Clinical Trials Register

Summary
EudraCT Number:	2013-003583-31
Sponsor's Protocol Code Number:	CINC424B2401
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-12-13
Trial results	View 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

Spain - AEMPS

A.2

EudraCT number

2013-003583-31

A.3

Full title of the trial

Randomized, open label, multicenter phase IIIb study evaluating the efficacy and safety of ruxolitinib versus best available therapy in patients with polycythemia vera who are hydroxyurea resistant or intolerant (Response 2)

Estudio fase IIIb, multicéntrico, abierto, aleatorizado que evalúa la eficacia y la seguridad de ruxolitinib frente a la mejor terapia disponible en pacientes con policitemia vera que presentan intolerancia o resistencia a hidroxiurea (Response 2)

A.3.1

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

Ruxolitinib efficacy and safety in patients with HU resistant or intolerant polycythemia vera vs best available therapy

Eficacia y seguridad de ruxolitinib en pacientes con policitemia vera resistentes o intolerantes a hidroxiurea frente a la mejor terapia disponible (Response 2)

A.3.2

Name or abbreviated title of the trial where available

Response 2

A.4.1

Sponsor's protocol code number

CINC424B2401

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	Novartis Farmacéutica, S.A.
B.1.3.4	Country	Spain
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 Services 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 Farmacéutica, S.A.
B.5.2	Functional name of contact point	Departamento Médico Oncología (GMO)
B.5.3	Address:
B.5.3.1	Street Address	Gran Vía de les Corts Catalanes, 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	34900353036
B.5.5	Fax number	34932479903
B.5.6	E-mail	eecc.novartis@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	Yes
D.2.1.1.1	Trade name	Jakavi
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Ruxolitinib
D.3.2	Product code	INC424
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	Ruxolitinib
D.3.9.1	CAS number	1092939-17-7
D.3.9.2	Current sponsor code	INC424
D.3.9.3	Other descriptive name	RUXOLITINIB PHOSPHATE
D.3.9.4	EV Substance Code	SUB32897
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	5
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Polycythemia vera resistant or intolerant to hydroxyurea

Policitemia vera que presentan intolerancia o resistencia a hidroxiurea

E.1.1.1

Medical condition in easily understood language

Polycythemia vera

Policitemia vera

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	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10036061
E.1.2	Term	Polycythemia vera
E.1.2	System Organ Class	100000004864

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

efficacy of ruxolitinib to BAT as assessed by Hct control at Week 28

Comparar la eficacia de ruxolitinib con BAT, evaluado con control del valor de
hematocrito (Hct) en la Semana 28.

E.2.2

Secondary objectives of the trial

Key secondary:
1. efficacy of ruxolitinib to BAT as assessed by peripheral blood count remission at Week 28

Other secondary:
2. efficacy of ruxolitinib to BAT as assessed by durable Hct control at Week 52
3. efficacy of ruxolitinib to BAT as assessed by durable peripheral blood count remission at Week 52
4. change in ECOG status
5. change in spleen length
6. efficacy of ruxolitinib to BAT as assessed by partial remission based on the ELN and IWG-MRT criteria at Week 28
7. efficacy of ruxolitinib to BAT as assessed by durable partial remission based on the ELN and IWG-MRT criteria at Week 52
8. efficacy of BAT patients after they cross over to ruxolitinib
9. changes in MPN-SAF TSS
10. resolution of disease related symptoms in MPN-SAF TSS at Week 28
11. changes in patient reported outcomes
12. safety of ruxolitinib and Best Available Therapy
13. safety of BAT patients after they cross over

>Comp. la efic. de ruxolitinib con BAT, eva. como remisión hematológica en sangre periférica (em. 28)
>Comp. eficacia de ruxolitinib con BAT, eva. con el control dura. de Hct en la sem. 52
>Comp. efic. de ruxolitinib con BAT, eva. con la remisión dura. del recuento hemático periférico en la sem. 52
>Eva. el camb. en el ECOG
>Eva. el camb. en el volumen del bazo
>Comp. eficacia de ruxolitinib con BAT, con la remisión parcial basado en los criterios del IWG-MRT y de la ELN en sem. 28
>Comp. eficacia de ruxolitinib con BAT, eva. con la remisi. parcial basado en los criterios IWG-MRT y de la ELN en sem. 52
>Eva. la efic. de BAT después del cruce a ruxolitinib.
>Eva. los camb. en MPN-SAF TSS comp. ruxolitinib con BAT
>Eva. la resolución de los sínt. relacionados con la enferm. en MPNSAF TSS comp. ruxolitinib con BAT en sem. 28
>Eva. los camb. en los result. notificados por el paciente
>Eva. la segur. de ruxolitinib y BAT >Eva. la segur. de BAT después del cruce a ruxolitinib.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Confirmed diagnosis of PV according to the 2008 World Health Organization criteria
- Non-palpable spleen
- Phlebotomy dependent, Resistant to or intolerant of hydroxyurea
- ECOG performance status of 0, 1 or 2.

Other inclusion criteria as defined by protocol may apply

>Diagnóstico confirmado de PV según los criterios revisados de la OMS.
>Bazo no palpable.
>Un Hct entre 40 y 45% inclusive, dentro de los 14 días de la visita basal y de la necesidad de flebotomía.
>Resistencia o intolerancia a hidroxiurea
>Estado del ECOG de menor o igual a 2.

E.4

Principal exclusion criteria

- Inadequate liver or renal function
- Significant bacterial, fungal, parasitic, or viral infection requiring treatment
- Active malignancy within the past 5 years, excluding specific skin cancers
- Previously received treatment with a JAK inhibitor
- Being treated with any investigational agent
- Women who are pregnant or nursing.

Other exclusion criteria as defined by protocol may apply.

>Función renal o hepática inadecuada.
>Infección vírica, parasitaria, fúngica o bacteriana significativa que precise
tratamiento.
>Enfermedad maligna activa dentro de los 5 últimos años, excluyendo cánceres cutáneos específicos y neoplasia intraepitelial cervical.
>Evento tromboembólicos dentro de los últimos 6 meses.
>Tratamiento recibido previamente con un inhibidor de JAK.
>Mujeres embarazadas o en periodo de lactancia.

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients achieving Hct control at Week 28 as defined by:
-Hct < 45% at Week 16 and maintained until Week 28, and
-No phlebotomy from Week 4 to Week 28, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit.

Porcentaje de pacientes que alcancen control del Hct en la semana 28, definido con:
-Hct < 45% en la semana 16 y mantenido hasta la semana 28, y
-Sin necesidad de flebotomía desde la semana 4 a la semana 28, con no más de una flebotomía que ocurra después de la aleatorización y antes de la visita de la semana 4.

E.5.1.1

Timepoint(s) of evaluation of this end point

week 28

Semana 28

E.5.2

Secondary end point(s)

1. Proportion of patients achieving a peripheral blood count remission at Week 28 as defined by:
-Hct < 45% at Week 16 and maintained until Week 28, and
-WBC < 10 x109/L at Week 16 and maintained until Week 28, and
-Platelets iqual or less than 400 x 109/L at Week 16 and maintained until Week 28, and
-No phlebotomy from Week 4 to Week 28, with no more than one phlebotomy occurring post randomization and prior to the Week 4 visit.

Porcentaje de pacientes que alcancen una remisión de recuento hemático periférico en la semana 28 definido con:
-Hct < 45% en la Semana 16 y que se mantenga en la semana 28, y
-WBC < 10 x109/L en la semana 16 y que se mantenga hasta la semana 28, y
-Plaquetas igual o menor a 400 x 109/L en la semana 16 y que se mantenga hasta la semana 28, y
-Sin necesidad de flebotomía desde la semana 4 a la semana 28, con no más de una flebotomía que ocurra después de la aleatorización y antes de la visita de la semana 4.

E.5.2.1

Timepoint(s) of evaluation of this end point

For key secondary,
1. week 28

Secundaria principal:
semana 28

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

Yes

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

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

document medical resource utilization (MRU)

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Mejor terapia disponible (BAT)

Best available therapy (BAT)

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

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

Belgium

Canada

France

Israel

Italy

Switzerland

Turkey

Australia

Germany

Hungary

India

Korea, Republic of

Spain

E.8.7

Trial has a data monitoring committee

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

Last Patient Last Visit defined as after all patients have either discontinued or completed the Week 52 visit or the applicable cross-over visit plus the 30 day follow up visit

Última visita del último paciente, definido como después de que todos los pacientes que hayan discontinuado o completado la visita de la semana 52 o la visita de cruce correspondiente, más el día 30 de la visita de seguimiento.

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

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:

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

104

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)

Following the last visit, patients who are still receiving benefit in the opinion of the investigator may continue to receive ruxolitinib. Patients will be transitioned to a local supply of ruxolitinib, off study, which will be reimbursed by Novartis where necessary. If local supply is not available to a patient at that time, s/he may be able to receive ruxolitinib under a separate protocol if approved by the country regulatory authority.

Después de la última visita, los pacientes que todavía están recibiendo beneficios en opinión del investigador, podrán continuar recibiendo ruxolitinib. Los pacientes recibirán medicación local de ruxolitinib, que será reembolsado por Novartis en caso necesario. Si la medicación local no está disponible para un paciente en ese momento, el paciente podrá recibir ruxolitinib bajo un protocolo separado si es aprobado por la autoridad reguladora nacional.

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

2014-01-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-01-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-04-07

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