Clinical Trials Register

Summary
EudraCT Number:	2021-004031-86
Sponsor's Protocol Code Number:	CEST-JIA
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-09-20
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2021-004031-86

A.3

Full title of the trial

“A randomized, two-armed, single-blind, parallel, active controlled, and non-inferiority clinical trial to Compare Efficacy and Safety of
anti TNF-alfa biosimilar molecules to the originators in children with active Juvenile Idiopathic Arthritis”

“Studio clinico randomizzato, a due bracci, in singolo cieco, in parallelo, con controllo attivo e di non inferiorità per comparare efficacia e sicurezza delle molecole anti TNF-alfa biosimilari rispetto agli originators nei bambini con Artrite Idiopatica Giovanile attiva”

A.3.1

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

Efficacy and safety of anti TNF-alfa biosimilar compared to originators in Juvenile Idiopathic Arthritis

Efficacia e sicurezza dei biosimilari anti-TNF-alfa rispetto agli originatori nell’artrite idiopatica giovanile

A.3.2

Name or abbreviated title of the trial where available

CEST-JIA

A.4.1

Sponsor's protocol code number

CEST-JIA

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	FONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AIFA - Italian Medicines Agency
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
B.5.2	Functional name of contact point	UOC Pediatria Media Intensità di Cu
B.5.3	Address:
B.5.3.1	Street Address	Via della Commenda, 9
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20122
B.5.3.4	Country	Italy
B.5.4	Telephone number	0255032458
B.5.5	Fax number	0250320210
B.5.6	E-mail	giovanni.filocamo@policlinico.mi.it

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.2.5	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	Adalimumab biosimilare
D.3.2	Product code	[Adalimumab biosimilare]
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	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.9.2	Current sponsor code	adalimumab biosimilare
D.3.9.3	Other descriptive name	biosimilar adalimumab
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	40
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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: 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.2.5	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	Adalimumab biosimilare
D.3.2	Product code	[Adalimumab biosimilare]
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	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.9.2	Current sponsor code	adalimumab biosimilare
D.3.9.3	Other descriptive name	biosimilar adalimumab
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	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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: 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	40 MG- SOLUZIONE INIETTABILE IN SIRINGHE PRE-RIEMPITE- USO SOTTOCUTANEO- SIRINGA PRERIEMPITA (0,4ML)- 2 SIRINGHE PRE-RIEMPITE + 2 TAMPONI IMBEVUTI DI ALCOOL
D.2.1.1.2	Name of the Marketing Authorisation holder	ABBVIE DEUTSCHLAND GMBH & CO. KG
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Humira
D.3.2	Product code	[Abalimumab bio-originatore]
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	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.9.2	Current sponsor code	adalimumab bio-originatore
D.3.9.3	Other descriptive name	originator adalimumab
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	40
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Etanercept biosimilare
D.3.2	Product code	[Etanercept biosimilare]
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	ETANERCEPT
D.3.9.1	CAS number	185243-69-0
D.3.9.2	Current sponsor code	etanercept biosimilare
D.3.9.3	Other descriptive name	biosimilar Etanercept
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	25
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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: 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.2.5	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	Etanercept biosimilare
D.3.2	Product code	[Etanercept biosimilare]
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	ETANERCEPT
D.3.9.1	CAS number	185243-69-0
D.3.9.2	Current sponsor code	etanercept biosimilare
D.3.9.3	Other descriptive name	biosimilar etanercept
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	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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	ENBREL - 50 MG SOLUZIONE INIETTABILE IN SIRINGA (VETRO DA 1 ML) PRERIEMPITA - USO SOTTOCUTANEO 4 SIRINGHE PRERIEMPITE + 8 TAMPONI IMBEVUTI DI ALCOL
D.2.1.1.2	Name of the Marketing Authorisation holder	PFIZER LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Enbrel
D.3.2	Product code	[Etanercept bio-originatore]
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	ETANERCEPT
D.3.9.1	CAS number	185243-69-0
D.3.9.2	Current sponsor code	etanercept bio-originatore
D.3.9.3	Other descriptive name	etanercept originator
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	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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: 7
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	20 MG- SOLUZIONE INIETTABILE- USO SOTTOCUTANEO- SIRINGA PRE-RIEMPITA (VETRO)- 0,2 ML (20 MG/0,2 ML)- 2 SIRINGHE PRE-RIEMPITE + 2 TAMPONI IMBEVUTI DI ALCOOL
D.2.1.1.2	Name of the Marketing Authorisation holder	ABBVIE DEUTSCHLAND GMBH & CO. KG
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Humira
D.3.2	Product code	[Adalimumab bio-originatore]
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	ADALIMUMAB
D.3.9.1	CAS number	331731-18-1
D.3.9.2	Current sponsor code	adalimumab bio-originatore
D.3.9.3	Other descriptive name	originator adalimumab
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	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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: 8
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	ENBREL - 25 MG SOLUZIONE INIETTABILE IN SIRINGA (VETRO DA 0.5 ML) PRERIEMPITA - USO SOTTOCUTANEO 4 SIRINGHE PRERIEMPITE + 8 TAMPONI IMBEVUTI DI ALCOL
D.2.1.1.2	Name of the Marketing Authorisation holder	PFIZER LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Enbrel
D.3.2	Product code	[Etanercept bio-originatore]
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	ETANERCEPT
D.3.9.1	CAS number	185243-69-0
D.3.9.2	Current sponsor code	etanercept bio-originatore
D.3.9.3	Other descriptive name	etanercept originator
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	25
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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

Juvenile Idiopathic Arthritis

Artrite idiopatica giovanile

E.1.1.1

Medical condition in easily understood language

joint pain and inflammation with juvenile onset

infiammazione articolare ad insorgenza giovanile

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.1
E.1.2	Level	PT
E.1.2	Classification code	10059176
E.1.2	Term	Juvenile idiopathic arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.1
E.1.2	Level	PT
E.1.2	Classification code	10059176
E.1.2	Term	Juvenile idiopathic arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.1
E.1.2	Level	PT
E.1.2	Classification code	10059176
E.1.2	Term	Juvenile idiopathic arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.1
E.1.2	Level	PT
E.1.2	Classification code	10059176
E.1.2	Term	Juvenile idiopathic arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

to evaluate, through a pragmatic trial, safety and efficacy of switching from the adalimumab and etanercept originator molecules versus their biosimilar competitors and vice-versa in children with JIA in clinical remission on anti-TNF medication.

valutare, attraverso uno studio pragmatico, la sicurezza e l'efficacia del passaggio dalle molecole originator di adalimumab ed etanercept ai loro competitor biosimilari e viceversa in bambini con JIA in remissione clinica su farmaci anti-TNF

E.2.2

Secondary objectives of the trial

- to evaluate if the efficacy and safety profile of biosimilars overlaps with that of bio-originators when a switch occurs in patients in clinical remission in current clinical practice
- To evaluate if the efficacy and safety profile of biosimilars overlaps with that of bio-originators in current clinical practice

- valutare se l’efficacia e sicurezza dei farmaci biosimilari si sovrappone a quello dei farmaci bio-originatori quando si verifica uno switch in pazienti in remissione clinica nella pratica clinica attuale
- valutare se l’efficacia e sicurezza dei farmaci biosimilari si sovrappone a quello dei bio-originatori nella pratica clinica attuale

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Children with a diagnosis of JIA according to the ILAR criteria, candidate to treatment with anti-TNF alpha drugs (etanercept or adalimumab) as per clinical indication and per treating physician/family decision
- Moderate to high disease activity despite methotrexate (MTX) treatment for at least 3 months
- Age 2 to 17 years at time of enrolment
- For Etanercept, only patients eligible for receiving authorized biosimilar formulations according to the Summary of Product Characteristics (SmPC), i.e. with the proper weight range, will be enrolled
- Patients should be naive for biologic therapy or should have failed one anti-TNF drug.
- Ability to comply with the entire study procedures, ability to communicate meaningfully with the investigational staff to be applied to the parents and/or patients, as appropriate
- Duly executed, written, informed consent obtained from the patient’s parents.

- bambini con diagnosi di AIG secondo i criteri ILAR e candidate al trattamento con farmaci anti-TNF (etanercept or adalimumab), secondo indicazione clinica e su decisione del medico curante/famiglia
- attività moderata o elevata nonostante il trattamento conmetotressato (MTX) per almeno 3 mesi
- Età compresa tra I 2 e I 17 anni compiuti
- Per etanercept, saranno inclusi I soli pazieneti che potranno ricevere formulazioni di biosimilari approvate in accordo all’RCP, cioè con il peso appropriato
- I pazienti dovranno essere naïve per le terapie biologiche oppure aver fallito un solo trattamento con un farmaco anti-TNF
- capacità di svolgere tutte le procedure di studio, capacità di comunicare efficacemente con lo staff di studio (da applicarsi sia ai genitori che ai pazienti)
- Consenso informato scritto ottenuto dai genitori del paziente.

E.4

Principal exclusion criteria

1. Children with systemic JIA according to ILAR criteria
2. Ongoing treatment in the screening phase with any other second-line agents (except methotrexate) or intravenous immunoglobulin
3. Abnormalities in laboratory values: white blood cell count < 3,000/mm3, a platelet count < 50,000/mm3, levels of serum glutamic oxaloacetic transaminase/asparagine aminotransferase (SGOT/AST) or serum glutamic pyruvic transaminase/alanine aminotransferase (SGPT/ALT) above the upper limit of normal, creatinine levels above the upper limit of normal, chronic proteinuria or hematuria (2–4_/4 on dipstick on 2 consecutive tests)
4. Positive serologic findings of hepatitis B or C
5. Active TB or a history of incompletely treated TB
6. Any live attenuated vaccine within 4 weeks prior to the baseline visit, such as varicella-zoster, oral polio, measle, mumps or rubella vaccines and throughout the study. Killed or inactive vaccine may be permitted based on the investigator’s judgment
7. Prior or current history of malignancy, including lymphoproliferative diseases, other than adequately-treated carcinoma in-situ of the cervix, nonmetastatic squamous cell, or basal cell carcinoma of the skin, within 5 years prior to the baseline visit
8. Prior or current history of other significant concomitant illness(es) that, according to the Investigator’s judgment, would adversely affect the patient’s participation in the study. These include, but are not limited to, cardiovascular, renal, neurological disorder (including demyelinating disease), active infectious diseases, endocrinological, gastrointestinal, hepatobiliary, metabolic, pulmonary (e.g. severe asthma, cystic fibrosis), nonmalignant lymphoproliferative diseases, other lymphatic disease(s), autoimmune disease, psychiatric disorders
9. History of inflammatory bowel disease, severe diverticulitis, or previous gastrointestinal perforation. Uncontrolled diabetes mellitus, defined as glycosylated hemoglobin (HbA1c) =9% at the screening visit
10. A history of COVID-19 infection or vaccination does not exclude participation in the trial if real-time reverse transcription polymerase chain reaction (RT-PCR) confirm the absence of viral RNA in patient specimens
11. For Etanercept, patients with a weight range different from the indications reported in the Summary of Product Characteristics of the biosimilar formulations will not be enrolled. If, during the study, the weight falls outside the indicated ranges for taking biosimilars, the subject will be withdrawn from the study

1. Bambini con AIG sistemica secondo i criteri ILAR
2. Trattamento in corso nella fase di screening con qualsiasi altro agente di seconda linea (eccetto il metotrexato) o immunoglobuline per via endovenosa
3. Anomalie nei valori di laboratorio: conta leucocitaria < 3.000/mm3, conta piastrinica < 50.000/mm3, livelli di transaminasi glutammico ossalacetico/asparagina aminotransferasi (SGOT/AST) o transaminasi glutammico piruvico/alanina aminotransferasi (SGPT/ALT) superiori il limite superiore del normale, livelli di creatinina al di sopra del limite superiore del normale, proteinuria cronica o ematuria (2-4_/4 su strisce reattive su 2 test consecutivi)
4. Reperti sierologici positivi di epatite B o C
5. TBC attiva o anamnesi di TBC trattata in modo incompleto. Pazienti ad alto rischio di contrarre la tubercolosi, come il contatto ravvicinato con individui con tubercolosi attiva o latente
6. Qualsiasi vaccino vivo attenuato nelle 4 settimane precedenti la visita di riferimento, come vaccini contro varicella-zoster, poliomielite orale, morbillo, parotite o rosolia e durante lo studio. Il vaccino ucciso o inattivo può essere consentito in base al giudizio dello sperimentatore
7. Anamnesi pregressa o attuale di tumori maligni, entro 5 anni prima della visita di riferimento
8. Storia precedente o attuale di altre malattie concomitanti significative che, secondo il giudizio dello Sperimentatore, influenzerebbero negativamente la partecipazione del paziente allo studio.
9. Storia di malattia infiammatoria intestinale, diverticolite grave o precedente perforazione gastrointestinale. Diabete mellito non controllato
10. Infezione da COVID-19 in atto documentata dalla positività della Real Time Polimerase Chain Reaction (RT-PCR) per SARS-Cov2
11. Per I pazienti candidati a ricevere etanercept: pazienti con un range di peso differente rispetto a quanto riportato nelle indicazioni d’uso nel “Sommario delle caratteristiche del prodotto” delle formulazioni dei farmaci biosimilari.

E.5 End points

E.5.1

Primary end point(s)

Clinical remission

Remissione clinica

E.5.1.1

Timepoint(s) of evaluation of this end point

18 months

18 mesi

E.5.2

Secondary end point(s)

- Rate of patients who achieve the status of Inactive disease
- Time to inactive disease
- Time spent in inactive disease
- Time to clinical remission
- Cumulative level of disease activity throughout the study period
- Rate of flares
- Rate of uveitis onset/flare
- Frequency of side effects of medications

- tasso di pazienti che raggiunge lo stato di malattia inattiva
- il tempo per ottenere malattia inattiva;
- il tempo trascorso con malattia inattiva;
- il tempo per ottenere la remissione clinica;
- livello cumulativo di attività della malattia durante lo studio
- tasso di riacutizzazioni
- tasso di insorgenza di uveiti e riacutizzazioni
- frequenza degli effetti collaterali dei farmaci

E.5.2.1

Timepoint(s) of evaluation of this end point

6-12-18 months from randomization

6-12-18 mesi dalla randomizzazione

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

160

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

130

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

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

290

F.4.2

For a multinational trial

F.4.2.1

In the EEA

290

F.4.2.2

In the whole clinical trial

290

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After the conclusion of 18-month treatment period of the trial, patients will be followed for a period up to 12 months, depending on and according to timeline imposed by the project (maximal duration 36 months), for the evaluation of disease course, medication requirements, adverse events of medications, and long-term disease-related morbidity

compatibilmente con le tempistiche massime del progetto finanziato (36 mesi), i pazienti, al termine dei 18 mesi di trattamento, saranno seguiti per un periodo di follow-up che durerà al massimo 12 mesi al fine di valutare il decorso della malattia, i trattamenti successivi richiesti e gli eventuali eventi avversi insorti

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Paediatric Rheumatology InterNational Trials Organisation (PRINTO)
G.4.3.4	Network Country	Italy

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-12-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-10-05

P. End of Trial
P.	End of Trial Status	Ongoing

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