Clinical Trials Register

Summary
EudraCT Number:	2020-003415-98
Sponsor's Protocol Code Number:	INCB50465-304
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-05-20
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

2020-003415-98

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled Study of the PI3Kd Inhibitor Parsaclisib Plus Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib

Studio randomizzato, in doppio cieco, controllato verso placebo sull’inibitore di PI3Kd parsaclisib più ruxolitinib in partecipanti affetti da mielofibrosi con risposta subottimale a ruxolitinib

A.3.1

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

A phase 3 study of parsaclisib plus ruxolitinib in patients with myelofibrosis

Uno studio di fase 3 con parsaclisib più ruxolitinib in pazienti con mielofibrosi

A.3.2

Name or abbreviated title of the trial where available

INCB50465-304

A.4.1

Sponsor's protocol code number

INCB50465-304

A.5.4

Other Identifiers

Name:

IND number

Number:

147,207

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	INCYTE CORPORATION
B.1.3.4	Country	United States
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	Incyte Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Incyte Corporation
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	1801 Augustine Cut-Off
B.5.3.2	Town/ city	Wilmington
B.5.3.3	Post code	DE 19803
B.5.3.4	Country	United States
B.5.4	Telephone number	+13024986700
B.5.5	Fax number	+13024252734
B.5.6	E-mail	RA@incyte.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	parsaclisib
D.3.2	Product code	[INCB050465]
D.3.4	Pharmaceutical form	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	parsaclisib
D.3.9.1	CAS number	1426698-88-5
D.3.9.2	Current sponsor code	INCB050465
D.3.9.3	Other descriptive name	PARSACLISIB HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB193469
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5000
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	parsaclisib
D.3.2	Product code	[INCB050465]
D.3.4	Pharmaceutical form	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	parsaclisib
D.3.9.1	CAS number	1426698-88-5
D.3.9.2	Current sponsor code	INCB050465
D.3.9.3	Other descriptive name	PARSACLISIB HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB193469
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2500
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	parsaclisib
D.3.2	Product code	[INCB050465]
D.3.4	Pharmaceutical form	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	parsaclisib
D.3.9.1	CAS number	1426698-88-5
D.3.9.2	Current sponsor code	INCB050465
D.3.9.3	Other descriptive name	PARSACLISIB HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB193469
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
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	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	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	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

myelofibrosis

mielofibrosi

E.1.1.1

Medical condition in easily understood language

myelofibrosis

mielofibrosi

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10028537
E.1.2	Term	Myelofibrosis
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 evaluate and compare the efficacy of parsaclisib plus ruxolitinib versus placebo plus ruxolitinib on spleen volume at Week 24.

Valutare e confrontare l’efficacia di parsaclisib più ruxolitinib rispetto a placebo più ruxolitinib sul volume della milza alla Settimana 24

E.2.2

Secondary objectives of the trial

* To evaluate and compare the effect of parsaclisib plus ruxolitinib versus placebo plus ruxolitinib on participant reports of MF symptoms.
* To evaluate and compare the effect of parsaclisib plus ruxolitinib versus placebo plus ruxolitinib with respect to OS.
* To evaluate and compare the safety and tolerability of parsaclisib plus ruxolitinib versus placebo plus ruxolitinib

* Valutare e confrontare l’effetto di parsaclisib più ruxolitinib rispetto a placebo più ruxolitinib sui sintomi di MF riferiti dai partecipanti.
* Valutare e confrontare l’effetto di parsaclisib più ruxolitinib rispetto a placebo più ruxolitinib in termini di OS.
* Valutare e confrontare la sicurezza e la tollerabilità di parsaclisib più ruxolitinib rispetto a placebo più ruxolitinib.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Men and women aged 18 years or older;
2. Diagnosis of PMF, PPV-MF, or PET-MF;
3. DIPSS risk category of intermediate-1, intermediate-2, or high;
4. Treated with ruxolitinib for = 3 months with a stable dose for at least the last 8 weeks prior to Day 1;
5. Evidence of suboptimal response to ruxolitinib
For the complete list of inclusion criteria please refer to the protocol, section 5.1

1. Uomini e donne di età pari o superiore a 18 anni;
2. Diagnosi di PMF, PPV-MF o PET-MF;
3. Categoria di rischio DIPSS intermedio-1, intermedio-2 o alto;
4. Trattato con ruxolitinib per = 3 mesi con una dose stabile per almeno le ultime 8 settimane prima del giorno 1;
5. Evidenza di una risposta non ottimale a ruxolitinib
Per l'elenco completo dei criteri di inclusione, fare riferimento al protocollo, sezione 5.1

E.4

Principal exclusion criteria

1. Prior therapy with any drug that inhibits PI3K;
2. Use of experimental drug therapy for MF or any other standard drug used for MF (e.g., danazol, hydroxyurea) with the exception of ruxolitinib, within 3 months of starting study drug, and/or lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better.
3. Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
4. Recent history of inadequate bone marrow reserve.
For the complete list of exclusion criteria please refer to the protocol,
section 5.2

1. Terapia precedente con qualsiasi farmaco che inibisce PI3K;
2. Uso della terapia farmacologica sperimentale per la MF o di qualsiasi altro farmaco standard usato per la MF (ad es. Danazolo, idrossiurea) ad eccezione di ruxolitinib, entro 3 mesi dall'inizio del farmaco in studio e / o mancanza di recupero da tutte le tossicità dalla terapia precedente (eccetto ruxolitinib) al Grado 1 o migliore.
3. Incapacità di deglutire il cibo o qualsiasi condizione del tratto gastrointestinale superiore che precluda la somministrazione di farmaci per via orale.
4. Storia recente di riserva di midollo osseo inadeguata.
Per l'elenco completo dei criteri di esclusione fare riferimento al protocollo,
sezione 5.2

E.5 End points

E.5.1

Primary end point(s)

Proportion of participants achieving >= 25% reduction in spleen volume from baseline to Week 24 as measured by MRI (or CT scan in applicable participants).

Percentuale di partecipanti che ottengono una riduzione >=25% del volume della milza dal basale alla Settimana 24 misurata mediante RM (o TAC laddove pertinente).

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24

Settimana 24

E.5.2

Secondary end point(s)

* Proportion of participants who have a >= 50% reduction in TSS from baseline to Week 24 as measured by the MFSAF v4.0 diary
* Change in TSS from baseline to Week 24 as measured by the MFSAF v4.0 diary.
* Time to the first >= 50% reduction in TSS as measured by the MFSAF v4.0 diary
* OS determined from the date of randomization until death due to any cause.
* Safety and tolerability

Percentuale di partecipanti che presentano una riduzione =50% dal basale alla Settimana 24 misurata dal diario MFSAF v4.0.
Cambiamento nel TSS dal basale alla Settimana 24 misurato dal diario MFSAF v4.0.
Tempo alla prima riduzione >=50% nel TSS misurato dal diario MFSAF v4.0.
L’OS sarà determinata dalla data di randomizzazione fino alla data di decesso per qualunque causa.
La sicurezza e la tollerabilità saranno valutate mediante monitoraggio della frequenza e della gravità degli AE, eseguendo esami obiettivi e valutando i cambiamenti nei parametri vitali, negli ECG e nei risultati di laboratorio.

E.5.2.1

Timepoint(s) of evaluation of this end point

* Proportion of participants with >= 50% reduction in TSS: week 24
* Change in TSS: week 24
* Time to the first >= 50% reduction in TSS:
* OS: throughout the study
* Safety and tolerability: throughout the study

* Proporzione di partecipanti con riduzione = 50% del TSS: settimana 24
* Modifica del TSS: settimana 24
* Tempo alla prima riduzione >= 50% del TSS:
* OS: durante lo studio
* Sicurezza e tollerabilità: durante tutto lo studio

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

Australia

Canada

China

Japan

United States

Austria

Belgium

Finland

France

Germany

Hungary

Ireland

Italy

Norway

Poland

Spain

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

LVLS

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

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)

F.1.1.6

Adolescents (12-17 years)

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:

136

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

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

F.4.2.2

In the whole clinical trial

212

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)

After 24 weeks, participants will enter the extension period of the study. Treatment will continue as long as it is tolerated and the participant does not meet discontinuation criteria.
Participants randomized to placebo will have the opportunity to crossover to receive parsaclisib (with continued ruxolitinib) once they have reached Week 24. Crossover participants may also continue as long as the regimen is tolerated and they do not meet discontinuation criteria.

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

2021-03-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-03-16

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-03-03

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