ALPELISIB for PIK3CA-related overgrowth spectrum (PROS)

Inclusion criteria

• {"criterion_text":"- Patients who had previously participated in EPIK-P1\n- Signed informed consent form (ICF) and assent (when applicable) from the participant, parent, or guardian must be obtained prior to any study related screening procedures being performed.\n- Participant is treated with at least one dose of alpelisib after the EPIK-P1 study data cutoff date of 09-Mar-2020 -If participants discontinue treatment for safety reasons prior to the first visit for the prospective period of the current study and if the treatment cannot be restarted, but they consent for the retrospective period, only the retrospective data will be abstracted -If participants discontinue treatment for any other reason, including worsening of disease, prior to the first visit for the prospective period of the current study, and they consent to restart treatment as considered beneficial by the investigator, they are -eligible for both periods"}

Exclusion criteria

• {"criterion_text":"- 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.\n- For participants in the prospective period Previous alpelisib treatment discontinuation (after 09-Mar-2020) due to any of the following AEs -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 (QTcF) prolongation (>500 ms or >60 ms change from baseline)\n- For participants in the prospective period 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.\n- For participants in the prospective period Participant with uncontrolled diabetes mellitus (Type I or II) at time of informed consent."}

Primary endpoints

• {"endpoint_text":"- Incidence of new or worsening grade ≥3 treatment emergent AEs (by system organ class and preferred term)","definition_or_measurement_approach":"Incidence of new or worsening treatment-emergent adverse events of grade ≥3, collected and classified by system organ class (SOC) and preferred term (PT)."}

Secondary endpoints

• {"endpoint_text":"- Retrospective Period Only - Incidence, type and severity per common terminology criteria for AEs (CTCAE) v4.03 criteria, causality assessments of AEs, and other safety data including changes in laboratory values, vital signs and assessment of cardiac function.","definition_or_measurement_approach":"Assessment per CTCAE v4.03 for incidence/type/severity, causality assessments, lab changes, vital signs and cardiac function measures (retrospective period)."}
• {"endpoint_text":"- Prospective Period Only - Incidence, type and severity per CTCAE v4.03 criteria, causality assessments of AEs, and other safety data including changes in laboratory values, vital signs and assessment of cardiac function. Additionally, for this period only, growth, bone/dental development and sexual maturation (for applicable age) will be assessed.","definition_or_measurement_approach":"Assessment per CTCAE v4.03 for AEs and other safety data; plus longitudinal assessments of growth, bone/dental development and sexual maturation where age-applicable (prospective period)."}
• {"endpoint_text":"- Investigator assessment of lesion response as improved, stable or worsened.","definition_or_measurement_approach":"Investigator-rated categorical assessment of lesion response (improved, stable, worsened)."}
• {"endpoint_text":"- Incidence of PROS-related symptoms and complications/comorbidities among participants with symptoms and complications/comorbidities.","definition_or_measurement_approach":"Incidence counts of PROS-related symptoms and complications/comorbidities over time among affected participants."}
• {"endpoint_text":"- Number of healthcare visits/hospitalizations due to PROS.","definition_or_measurement_approach":"Count of healthcare visits and hospitalizations attributed to PROS over time."}
• {"endpoint_text":"- Description of medications and non-drug therapies received -PROS-related treatment(s) other than alpelisib -Medication(s) (e.g., concomitant PROS-related medications including medication for the management of PROS related complications as well as medications to manage complications secondary to alpelisib) -Non-drug treatment(s) -Alpelisib treatment -PROS-related surgeries","definition_or_measurement_approach":"Descriptive capture of medications and non-drug therapies received, including concomitant PROS-related medications, non-drug treatments, alpelisib treatment details and PROS-related surgeries."}

France

Earliest CTIS Part Ii Submission Date

02-04-2024

Latest Decision Or Authorization Date

16-12-2025

Processing Time Days

623

Number Of Sites

3

Number Of Participants

35

Ireland

Earliest CTIS Part Ii Submission Date

22-02-2024

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

706

Number Of Sites

1

Number Of Participants

1

Spain

Earliest CTIS Part Ii Submission Date

22-02-2024

Latest Decision Or Authorization Date

22-12-2025

Processing Time Days

669

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Rps Research Iberica S.L.

Responsibilities

sponsorDuties codes: 1

Name

Parexel International (IRL) Limited

Responsibilities

sponsorDuties codes: 12

Name

Icon Clinical Research Limited

Responsibilities

sponsorDuties codes: 1

Name

IQVIA Limited

Responsibilities

sponsorDuties codes: 1, 3

Name

Syneos Health Inc.

Responsibilities

sponsorDuties codes: 1

Name

Syneos Health Clinical Spain S.L.

Responsibilities

sponsorDuties codes: 1

Name

IQVIA RDS Spain S.L.

Responsibilities

sponsorDuties codes: 1

Third parties

• {"country":"Spain","full_name":"Rps Research Iberica S.L.","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties codes: 12","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: 1, 3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Syneos Health Clinical Spain S.L.","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"IQVIA RDS Spain S.L.","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Pharmaceutical company"}