Clinical Trials Register

Summary
EudraCT Number:	2020-000561-16
Sponsor's Protocol Code Number:	CBYL719F12201
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-04
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-000561-16

A.3

Full title of the trial

EPIK-P2: A Phase II double-blind study with an upfront, 16- week randomized, placebo-controlled period, to assess the efficacy, safety and pharmacokinetics of alpelisib (BYL719) in pediatric and adult patients with PIK3CA-related overgrowth spectrum (PROS)

EPIK-P2: Studio di Fase II, in doppio cieco, con un periodo iniziale randomizzato di 16 settimane, controllato versus placebo, per valutare l’efficacia, la sicurezza d’impiego e la farmacocinetica di alpelisib (BYL719) in pazienti pediatrici e adulti con sindromi da iperaccrescimento PIK3CA-correlate (PROS)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

This is a research study to find out if the study treatment alpelisib (BYL719) is safe and can help others who have confirmed diagnosis of PIK3CA-related overgrowth spectrum (PROS)

Questo è uno studio di ricerca per scoprire se il trattamento di studio alpelisib (BYL719) è sicuro e può aiutare altri che hanno confermato la diagnosi di spettro di iperaccrescimento PIK3CA-correlate (PROS)

A.3.2

Name or abbreviated title of the trial where available

EPIK-P2

A.4.1

Sponsor's protocol code number

CBYL719F12201

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/329/2020

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	NOVARTIS PHARMA AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Farma S.p.A.
B.5.2	Functional name of contact point	Drug Regulatotory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Largo umberto Boccioni, 1
B.5.3.2	Town/ city	Origgio (VA)
B.5.3.3	Post code	21040
B.5.3.4	Country	Italy
B.5.4	Telephone number	0296541
B.5.5	Fax number	029659066
B.5.6	E-mail	info.studiclinici@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Alpelisib
D.3.2	Product code	[BYL719 dark yellow]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALPELISIB
D.3.9.1	CAS number	1217486-61-7
D.3.9.2	Current sponsor code	BYL719
D.3.9.4	EV Substance Code	SUB180707
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	alpelisib
D.3.2	Product code	[BYL719 pale yellow]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALPELISIB
D.3.9.1	CAS number	1217486-61-7
D.3.9.2	Current sponsor code	BYL719
D.3.9.4	EV Substance Code	SUB180707
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	alpelisib
D.3.2	Product code	[BYL719 dark yellow]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALPELISIB
D.3.9.1	CAS number	1217486-61-7
D.3.9.2	Current sponsor code	BYL719
D.3.9.4	EV Substance Code	SUB180707
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	125
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

PIK3CA-related overgrowth spectrum (PROS)

Sindromi da iperaccrescimento PIK3CA-correlate (PROS)

E.1.1.1

Medical condition in easily understood language

PROS is a group of so-called overgrowth syndromes caused by changes in functioning of PI3K pathway

PROS è un gruppo di sindromi di crescita eccessiva causate da cambiamenti nel funzionamento del percorso PI3K

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	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10010331
E.1.2	Term	Congenital, familial and genetic disorders
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

To demonstrate the efficacy of alpelisib as measured by the proportion of participants randomized to alpelisib with a response at Week 24 in at least one of the following
groups:
- Group 1 (>= 18 yr-old)
- Group 2 (6 - 17 yr-old)
In children/adolescents aged between 6 and 17 years (in Group 2) and adults (Group 1: >= 18 years) with PROS, the question of primary scientific interest is to evaluate the benefit of alpelisib with regard to the percentage of responder at week 24, considering participants who will stop treatment before week 24 and participants who will undergo surgery as a rescue therapy for any PROS injury as non responder.

Dimostrare l’efficacia di alpelisib misurata dalla percentuale dei partecipanti randomizzati ad alpelisib con una risposta alla settimana 24 in almeno uno dei seguenti gruppi:
• Gruppo 1 (>= 18 anni)
• Gruppo 2 (6-17 anni)
Nei bambini/adolescenti di età compresa tra 6 e 17 anni (nel Gruppo 2) e negli adulti (Gruppo 1: = 18 anni) con PROS, il quesito di interesse scientifico primario è valutare il beneficio di alpelisib riguardo alla percentuale di responder alla settimana 24, considerando i partecipanti che sospenderanno il trattamento prima della settimana 24 e i partecipanti che saranno sottoposti a intervento chirurgico come terapia rescue per qualsiasi lesione PROS come non responder.

E.2.2

Secondary objectives of the trial

- To demonstrate the efficacy of alpelisib vs placebo based on the comparison of the proportion of participants with response at Week 16 in Group 1 or Group 2
- To assess safety and tolerability of alpelisib as compared to placebo in Groups 1 and 2 up to week 16
- To assess the overall safety and tolerability of alpelisib in participants with PROS over time
- To assess changes in patient-reported pain intensity and overall severity of symptoms at Week 16 on treatment with alpelisib as compared to placebo in pediatric and adult populations
- To assess changes in target and non-target lesions over time and appearance of new lesions on treatment from baseline over time
- To assess the PK of alpelisib in adult and pediatric patients with PROS

For other secondary objectives see the protocl

-Dimostrare l’efficacia di alpelisib in confronto a placebo sulla base del confronto della percentuale di partecipanti con risposta alla settimana 16 nel Gruppo 1 o nel Gruppo 2
-Valutare la sicurezza d’impiego e la tollerabilità di alpelisib in confronto a placebo nei Gruppi 1 e 2 fino alla settimana 16.
Valutare la sicurezza globale e la tollerabilità di alpelisib nei partecipanti con PROS nel corso del tempo.
• Valutare le modifiche dell’intensità del dolore riportato dal paziente e della gravità complessiva dei sintomi alla settimana 16 durante il trattamento con alpelisib in confronto a placebo nelle popolazioni pediatrica e adulta.
• Valutare le modifiche delle lesioni target e non-target nel corso del tempo e la comparsa di nuove lesioni durante il trattamento, rispetto al basale, nel corso del tempo.
• Valutare la farmacocinetica di alpelisib nei pazienti adulti e pediatrici con PROS.

Per altri obiettivi secondari si veda il protocollo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent and assent (when applicable) from the patient, parent, or guardian prior to any study related screening procedures are performed
2. Patients with diagnosis of PROS with symptomatic and /or progressive overgrowth and at least one measurable PROS-related lesion confirmed by blinded independent review committee (BIRC) assessment
3. Documented evidence of a somatic mutation(s) in the PIK3CA gene performed in local laboratories
4. A tissue sample must be available to be sent to a Novartis-designated central laboratory
5. Karnofsky (in patients > 16 years old at study entry)/Lansky (=16 yrs of age at study entry) performance status index =50 within 7 days before study treatment start
6. Adequate bone marrow and organ function including Fasting plasma glucose (FPG) = 140 mg/dL (7.7 mmol/L)* and Glycosylated hemoglobin (HbA1c) = 6.5% (both criteria have to be met) (as assessed by central laboratory for eligibility within 7 days before study treatment start)
7. Presence of at least one PROS-related measurable lesion defined as a lesion with longest diameter =2 cm, when the volume can be accurately
and reproducibly measured by MRI, and associated with complaints, clinical symptoms or functional limitations affecting the patient's everyday life. Measurability must be confirmed by BIRC before randomization..

1. Firmato il consenso informato e il consenso informato (se del caso) del paziente, del genitore o del tutore prima dell'esecuzione di qualsiasi procedura di screening relativa allo studio
2.Pazienti con diagnosi di PROS con crescita eccessiva sintomatica e/o progressiva e almeno una lesione misurabile correlata al PROS confermata da una valutazione in cieco del comitato di revisione indipendente (BIRC).
3. Prove documentate di una o più mutazioni somatiche nel gene PIK3CA eseguite in laboratori locali
4. Un campione di tessuto deve essere disponibile per essere inviato ad un laboratorio centrale designato da Novartis
5. Karnofsky (in pazienti > 16 anni all'ingresso dello studio)/Lansky (=16 anni di età all'ingresso dello studio) indice di performance status =50 entro 7 giorni prima dell'inizio del trattamento di studio
6. Adeguata funzione del midollo osseo e degli organi, compreso il glucosio plasmatico a digiuno (FPG) = 140 mg/dL (7,7 mmol/L)* e l'emoglobina glicosilata (HbA1c) = 6,5% (entrambi i criteri devono essere soddisfatti) (come valutato dal laboratorio centrale per l'idoneità entro 7 giorni prima dell'inizio del trattamento di studio)
7. Presenza di almeno una lesione misurabile correlata alla PROS definita come lesione con diametro più lungo = 2 cm, quando il volume può essere misurato in modo accurato e riproducibile dalla risonanza magnetica, e associati a disturbi, sintomi clinici o limitazioni funzionali che influenzano la vita quotidiana del paziente. La misurabilità deve essere confermata da BIRC prima dellarandomizzazione .

E.4

Principal exclusion criteria

1. Participant with only isolated macrodactyly, skin nevus/nevi and macroencephaly (the only clinical feature or a combination of any of three of them), in absence of other PROS-related lesions at the time of informed consent
2. Previous treatment with alpelisib and/or any other PI3K inhibitor(s) (except treatment attempt, defined as the attempt to treat PROS with any of PI3K inhibitors, with treatment duration less than 2 weeks and stopped at least 4 weeks prior to the first dose of study medication with alpelisib)
3. Radiation exposure for PROS treatment purpose within the previous 12 months on those PROS areas which are expected to qualify for target lesions (except lesion(s) progressing after completion of radiotherapy) at time of informed consent.
4. Debulking or other major surgery performed within 3 months at time of informed consent
5. Clinically meaningful PROS-related thrombotic event (Grade 2 and more as per CTCAE v.4.03) within 30 days before informed consent, and/or sclerotherapy/embolization for vascular complications performed within 6 weeks before informed consent. Participants (receiving anticoagulants for PROS related coagulopathy, primary or secondary prophylaxis of thrombosis may be included in the study)
6. Participants with documented pneumonitis or interstitial lung disease at time of informed consent
7. History of acute pancreatitis within 1 year before informed consent or past medical history of chronic pancreatitis at time of informed consent
8. Participants with an established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus at time of informed consent
9. Known history of seizure, or epilepsy, regardless of relatedness to PROS sprectrum at time of informed consent, when epilepsy is not controlled and/or the patient may not be switched to non-enzyme inducing antiepilectic drug(s) at time of informed consent.

1. Partecipante con sola macrodattilia isolata, nevo cutaneo/nevi e macroencefalia (l'unica caratteristica clinica o una combinazione di tre di esse), in assenza di altre lesioni correlate alla PROS al momento del consenso informato
2. Precedente trattamento con alpelisib e/o qualsiasi altro inibitore PI3K (eccetto il tentativo di trattamento, definito come il tentativo di trattare il PROS con uno qualsiasi degli inibitori PI3K, con durata del trattamento inferiore a 2 settimane e interrotto almeno 4 settimane prima della prima dose di farmaco di studio con alpelisib)
3.Esposizione alle radiazioni ai fini del trattamento PROS nei 12 mesi precedenti su quelle aree PROS che si ritiene possano essere qualificate per le lesioni target (ad eccezione delle lesioni che progrediscono dopo il completamento della radioterapia) al momento del consenso informato.
4. Debulking o altri interventi chirurgici importanti eseguiti entro 3 mesi al momento del consenso informato
5. Evento trombotico clinicamente significativo relativo al PROS (Grado 2 e più secondo CTCAE v.4.03) entro 30 giorni prima del consenso informato e/o scleroterapia/embolizzazione per complicanze vascolari eseguita entro 6 settimane prima del consenso informato. I partecipanti (che ricevono anticoagulanti per coagulopatia correlata alla PROS, profilassi primaria o secondaria della trombosi possono essere inclusi nello studio)
6.Partecipanti con polmonite o malattia polmonare interstiziale documentata al momento del consenso informato
7.Storia di pancreatite acuta entro 1 anno prima del consenso informato o storia medica passata di pancreatite cronica al momento del consenso informato
8. Partecipanti con una diagnosi accertata di diabete mellito di tipo I o diabete mellito di tipo II non controllato al momento del consenso informato
9.Anamnesi nota di crisi epilettiche, o epilessia, indipendentemente dalla correlazione con lo spettro PROS al momento del consenso informato, quando l'epilessia non è controllata e/o il paziente non può essere passato a farmaci antiepilettici non indotti da enzimi al momento del consenso informato.

E.5 End points

E.5.1

Primary end point(s)

Response defined by achieving at least 20% reduction from baseline in the sum of target lesion volumes (1 to 3 lesions, assessed by MRI by ablinded independent review committee (BIRC)) at Week 24, provided that none of the individual target lesions has = 20% increase from baseline and in absence of progression of non-target lesions and without new lesions.

Risposta definita ottenendo una riduzione di almeno il 20% rispetto alla linea di base nella somma dei volumi di lesioni target (da 1 a 3 lesioni, valutate dalla risonanza magnetica da un comitato di revisione indipendente cieco (BIRC)) alla 24a settimana, a condizione che nessuna delle singole lesioni target abbia un aumento del 20% rispetto alla linea di base e in assenza di progressione di lesioni non target e senza nuove lesioni.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24

Settimana 24

E.5.2

Secondary end point(s)

Response defined by achieving at least 20% reduction from baseline in the sum of target lesion volumes (1 to 3 lesions, assessed by MRI by a blinded independent review committee (BIRC)) at Week 16, provided that none of the individual target lesions has = 20% increase from baseline and in absence of progression of non-target lesions and without new lesions.

Risposta definita ottenendo una riduzione di almeno il 20% rispetto alla linea di base nella somma dei volumi di lesioni target (da 1 a 3 lesioni, valutate dalla RMN da un comitato di revisione indipendente cieco (BIRC)) alla sedicesima settimana, a condizione che nessuna delle singole lesioni target abbia un aumento del 20% rispetto alla linea di base e in assenza di progressione di lesioni non target e senza nuove lesioni.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 16

Settimana 16

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Information not present in EudraCT

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

Canada

Hong Kong

Korea, Democratic People's Republic of

Turkey

United States

France

Germany

Italy

Netherlands

Norway

Spain

Switzerland

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

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

End of the trial is defined as when the last participant, regardless of study period, finishes their study Completion visit and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator or, in the event of an early study termination decision, the date of that decision.

La fine dello studio è definita come il momento in cui l'ultimo partecipante, indipendentemente dal periodo di studio, termina la sua visita di completamento dello studio e le valutazioni ripetute associate a questa visita sono state documentate e seguite in modo appropriato dallo sperimentatore o, in caso di decisione di conclusione anticipata dello studio, la data di tale decisione.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

As the study includes paediatric patients, the parents' or guardians' consent will be required. In these cases, the participant should be informed about the study to the extent possible given his/her understanding.

Poiché lo studio include pazienti pediatrici, sarà richiesto il consenso dei genitori o dei tutori. In questi casi, il partecipante deve essere informato dello studio nella misura del possibile, data la sua comprensione.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In the whole clinical trial

150

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Participants who complete 5 years of treatment in the study and are still deriving clinical benefit from alpelisib based on the investigator's evaluation, may receive post-trial access. Post Trial Access (PTA) means the provision of treatment to study participants following their completion of study participation. Every effort will be made to continue provision of study treatment after 5 years of total duration of study treatment.

I partecipanti che completano 5 anni di trattamento nello studio e che continuano a trarre beneficio clinico da alpelisib in base alla valutazione dello sperimentatore, possono ricevere un accesso post-trial. Per accesso post-trial (PTA) si intende l'erogazione del trattamento ai partecipanti allo studio dopo il completamento della loro partecipazione allo studio. Si farà tutto il possibile per continuare a fornire il trattamento dopo 5 anni di durata totale dello studio.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-02-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-14

P. End of Trial
P.	End of Trial Status	Ongoing

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