Clinical Trials Register

Summary
EudraCT Number:	2010-024381-21
Sponsor's Protocol Code Number:	CRAD001A2314
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:	2013-07-12
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

2010-024381-21

A.3

Full title of the trial

A 12-month, multicenter, open label, randomized, controlled study to evaluate the efficacy, tolerability and safety of early introduction of everolimus, reduced CNI, and early steroid elimination compared to standard CNI, mycophenolate mofetil and steroid regimen in paediatric renal transplant recipients with a 24-month additional safety follow-up

Estudio multicéntrico, abierto, aleatorizado, controlado, de 12 meses de seguimiento para evaluar la eficacia, tolerabilidad y seguridad de la introducción temprana de everolimus, con ICN reducido, y eliminación temprana de esteroides en comparación con un régimen estándar de ICN, micofenolato mofetilo y esteroides en receptores pediátricos de trasplante renal con un seguimiento de seguridad adicional de 24 meses.

A.3.1

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

Pediatric patients that received a transplanted kidney will receive immunosuppressive medication-the calcineurin inhibitor (tacrolimus) and antiproliferative agent (MMF)-until they will be randomized between week 4 and 6 to receive either the same treatment or to switch to the investigational drug everolimus. The patients will be followed up until 3 years after transplantation to evaluate the efficacy, tolerability and safety of the treatments and to assess their impact on renal function.

Pacientes pediátricos que han recibido un trasplante de riñón recibirán medicación inmunosupresora (inhibidor de la cancineurina y agente antiproliferativo) hasta que sean randomizados entre la semana 4 y 6 para recibir el mismo tratamiento o un cambio al fármaco en investigación (everolimus). Los pacientes tendrán un seguimiento de 3 años después del trasplante para evaluar la eficacia, tolerabilidad y seguridad de los tratamientos y para evaluar el impacto en la función renal.

A.3.2

Name or abbreviated title of the trial where available

not applicable

no aplica

A.4.1

Sponsor's protocol code number

CRAD001A2314

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/105/2011

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 (ICRO)
B.5.3	Address:
B.5.3.1	Street Address	Gran Via 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	0034 900 353 036
B.5.5	Fax number	0034 93 247 99 03
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	Certican
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Farmacéutica S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Certican 0,25 mg
D.3.2	Product code	RAD001
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	everolimus
D.3.9.1	CAS number	159351-69-6
D.3.9.2	Current sponsor code	RAD001
D.3.9.3	Other descriptive name	EVEROLIMUS
D.3.9.4	EV Substance Code	SUB02065MIG
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	0.25
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	Certican
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Farmacéutica S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Certican 0,5 mg
D.3.2	Product code	RAD001
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	everolimus
D.3.9.1	CAS number	159351-69-6
D.3.9.2	Current sponsor code	RAD001
D.3.9.3	Other descriptive name	EVEROLIMUS
D.3.9.4	EV Substance Code	SUB02065MIG
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	0.5
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.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	Certican
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Farmacéutica S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Certican 0,75 mg
D.3.2	Product code	RAD001
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	everolimus
D.3.9.1	CAS number	159351-69-6
D.3.9.2	Current sponsor code	RAD001
D.3.9.3	Other descriptive name	EVEROLIMUS
D.3.9.4	EV Substance Code	SUB02065MIG
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	0.75
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: 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	Certican
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Farmacéutica S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Certican 1 mg
D.3.2	Product code	RAD001
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	everolimus
D.3.9.1	CAS number	159351-69-6
D.3.9.2	Current sponsor code	RAD001
D.3.9.3	Other descriptive name	EVEROLIMUS
D.3.9.4	EV Substance Code	SUB02065MIG
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	1
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: 5
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	Certican
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Farmacéutica S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Certican 0,1 mg
D.3.2	Product code	RAD001
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	everolimus
D.3.9.1	CAS number	159351-69-6
D.3.9.2	Current sponsor code	RAD001
D.3.9.3	Other descriptive name	EVEROLIMUS
D.3.9.4	EV Substance Code	SUB02065MIG
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	0.1
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: 6
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	Certican
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Farmacéutica S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Certican 0,25 mg
D.3.2	Product code	RAD001
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	everolimus
D.3.9.1	CAS number	159351-69-6
D.3.9.2	Current sponsor code	RAD001
D.3.9.3	Other descriptive name	EVEROLIMUS
D.3.9.4	EV Substance Code	SUB02065MIG
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	0.25
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: 7
D.1.2 and D.1.3	IMP Role	Comparator
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	Prograf
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Prograf 0,5 mg
D.3.2	Product code	FK-506
D.3.4	Pharmaceutical form	Capsule, hard
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	TACROLIMUS
D.3.9.1	CAS number	104987-11-3
D.3.9.3	Other descriptive name	FK-506
D.3.9.4	EV Substance Code	SUB10797MIG
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	0.5
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.IMP: 8
D.1.2 and D.1.3	IMP Role	Comparator
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	Prograf
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Prograf 1 mg
D.3.2	Product code	FK-506
D.3.4	Pharmaceutical form	Capsule, hard
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	TACROLIMUS
D.3.9.1	CAS number	104987-11-3
D.3.9.3	Other descriptive name	FK-506
D.3.9.4	EV Substance Code	SUB10797MIG
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	1
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: 9
D.1.2 and D.1.3	IMP Role	Comparator
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	Prograf
D.2.1.1.2	Name of the Marketing Authorisation holder	Astellas Pharma S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Prograf 5 mg
D.3.2	Product code	FK-506
D.3.4	Pharmaceutical form	Capsule, hard
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	TACROLIMUS
D.3.9.1	CAS number	104987-11-3
D.3.9.3	Other descriptive name	FK-506
D.3.9.4	EV Substance Code	SUB10797MIG
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.IMP: 10
D.1.2 and D.1.3	IMP Role	Comparator
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	Cellcept
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Farma S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Cellcept 250 mg
D.3.4	Pharmaceutical form	Capsule
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	Mycophenolate mofetil
D.3.9.1	CAS number	115007-34-6
D.3.9.4	EV Substance Code	SUB03360MIG
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	250
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: 11
D.1.2 and D.1.3	IMP Role	Comparator
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	Cellcept
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Farma S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Cellcept 500 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	Mycophenolate mofetil
D.3.9.1	CAS number	115007-34-6
D.3.9.4	EV Substance Code	SUB03360MIG
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: 12
D.1.2 and D.1.3	IMP Role	Comparator
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	Cellcept
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Farma S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Cellcept 200 mg/ml
D.3.4	Pharmaceutical form	Oral suspension
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	Mycophenolate mofetil
D.3.9.1	CAS number	115007-34-6
D.3.9.4	EV Substance Code	SUB03360MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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	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: 13
D.1.2 and D.1.3	IMP Role	Comparator
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	Myfortic
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Farmaceutica S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Myfortic 180mg
D.3.4	Pharmaceutical form	Gastro-resistant 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	MYCOPHENOLATE SODIUM
D.3.9.1	CAS number	37415-62-6
D.3.9.2	Current sponsor code	Myfortic
D.3.9.3	Other descriptive name	MYCOPHENOLATE SODIUM
D.3.9.4	EV Substance Code	SUB16447MIG
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	180
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: 14
D.1.2 and D.1.3	IMP Role	Comparator
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	Myfortic
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Farmaceutica S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Myfortic 360mg
D.3.4	Pharmaceutical form	Gastro-resistant 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	MYCOPHENOLATE SODIUM
D.3.9.1	CAS number	37415-62-6
D.3.9.2	Current sponsor code	Myfortic
D.3.9.3	Other descriptive name	MYCOPHENOLATE SODIUM
D.3.9.4	EV Substance Code	SUB16447MIG
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	360
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

Prevention of acute rejection in paediatric recipients of a renal transplant

Prevención del rechazo agudo en receptores pediátricos de un trasplante renal.

E.1.1.1

Medical condition in easily understood language

Pediatric patients that will undergo kidney transplantation

Pacientes pediátricos que reciban un trasplante renal.

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	SOC
E.1.2	Classification code	10038359
E.1.2	Term	Renal and urinary disorders
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

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 estimate the rate of the composite efficacy endpoint of BPAR, graft loss or death at 12 months post transplantation in primary paediatric kidney transplant recipients converted at 4-6 weeks post-transplantation from MMF + standard TAC regimen and steroids, to everolimus + reduced dose TAC regimen and steroid withdrawal at 6 months, versus continuation of MMF + standard TAC regimen and steroids.
- To evaluate renal function assessed by Glomerular Filtration Rate (eGFR) estimated by the Schwartz formula (abbreviated) at month 12.

- Calcular la tasa de la variable compuesta de eficacia de rechazo agudo comprobado por biopsia (RACB), pérdida del injerto o muerte a los 12 meses posteriores al trasplante renal en receptores pediátricos de un primer trasplante renal a quienes a las 4-6 semanas posteriores al trasplante se les haya cambiado el MMF + régimen estándar de TAC y esteroides por el régimen con everolimus + dosis reducida de TAC y retirada de esteroides a los 6 meses, en comparación con MMF + régimen estándar de TAC y esteroides.
- Evaluar la función renal evaluada mediante la tasa de filtrado glomerular (TFGe) estimada mediante la fórmula de Schwartz (abreviada) (Schwartz, 2009) en el mes 12.

E.2.2

Secondary objectives of the trial

- To evaluate each of the components of the composite efficacy endpoint
- To evaluate the time to event and severity of BPAR
- To evaluate incidence of biopsy proven antibody mediated rejection
- To Evaluate the incidence/progression of chronic allograft nephropathy (Interstitial Fibrosis and Tubular Atrophy IF/TA) by histopathology.
- To evaluate growth and development, including linear growth, sexual maturation, hormonal gonadal axis (estradiol, testosterone, LH, FSH, inhibin B), TSH, T3 and T4

- Evaluar cada uno de los componentes de la variable compuesta de eficacia.
- Evaluar el tiempo hasta el acontecimiento y la severidad del RACB.
- Evaluar la incidencia de rechazo mediado por anticuerpo comprobado por biopsia
- Evaluar la evolución de la función del aloinjerto renal con el tiempo.
- Evaluar la incidencia/progresión de nefropatía crónica del aloinjerto (Fibrosis Intersticial y Atrofia Tubular FI/AT) mediante histopatología.
- Evaluar el crecimiento y desarrollo, incluido el crecimiento lineal, la madurez sexual, el eje gonadal hormonal (estradiol, testosterona, LH, FSH, inhibina B), TSH, T3 y T4.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria at baseline (transplantation)
1-Written informed consent/assent must be obtained from the parent(s) or legal guardian before any assessment is performed.
2- Primary paediatric kidney transplant greater than or equal to 1 year and younger than 18 years receiving a primary deceased donor or non-HLA identical living donor (related or unrelated) renal transplant.

Inclusion criteria at randomization (4-6 weeks after transplantation)
1-Patients on TAC + MMF + steroids.
2- Renal function with eGFR > 50 ml/min/1.73 m2 (Schwartz formula-abbreviated).

Criterios de inclusión en la visita basal (trasplante)
1. Deberá obtenerse del (de los) padre(s) o tutor legal el consentimiento/asentimiento informado por escrito antes de realizar ninguna evaluación.
2. Receptor pediátrico de un primer o segundo trasplante renal mayor o de edad equivalente a 1 año o menor de 18 años que reciba un trasplante renal de donante cadáver o donante vivo no HLA idéntico (relacionado o no relacionado).
Criterios de inclusión en la aleatorización (4-6 semanas después del trasplante)
1. Pacientes en tratamiento con TAC + MMF + esteroides.
2. Función renal con TFGe > 40 ml/min/1,73 m2 (fórmula de Schwartz - abreviada).

E.4

Principal exclusion criteria

exclusion criteria at baseline:
1- Recipients of kidneys from donors with known renal disease (such as diabetes nephropathy, nephrosclerosis), at the time of transplant.
2 - Recipients of a kidney with a cold ischemia time > 24 hours.
3 - Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
4 - History of hypersensitivity or contraindications to any of the study drugs or to drugs of similar chemical classes, or to any of the excipients.
5 - History of malignancy of any organ system treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.

other protocol-defined exclusion criteria may apply

Exclusion criteria at Randomization (4-6 weeks after transplantation)
1 - Patients with ongoing or currently treated episodes of acute rejection (any grade) or a steroid resistant acute rejection at the time of randomization.
2 - Patients who experienced acute cellular rejection (Banff ?1B) or any antibody mediated acute rejection or patients considered at high risk of antibody mediated acute rejection by the investigator assessment (e.g. presence of newly formed DSA, histological suspicion) at any time before randomization (as the DSA quantitative threshold to define high risk is not fully established, the assessment of the risk will be made after discussion between the laboratory expert and the investigator who will take into account all information available and apply best judgment).
3 - Patients with ongoing wound healing problems, clinically significant wound infection requiring continued therapy or other severe surgical complication in the opinion of the investigator.
4 - Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) and can not discontinue the treatment (see Appendix 6 for list of medications).
5 - Patients with nephrotic range proteinuria (protein to creatinine ratio ?2.0 mg/mg or 200 mg/mmol.

other protocol-defined exclusion criteria may apply

1. Receptores de riñones procedentes de donantes con enfermedad renal conocida (tales como nefropatía diabética, nefroesclerosis), en el momento del trasplante.
2. Receptores de un riñón con un tiempo de isquemia fría > 24 horas.
3. Antecedentes de hipersensibilidad o contraindicaciones a cualquiera de las medicaciones del estudio o a fármacos de clases químicas similares, o a cualquiera de los excipientes.
4. Antecedentes de enfermedad maligna de cualquier sistema orgánico tratada o no tratada, que conlleve el posible riesgo de recurrencia de acuerdo con las guías actuales (Apéndice 10).
5. Mujeres embarazadas o en período de lactancia, donde el embarazo se define como el estado de una mujer después del embarazo y hasta la finalización de la gestación, confirmado mediante un resultado positivo en la prueba de laboratorio hCG (> 9 mIU/mL).
6. Pacientes mujeres en edad fértil, definidas como todas las mujeres fisiológicamente capaces de quedarse embarazadas, EXCEPTO si están de acuerdo en abstenerse de la actividad sexual.
7. Pacientes que sean receptores de multitrasplantes de órganos sólidos o que previamente hayan recibido órganos trasplantados excepto un primer trasplante renal.
8. Receptores de riñones procedentes de donantes vivos HLA idénticos relacionados
9. Receptores de riñones procedentes de donantes mayores de 60 años de edad.
10. Receptor de aloinjerto ABO incompatible o una prueba cruzada positiva para linfocitos T.
11. Anticuerpos reactivos anti-HLA Clase I/II más recientes > 20% mediante análisis basado en citotoxicidad dependiente del complemento (CDC) o > 50% mediante citometría de flujo o enzimoinmunoanálisis de adsorción (ELISA).
12. Pacientes que se considere que presentan un alto riesgo de rechazo agudo mediado por anticuerpos (p. ej., presencia de ADE preformados) (debido a que el umbral cuantitativo de ADE para definir el alto riesgo no está completamente establecido, la evaluación del riesgo se realizará después de que el experto del laboratorio y el investigador lo hayan comentado, quienes tendrán en cuenta toda la información disponible y aplicarán el mejor juicio).
13. Pacientes con resultado positivo para el virus de la inmunodeficiencia humana VIH) o Hepatitis C (PCR sólo) o positivo para el antígeno de superficie de la hepatitis B. Los resultados de serología vírica que se obtengan dentro de los 6 meses anteriores a la aleatorización son aceptables.
14. Los pacientes que hayan recibido un aloinjerto de un donante positivo para el virus de la inmunodeficiencia humana (VIH), positivo para el antígeno de superficie de la Hepatitis B (HBsAg) o para el virus de la Hepatitis C (VHC).
15. Pacientes con hepatopatía severa (pruebas anormales de la función hepática, es decir, AST, ALT o bilirrubina total >3 veces LSN).
16. Pacientes con trastornos pulmonares restrictivos u obstructivos severos.
17. Pacientes con antecedentes de síndrome urémico hemolítico no asociado con diarrea (HUS).
18. Paciente con alergia grave que requiera tratamiento agudo (dentro de las 4 semanas del trasplante) o crónico que evitaría la posible exposición del paciente a everolimus, o con hipersensibilidad a fármacos similares a everolimus (p. ej., eritromicina u otros antibióticos macrólidos) o a cualquier componente de la formulación o a fármacos de clases químicas similares.
19. Pacientes con glomerulosclerosis segmentaria y focal no genética.
20. Pacientes que requieran terapia con hormona del crecimiento durante el primer año después del trasplante.
21. Pacientes que tengan una infección sistémica severa actual a juicio investigador, que requiera terapia continuada que interferiría con los objetivos del estudio.
Criterios de exclusión en la Aleatorización (4-6 semanas después del trasplante)
1. Uso de otros fármacos en investigación en el momento de la aleatorización, o en los 30 días o 5 semividas antes de la aleatorización, lo que sea más largo.
2. Pacientes con episodios tratados en curso o recientes (en las 2 semanas previas a la aleatorización) de rechazo agudo (de cualquier grado) o un rechazo agudo corticorresistente en cualquier momento de la aleatorización.
3. Pacientes que hayan presentado rechazo celular agudo (Banff ?1B) o cualquier rechazo agudo mediado por anticuerpos o pacientes que se considere que tienen un alto riesgo de rechazo agudo mediado por anticuerpos, según la evaluación del investigador (p. ej., presencia de AED de reciente formación, sospecha histológica) en cualquier momento antes de la aleatorización (debido a que el umbral cuantitativo de los ADE para definir el alto riesgo no está completamente establecido, la evaluación del riesgo se realizará después de que el experto del laboratorio y el investigador lo hayan comentado, quienes tendrán en cuenta toda la información disponible y aplicarán el mejor juicio).

Ver protocolo página 30 versión en castellano.

E.5 End points

E.5.1

Primary end point(s)

1- The incidence of composite efficacy failure including BPAR, death, and graft loss at 12 months. Local biopsy readings will be used to determine the occurrence of BPAR.
2- Renal function will be assessed by eGFR estimated by the Schwartz formula (abbreviated) at month 12.

? Calcular la tasa de la variable compuesta de eficacia de RACB, pérdida del injerto o muerte a los 12 meses posteriores al trasplante en receptores pediátricos de un primer trasplante renal a quienes a las 4-6 semanas posteriores al trasplante se les haya cambiado el MMF + régimen estándar de TAC y esteroides por el régimen con everolimus + dosis reducida de TAC y retirada de esteroides a los 6 meses, en comparación con MMF + régimen estándar de TAC y esteroides.
? Evaluar la función renal evaluada mediante la tasa de filtrado glomerular (TFGe) estimada mediante la fórmula de Schwartz (abreviada) (Schwartz, 2009) en el mes 12.

E.5.1.1

Timepoint(s) of evaluation of this end point

Month 12 after transplantation.

Mes 12 después del trasplante

E.5.2

Secondary end point(s)

1- Components of the composite efficacy endpoint;
2- Incidences of biopsy proven antibody mediated rejection
3- Incidence/progression of chronic allograft nephropathy (interstitial fibrosis and tubular atrophy, IF/TA);
4- Safety (evolution of renal function over time, incidence of proteinuria, the frequency of drug-related side effects (CNI-related, mTOR-inhibitor-specific or MMF-class effects), assessment of growth and development, the frequency of AEs/Infections, SAEs.

- Evaluar cada uno de los componentes de la variable compuesta de eficacia.
- Evaluar el tiempo hasta el acontecimiento y la severidad del RACB (Banff 2009).
- Evaluar la incidencia de rechazo mediado por anticuerpo comprobado por biopsia
- Evaluar la evolución de la función del aloinjerto renal con el tiempo.
- Evaluar la incidencia/progresión de nefropatía crónica del aloinjerto (Fibrosis Intersticial y Atrofia Tubular FI/AT) mediante histopatología.
- Evaluar el crecimiento y desarrollo, incluido el crecimiento lineal, la madurez sexual, el eje gonadal hormonal (estradiol, testosterona, LH, FSH, inhibina B), TSH, T3 y T4.

E.5.2.1

Timepoint(s) of evaluation of this end point

Month 12 and 36 after transplantation.

Mes 12 y 36 después del trasplante

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)

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

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

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

Belgium

Brazil

Canada

France

Germany

Guatemala

Hungary

Italy

Norway

Poland

Spain

Sweden

Turkey

United Kingdom

United States

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

Yes

F.1.1

Number of subjects for this age range:

106

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

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)

F.1.3

Elderly (>=65 years)

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

106

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)

All patients discontinuing the study medication prior to the 36 months treatment period have to be contacted at scheduled months 6, 12, 24 and 36 visits to obtain follow-up information according to study protocol.
After study completion, treatment of a patient should be according to discretion of the investigator.

Todos los pacientes que discontinúen la medicación del ensayo antes del periodo de tratamiento de 36 meses tienen que ser contactados en las visitas programadas de los meses 6, 12, 24 y 36 para obtener información de seguimiento acorde al protocolo del ensayo. Después de la finalización del ensayo, el tratamiento del paciente será según decisión del investigador.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-09-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-07-29

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-09-24

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Orphan Designation Number:
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