E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
PIK3CA-related overgrowth spectrum (PROS) |
|
E.1.1.1 | Medical condition in easily understood language |
PROS is a wide group of clinically recognizable mutation-driven malformations |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10081236 |
E.1.2 | Term | PIK3CA related overgrowth spectrum |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Prospective period only: To assess the long-term safety and tolerability of alpelisib over time.
|
|
E.2.2 | Secondary objectives of the trial |
● Retrospective period only: To assess the safety and tolerability of alpelisib. ● Prospective period only: To assess the safety and tolerability of alpelisib over time. ● Retrospective and prospective period: To evaluate the long-term efficacy of alpelisib To assess symptoms and complications/comorbidities associated with PROS over time. To assess the frequency of healthcare visits/hospitalizations due to PROS over time. To assess type of medications and non-drug therapies over time.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participants who had previously participated in the study EPIK-P1. 2. 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. 3. Participant is treated with at least one dose of alpelisib after the EPIK-P1 study data cut-off 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
|
|
E.4 | Principal exclusion criteria |
1. 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. 2. 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) 3. 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. 4. For participants in the prospective period: Participant with uncontrolled diabetes mellitus (Type I or II) at time of informed consent.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of new or worsening grade ≥3 treatment emergent AEs (by system organ class and preferred term) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Proportion of participants with an incidence of a grade ≥3 AE annually. Participants will be followed for at least 5 years in the prospective period of the study or until discontinuation of treatment |
|
E.5.2 | Secondary end point(s) |
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.
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.
Retrospective and prospective period: ● Investigator assessment of lesion response as improved, stable or worsened. ● Incidence of PROS-related symptoms and complications/comorbidities among participants with symptoms and complications/comorbidities. ● Number of healthcare visits/hospitalizations due to PROS. ● 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) (e.g., feeding tube, ketogenic diet, non-invasive device for sleep apnea, sclerotherapy, endovascular occlusive procedures) - Alpelisib treatment (e.g., dose, dose adjustments, duration of treatment, dose interruptions, discontinuation) - PROS-related surgeries (e.g., de-bulking or vascular surgery as well as the intended site of the procedure)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Proportion of participants with an incidence of a grade ≥3 AE annually. Participants will be followed for at least 5 years in the prospective period of the study or until discontinuation of treatment |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Retrospective period: non-interventional; prospective period: interventional |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
France |
Ireland |
Spain |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study for a given participant when the participant permanently discontinues study treatment with alpelisib and all the end of study procedures are completed (including the 30 days safety follow-up). The end of the overall study is defined as the time point when data collection will stop and the analysis of the study will occur. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 11 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |