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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05948943




Registration number
NCT05948943
Ethics application status
Date submitted
4/07/2023
Date registered
17/07/2023

Titles & IDs
Public title
Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.
Scientific title
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.
Secondary ID [1] 0 0
2023-504146-60-00
Secondary ID [2] 0 0
CBYL719P12201
Universal Trial Number (UTN)
Trial acronym
EPIK-L1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphatic Malformations 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Reproductive Health and Childbirth 0 0 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Alpelisib
Treatment: Drugs - Placebo

Experimental: Adult participants, alpelisib dose 1 (Stage 1) - Adult participants (=18 years of age) who will receive dose 1 of alpelisib an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1)

Experimental: Adult participants, alpelisib dose 2 (Stage 1) - Adult participants (=18 years of age) who will receive dose 2 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1).

Experimental: Pediatric participants (6-17 years of age), alpelisib dose 2 (Stage 1) - Pediatric participants 6-17 years of age who will receive dose 2 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1)

Experimental: Pediatric participants (6-17 years of age), alpelisib dose 3 (Stage 1) - Pediatric participants 6-17 years of age who will receive dose 3 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1).

Experimental: Adult participants, alpelisib (Stage 2) - Adult participants (=18 years of age) who will receive alpelisib at the dose selected for confirmatory phase in adult participants (Stage 2)

Placebo comparator: Adult participants, placebo (Stage 2) - Adult participants (=18 years of age) who will receive matching placebo

Experimental: Pediatric participants (6-17 years of age), alpelisib (Stage 2) - Pediatric participants (6-17 years of age) who will receive alpelisib at the dose selected for confirmatory phase in pediatric participants (Stage 2)

Placebo comparator: Pediatric participants (6-17 years of age), placebo (Stage 2) - Pediatric participants (6-17 years of age) who will receive matching placebo

Experimental: Pediatric participants (2-5 years of age), alpelisib (Stage 2) - Pediatric participants of 2-5 years who will dose 3 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier


Treatment: Drugs: Alpelisib
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 2-5 years of age will receive dose 3 of alpelisib

Treatment: Drugs: Placebo
In Stage 2, participants will receive matching placebo for 24 weeks of the study
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Stage 2:Radiological response rate at Week 24 of Stage 2 (adult and pediatric (6 - 17 years of age) participants)
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [1] 0 0
Stage 2: Percentage of participants with at least a 1-point improvement compared to baseline based on patient global impression of severity (PGI-S) scale at Week 24 of Stage 2 (adult and pediatric (6 - 17 years of age) participants)
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Stage 2: Percentage of participants with a radiological response at Week 24 of Stage 2 (pediatric participants 2-5 years of age)
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [3] 0 0
Stage 2: Change from baseline in patient global impression of change (PGI-C) scale (adult and pediatric (6-17 years of age) participants)
Timepoint [3] 0 0
Up to approximately 8 years
Secondary outcome [4] 0 0
Stage 2: Change from baseline in patient-reported outcomes measurement information system (PROMIS) profile domains(adult and pediatric (6-17 years of age) participants)
Timepoint [4] 0 0
Up to approximately 8 years
Secondary outcome [5] 0 0
Stage 2: Change from baseline in investigator global impression of change (IGIC) scale (adult and pediatric (6-17 years of age) participants)
Timepoint [5] 0 0
Up to approximately 8 years
Secondary outcome [6] 0 0
Stage 2: Change from baseline in health utilities of the EuroQol 5-dimension (EQ-5D) (adult and pediatric (6-17 years of age) participants)
Timepoint [6] 0 0
Up to approximately 8 years
Secondary outcome [7] 0 0
Duration of response (DOR) in adult and pediatric participants who receive alpelisib (Stage 1 and 2)
Timepoint [7] 0 0
Up to approximately 8 years
Secondary outcome [8] 0 0
Radiological response rate of alpelisib in adult and pediatric (6-17 years of age) participants (Stage 1)
Timepoint [8] 0 0
Baseline, Week 24
Secondary outcome [9] 0 0
Radiological response rate of alpelisib in adult and pediatric participants (Stage 1 and 2)
Timepoint [9] 0 0
Up to approximately 8 years
Secondary outcome [10] 0 0
Alpelisib plasma concentrations (Stage 1 and 2)
Timepoint [10] 0 0
On Day 1 of Week 8, 16, 24, 48 and 120
Secondary outcome [11] 0 0
Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants at Week 24 (Stage 1 and 2)
Timepoint [11] 0 0
Week 24
Secondary outcome [12] 0 0
Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants (Stage 1 and 2)
Timepoint [12] 0 0
Up to approximately 8 years
Secondary outcome [13] 0 0
Change from baseline in LyM lesions in adult and pediatric participants at Week 24 (Stage 1 and 2)
Timepoint [13] 0 0
Baseline, Week 24
Secondary outcome [14] 0 0
Change from baseline in LyM lesions in adult and pediatric participants (Stage 1 and 2)
Timepoint [14] 0 0
Up to approximately 8 years
Secondary outcome [15] 0 0
Percentage of participants with changes in non-target lesions in adult and pediatric participants at Week 24 (Stage 1 and 2)
Timepoint [15] 0 0
Baseline, Week 24
Secondary outcome [16] 0 0
Percentage of participants with changes in non-target lesions in adult and pediatric participants (Stage 1 and 2)
Timepoint [16] 0 0
Up to approximately 8 years
Secondary outcome [17] 0 0
Percentage of participants with new lesions in adult and pediatric participants at Week 24 (Stage 1 and 2)
Timepoint [17] 0 0
Baseline, Week 24
Secondary outcome [18] 0 0
Percentage of participants with new lesions in adult and pediatric participants (Stage 1 and 2)
Timepoint [18] 0 0
Up to approximately 8 years

Eligibility
Key inclusion criteria
Key

* 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 LyM at the time of informed consent
* Participant is not considered as a candidate for or is not willing to receive local therapy options 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
* Participant has at least one measurable LyM lesion confirmed by BIRC assessment prior to randomization.

Key
Minimum age
2 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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.

Other inclusion/exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/11/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
5/05/2030
Actual
Sample size
Target
230
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Novartis Investigative Site - Brisbane
Recruitment postcode(s) [1] 0 0
4101 - Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington
Country [7] 0 0
Belgium
State/province [7] 0 0
Bruxelles
Country [8] 0 0
France
State/province [8] 0 0
Bordeaux Cedex
Country [9] 0 0
France
State/province [9] 0 0
Bron Cedex
Country [10] 0 0
France
State/province [10] 0 0
Caen
Country [11] 0 0
France
State/province [11] 0 0
Lille
Country [12] 0 0
France
State/province [12] 0 0
Marseille
Country [13] 0 0
France
State/province [13] 0 0
Montpellier
Country [14] 0 0
France
State/province [14] 0 0
Paris cedex 10
Country [15] 0 0
France
State/province [15] 0 0
Tours 9
Country [16] 0 0
Germany
State/province [16] 0 0
Baden Wuerttemberg
Country [17] 0 0
Germany
State/province [17] 0 0
Freiburg
Country [18] 0 0
Germany
State/province [18] 0 0
Koeln
Country [19] 0 0
Germany
State/province [19] 0 0
Leipzig
Country [20] 0 0
Italy
State/province [20] 0 0
BO
Country [21] 0 0
Italy
State/province [21] 0 0
MI
Country [22] 0 0
Italy
State/province [22] 0 0
RM
Country [23] 0 0
Italy
State/province [23] 0 0
Napoli
Country [24] 0 0
Spain
State/province [24] 0 0
Barcelona
Country [25] 0 0
Spain
State/province [25] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
novartis.email@novartis.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05948943