any grade)
• Grade 4 stomatitis
• Grade 4 pancreatitis
• Recurrent grade 4 thrombocytopenia
• Grade 3 or 4 serum creatinine increase
• Grade 4 isolated total bilirubin elevation
• Recurrent grade 3 or 4 QT interval corrected by Fridericia's formula prolongation (\>500 ms or \>60 ms change from baseline)
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (6)

Boston Childrens Hospital

Boston, Massachusetts, 02215, United States

Location

Novartis Investigative Site

Dijon, 21000, France

Location

Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Dublin, 12, Ireland

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

MeSH Terms

Interventions

Alpelisib

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: July 28, 2021
• Study Start: January 27, 2022
• Primary Completion (Estimated): August 20, 2027
• Study Completion (Estimated): August 20, 2027
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

ES (1); FR (3); US (1); IE (1)