Clinical Trials Register

Summary
EudraCT Number:	2012-005180-27
Sponsor's Protocol Code Number:	1517-CL-0608
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:	2013-04-09
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

2012-005180-27

A.3

Full title of the trial

A Phase 3, Randomized, Double-Blind, Placebo Controlled Study of the Efficacy and Safety of FG-4592 for the Treatment of Anemia in Chronic Kidney Disease Patients not on Dialysis

Estudio de fase 3, aleatorizado, doble ciego y controlado con placebo de la eficacia y la seguridad de FG-4592 en el tratamiento de la anemia en pacientes con insuficiencia renal crónica no tratados con diálisis

A.3.1

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

FG-4592 in the Treatment of Anemia in Chronic Kidney Disease Patients

FG-4592 en el tratamiento de la anemia en pacientes con Insuficiencia Renal Crónica

A.4.1

Sponsor's protocol code number

1517-CL-0608

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	Astellas Pharma Europe B.V.
B.1.3.4	Country	Netherlands
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	Astellas Pharma Europe B.V.
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Astellas Pharma Europe B.V.
B.5.2	Functional name of contact point	Service Desk - Global Clinical Dev.
B.5.3	Address:
B.5.3.1	Street Address	Sylviusweg 62
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 BE
B.5.3.4	Country	Netherlands
B.5.6	E-mail	contact@nl.astellas.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.3.2	Product code	FG-4592 - 20 mg
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	ASP1517
D.3.9.1	CAS number	808118-40-3
D.3.9.2	Current sponsor code	FG-4592
D.3.9.3	Other descriptive name	ASP1517
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	20
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	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.3.2	Product code	FG-4592 - 50 mg
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	ASP1517
D.3.9.1	CAS number	808118-40-3
D.3.9.2	Current sponsor code	FG-4592
D.3.9.3	Other descriptive name	ASP1517
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	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	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.3.2	Product code	FG-4592 - 100 mg
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	ASP1517
D.3.9.1	CAS number	808118-40-3
D.3.9.2	Current sponsor code	FG-4592
D.3.9.3	Other descriptive name	ASP1517
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	100
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
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

Anemia in CKD patients not on dialysis

Anemia en pacientes con insuficiencia renal crónica que no reciban diálisis.

E.1.1.1

Medical condition in easily understood language

Anemia in patients with chronic kidney disease

Anemia en pacientes con Insuficiencia renal crónica.

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10002272
E.1.2	Term	Anemia
E.1.2	System Organ Class	100000004851

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the efficacy of FG-4592 in the treatment of anemia in non-dialysis Chronic Kidney Disease (CKD) subjects.

Evaluar la eficacia de FG-4592 en el tratamiento de la anemia en sujetos con insuficiencia renal crónica (IRC) no tratados con diálisis.

E.2.2

Secondary objectives of the trial

- To evaluate the safety of FG-4592.
- To evaluate health-related quality of life benefit.
- To evaluate the need for rescue therapy. (RBC transfusion, ESA, or IV Iron)

* Evaluar la seguridad de FG-4592
* Evaluar la mejoría de la calidad de vida relacionada con la salud
* Evaluar la necesidad de tratamiento de rescate: transfusión de eritrocitos (RBC), agentes estimulantes de la eritropoyesis (ESA) o hierro intravenoso (i.v.).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subject is eligible for the study if all of the following apply:
- Age >= 18 years
- Diagnosis of chronic kidney disease, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4 or 5, not receiving dialysis; with an eGFR <60 mL/min/1.73 m2 estimated using the abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) equation.
- Mean of the three most recent Hb values during the Screening period, obtained at least 4 days apart, must be <=10.0 g/dL, with a difference of <=1.0 g/dL between the highest and the lowest values.
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) <=3 x upper limit of normal (ULN), and total bilirubin (TBL) <=1.5 x ULN.
- Body weight of 45.0 kg up to a maximum of 160.0 kg.

Un sujeto podrá participar en el estudio si se cumple todo lo siguiente:
-El sujeto tiene >= 18 años de edad
-El sujeto está diagnosticado de insuficiencia renal crónica, en estadio 3, 4 o 5 del estudio Kidney Disease Outcomes Quality Initiative (KDOQI), y no recibe diálisis; tiene un FGe <60 (ml/min)/1,73 m2 estimado utilizando la ecuación abreviada de 4 variables del estudio Modification of Diet in Renal Disease (MDRD).
-La media de los tres valores de Hb más recientes durante el período de selección, separados entre sí al menos 4 días, debe ser <=10,0 g/dl, con una diferencia <=1,0 g/dl entre el mayor y el menor valor.
-Las concentraciones de alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST) del sujeto son <=3 x límite superior de la normalidad (LSN), y la bilirrubina total (BTL) es <=1,5 x LSN.
-El peso corporal del sujeto es desde 45,0 kg hasta un máximo de 160,0 kg.

E.4

Principal exclusion criteria

Subject will be excluded from participation if any of the following apply:
- Any ESA treatment within 12 weeks prior to randomization.
- More than one dose of IV iron within 12 weeks prior to randomization.
- RBC transfusion within 8 weeks prior to randomization.
- Chronic inflammatory disease that could impact erythropoiesis.
- Myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (e.g., pulmonary embolism) within 12 weeks prior to randomization.
- Two or more blood pressure values of systolic BP>=150 mmHg or
diastolic BP>=95mmHg within 2 weeks prior to randomization.

Se excluirá al sujeto de este estudio si se cumple cualquiera de los siguientes:
-Cualquier tratamiento con ESA en las 12 semanas previas a la aleatorización.
-Más de una dosis de hierro i.v. en las 12 semanas previas a la aleatorización.
-Transfusión de RBC en las 8 semanas previas a la aleatorización.
-Enfermedad inflamatoria crónica que podría influir en la eritropoyesis.
-Infarto de miocardio, un síndrome coronario agudo, un accidente cerebrovascular, una crisis convulsiva o un episodio trombótico/tromboembólico (p. ej., embolia pulmonar) en las 12 semanas previas a la aleatorización.
-Dos o más valores de PA sistólica >=150 mmHg o PA diastólica >=95mmHg en las 2 semanas previas a la aleatorización.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variable is Hb response.

La variable de eficacia principal es la respuesta de la Hb.

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to and including week 24

Hasta la semana 24 (inclusive)

E.5.2

Secondary end point(s)

- Hb change from baseline to the average of weeks 28-36
- LDL Change from baseline to the average of weeks 12-28
- Physical Functioning subscore and Vitality subscore change from baseline to the average of week 12-28.
- BP effect
- Occurence of hypertension
- Having received rescue therapy (composite of RBC transfusions, ESA use and IV iron)

-Cambio de la Hb desde BL hasta la Hb media de las semanas 28-36
-Cambio del LDL desde BL hasta la media de las semanas 12-28
-Cambio de la subpuntuación de actividad física (AF) de la escala SF-36 desde BL hasta el promedio de las semanas 12-28
-Efecto sobre la Presión Arterial.
-Aparición de Hipertensión.
-Haber recibido terapia de rescate (criterio de valoración compuesto de transfusiones de RBC, uso de ESA y hierro i.v.).

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 12 to week 28

De la semana 12 a la 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

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

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

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

Bulgaria

France

Hungary

Italy

Poland

Romania

Russian Federation

Serbia

Spain

Turkey

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

Última visita del último paciente

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:

420

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

180

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

540

F.4.2.2

In the whole clinical trial

600

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)

None

Ninguno

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

2013-06-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-05-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-11-01

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