A research study to find out if the study treatment alpelisib (BYL719) is safe for a long period of time for who has confirmed diagnosis of PIK3CA-related overgrowth spectrum (PROS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

27 Jan 2022 → ongoing

Decision date (initial)

2024-04-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-508522-95-00

EudraCT number

2020-005896-12

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Prospective period only - To assess the long-term safety and tolerability of alpelisib over time.

Secondary objectives 3

1. Retrospective period only - To assess the safety and tolerability of alpelisib
2. Prospective period only - To assess the safety and tolerability of alpelisib over time
3. 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

Conditions and MedDRA coding

PIK3CA-Related Overgrowth Spectrum (PROS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Patients who had previously participated in EPIK-P1
2. 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.
3. 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 4

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 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)
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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 6

1. 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.
2. 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.
3. Investigator assessment of lesion response as improved, stable or worsened.
4. Incidence of PROS-related symptoms and complications/comorbidities among participants with symptoms and complications/comorbidities.
5. Number of healthcare visits/hospitalizations due to PROS.
6. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 7

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 40 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications