Clinical Trials Register

Summary
EudraCT Number:	2013-000981-12
Sponsor's Protocol Code Number:	CICL670A2421
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:	2013-08-08
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

2013-000981-12

A.3

Full title of the trial

An open-label, phase II, randomized, pilot study to assess
the effect in term of erythroid improvement of deferasirox
combined with erythropoietin compared to erythropoietin
alone in patients with low- and int-1-risk myelodysplastic
syndrome.

Estudio piloto abierto, fase II, randomizado, para evaluar el efecto de deferasirox combinado con eritropoyetina comparado con eritropoyetina sola, en términos de mejoría eritroide, en pacientes con síndrome mielodisplásico de riesgo bajo e int-1.

A.3.1

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

Combination study of deferasirox and erythropoietin in patients with low- and int-1-risk
myelodysplastic syndrome.

Estudio de combinación de deferasirox y eritropoyetina en pacientes con síndrome mielodisplásico con riesgo bajo e int-1.

A.4.1

Sponsor's protocol code number

CICL670A2421

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 Via 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	Exjade
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	Exjade
D.3.2	Product code	ICL670
D.3.4	Pharmaceutical form	Dispersible 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	DEFERASIROX
D.3.9.1	CAS number	201530-41-8
D.3.9.2	Current sponsor code	ICL670
D.3.9.3	Other descriptive name	ICL670
D.3.9.4	EV Substance Code	SUB21981
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	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.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	Yes
D.2.1.1.1	Trade name	Exjade
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	Exjade
D.3.2	Product code	ICL670
D.3.4	Pharmaceutical form	Dispersible 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	DEFERASIROX
D.3.9.1	CAS number	201530-41-8
D.3.9.2	Current sponsor code	ICL670
D.3.9.3	Other descriptive name	ICL670
D.3.9.4	EV Substance Code	SUB21981
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	500
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.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	Yes
D.2.1.1.1	Trade name	EPREX
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG, S.A.
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	EPREX
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.9.1	CAS number	113427-24-0
D.3.9.2	Current sponsor code	EPOETIN ALFA
D.3.9.3	Other descriptive name	EPOETIN ALFA
D.3.9.4	EV Substance Code	SUB06575MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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: 4
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	EPREX
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG, S.A.
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	EPREX
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EPOETIN ALFA
D.3.9.1	CAS number	113427-24-0
D.3.9.2	Current sponsor code	EPOETIN ALFA
D.3.9.3	Other descriptive name	EPOETIN ALFA
D.3.9.4	EV Substance Code	SUB06575MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

low- and int-1-risk myelodysplastic syndrome

Síndrome mielodisplásico de bajo riesgo e int-1

E.1.1.1

Medical condition in easily understood language

myelodysplastic syndromes

Síndrome mielodisplásico

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10028534
E.1.2	Term	Myelodysplastic syndrome NOS
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

To assess the effect of treatment with deferasirox combined with erythropoietin vs.
erythropoietin alone on erythropoiesis after 12 weeks of treatment defined by hemoglobin levels

Evaluar el efecto del tratamiento con deferasirox combinado con eritropoyetina comparado con eritropoyetina sola en la eritropoyesis después de 12 semanas de tratamiento definido por los niveles de hemoglobina

E.2.2

Secondary objectives of the trial

Key secondary objective:
To assess the effect of treatment with deferasirox combined with erythropoietin on
hematologic improvement within 24 weeks of treatment in patients randomized to
combination therapy at baseline defined by hemoglobin, platelets and neutrophil levels

Other secondary objectives as per protocol may apply.

Evaluar el efecto del tratamiento con deferasirox combinado con eritropoyetina en la mejoría hematológica dentro de las 24 semanas posteriores al tratamiento en pacientes aleatorizados a la terapia combinada en la visita basal definida por los niveles de hemoglobina, plaquetas y neutrófilos

Para el resto de objetivos secundarios, consultar el protocolo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients with low- and Int-1-risk myelodysplastic syndrome
? Documented diagnosis of the following:
? Myelodysplastic syndrome lasting ? 3 months and < 2 years
? Disease must not be secondary to treatment with radiotherapy, chemotherapy,
and/or immunotherapy for malignant or autoimmune diseases
? A hemoglobin < 10 g/dL and > 6 g/dL (no RBC transfusions are allowed during
study)
? History of transfusions < 10 RBC units
? 300 ng/mL < serum ferritin < 1,000 ng/mL
? Endogenous erythropoietin levels < 500 units/L

?Pacientes con síndrome mielodisplásico de riesgo bajo e int-1
?Diagnóstico documentado de lo siguiente:
?Síndrome mielodisplásico que dura ? 3 meses y < 2 años
?La enfermedad no ha de ser secundaria a tratamiento con radioterapia, quimioterapia y/o inmunoterapia para enfermedades malignas o autoinmunitarias
?Hemoglobina < 10 g/dl y > 6 g/dl (no se permiten transfusiones de RBC durante el estudio)
?Antecedente de transfusiones < 10 unidades de RBC
?300 ng/ml < ferritina sérica < 1.000 ng/ml
?Niveles de eritropoyetina endógena < 500 unidades/l

E.4

Principal exclusion criteria

? Patients with MDS with isolated del(5q)
? Patients who had received prior EPO treatment or other recombinant growth factors
regardless of the outcome (Patient who had received prior EPO treatment or other
recombinant growth factors for less than 4 weeks and not within 3 months before
screening without a documented response are allowed)
? Patients receiving steroids or immunosuppressive therapy for the improvement of
hematological parameters (prophylactic hydrocortisone to prevent transfusion reaction,
steroid for adrenal failure, and intermittent dexamethasone as antiemetic are allowed).
? B12 and folate deficient patients (patients could be rescreened after successful
therapy of B12 and folate deficiency)
? Uncontrolled seizures or uncontrolled hypertension

?Pacientes con SMD con del(5q) aislada
?Pacientes que han recibido tratamiento previo con EPO u otros factores de crecimiento recombinantes independientemente del resultado (se permiten pacientes que hayan recibido tratamiento previo con EPO u otros factores de crecimiento recombinantes durante menos de 4 semanas y no en los 3 meses anteriores a la selección sin una respuesta documentada)
?Se permiten pacientes que reciban tratamiento con corticoesteroides o inmunosupresores para mejorar los parámetros hematológicos (se permite hidrocortisona profiláctica para prevenir la reacción a la transfusión, corticoesteroide para el fallo suprarrenal y dexametasona intermitente como antiemético).
?Pacientes con deficiencia de B12 y folato (los pacientes se podrían re seleccionar después del tratamiento con éxito de la deficiencia de B12 y folato)
?Epilepsia no controlada o hipertensión no controlada

E.5 End points

E.5.1

Primary end point(s)

Difference in proportion of patients achieving an erythroid response within 12 weeks of treatment between the two arms according to modified IWG 2006 criteria (increase in Hb ? 1.5 g/dL)

Diferencia, entre los dos brazos, de la proporción de pacientes que logran una respuesta eritroide a las 12 semanas de tratamiento, según los criterios del IWG 2006 modificados (aumento de Hb ? 1,5 g/dl)

E.5.1.1

Timepoint(s) of evaluation of this end point

baseline at day 1, followed by evaluation at week 2 and after 1,2 and 3 months

en el día 1, seguido por la evaluación en la semana 2 y después de 1,2 y 3 meses

E.5.2

Secondary end point(s)

Proportion of patients achieving a hematological response within 24 weeks of treatment with deferasirox combined with EPO (increase in Hb, improvement of neutropenia and thrombocytopenia) according to modified IWG 2006 criteria.

Proporción de pacientes que logran una respuesta hematológica a las 24 semanas de tratamiento con deferasirox combinado con EPO (aumento de Hb, mejoría de la neutropenia y de la trombocitopenia) según los criterios del IWG 2006 modificados

E.5.2.1

Timepoint(s) of evaluation of this end point

baseline at day 1, followed by evaluation at week 2 and after 1,2, 3, 4, 5 and 6 months

en el día 1, seguido por la evaluación en la semana 2 y después de 1,2,3,4,5 y 6 meses

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

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)

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

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

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

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

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

Argentina

Canada

Colombia

Korea, Republic of

United States

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

Completion of this study as a whole will occur upon the availability and
accuracy verification of the last data point required for statistical
analysis.

La terminación de este estudio en su conjunto tendrá lugar cuando se disponga y se hayan verificado cuidadosamente los últimos datos necesarios para el análisis estadístico

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 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

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

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)

Not different from the expected normal treatment of that condition

No es diferente del tratamiento normal previsto para esa condición

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

2013-10-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-09-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-03-22

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IMP with orphan designation in the indication
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