Clinical Trials Register

Summary
EudraCT Number:	2012-002324-32
Sponsor's Protocol Code Number:	I4V-MC-JADZ
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-01-11
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-002324-32

A.3

Full title of the trial

A Randomized, Double-Blind, Active-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib (LY3009104) in Patients with Moderately to Severely Active Rheumatoid Arthritis Who Have Had Limited or No Treatment with Disease-Modifying Antirheumatic Drugs

Studio di fase III randomizzato, in doppio cieco con controllo attivo, per valutare l'efficacia e la sicurezza di Baricitinib (LY3009104) in pazienti con artrite reumatoide attiva da moderata a grave con previa esposizione limitata o nulla a farmaci antireumatici modificanti la malattia

A.3.1

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

A phase 3 study in moderate to severe rheumatoid arthritis

Studio di fase 3 sull'artrite reumatoide moderata e severa

A.3.2

Name or abbreviated title of the trial where available

RA - BEGIN

A.4.1

Sponsor's protocol code number

I4V-MC-JADZ

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	ELI LILLY AND COMPANY
B.1.3.4	Country	United States
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	Eli Lilly and Company
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Eli Lilly and Company
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Lilly Corporate Center
B.5.3.2	Town/ city	Indianapolis
B.5.3.3	Post code	IN46285
B.5.3.4	Country	Italy
B.5.4	Telephone number	0044 1276 483015
B.5.5	Fax number	0044 1276 483378
B.5.6	E-mail	EU_Lilly_Clinical_Trials@lilly.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.3.1	Product name	BARICITINIB
D.3.2	Product code	LY3009104
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.3.9.2	Current sponsor code	LY3009104
D.3.9.3	Other descriptive name	Baricitinib
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	4
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	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	Maxtrex
D.2.1.1.2	Name of the Marketing Authorisation holder	Pharmacia Limited
D.2.1.2	Country which granted the Marketing Authorisation	United States
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.3.4	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	METHOTREXATE
D.3.9.1	CAS number	59-05-2
D.3.9.4	EV Substance Code	SUB08856MIG
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	2.5
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	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.3.1	Product name	BARICITINIB
D.3.2	Product code	LY3009104
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.3.9.2	Current sponsor code	LY3009104
D.3.9.3	Other descriptive name	Baricitinib
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	2
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	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	Maxtrex
D.2.1.1.2	Name of the Marketing Authorisation holder	Pharmacia Limited
D.2.1.2	Country which granted the Marketing Authorisation	United States
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.3.4	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	METHOTREXATE
D.3.9.1	CAS number	59-05-2
D.3.9.4	EV Substance Code	SUB08856MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
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	Capsule
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

Moderately to severely active rheumatoid arthritis

Artrite reumatoide attiva da moderata a grave

E.1.1.1

Medical condition in easily understood language

Rheumatoid arthritis

Artrite reumatoide

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	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10028395
E.1.2	Term	Musculoskeletal and connective tissue disorders
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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue 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

Determine whether baricitinib monotherapy is noninferior to MTX monotherapy in the treatment of patients with moderate to severe active RA who have had limited or no treatment with MTX and are naive to other conventional or biologic DMARDs, as assessed by the proportion of patients achieving a 20% improvement in American College of Rheumatology criteria (ACR20) at Week 24.

Stabilire se la monoterapia con baricitinib sia non inferiore rispetto alla monoterapia con MTX nel trattamento di pazienti affetti da AR attiva da moderata a grave, con esposizione limitata o assente alla terapia con MTX e naïve nei riguardi di altri DMARD tradizionali o biologici, come valutato mediante la percentuale di pazienti che consegue un miglioramento del 20% nei criteri dell'American College of Rheumatology (ACR20) alla Settimana 24.

E.2.2

Secondary objectives of the trial

• proportion of patients achieving ACR20 at Week 24 for baricitinib plus MTX versus MTX monotherapy • change from baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) score • change from baseline to Week 24 in DAS28–high-sensitivity C reactive protein (hsCRP) • change from baseline to Week 24 in structural joint damage as measured by modified Total Sharp Score (mTSS [van der Heijde method]) for baricitinib plus MTX versus MTX monotherapy • area under the curve (AUC) up to Week 24 in HAQ-DI score for baricitinib monotherapy versus MTX monotherapy • AUC up to Week 24 in DAS28-hsCRP score for baricitinib monotherapy versus MTX monotherapy

•percentuale pazienti che soddisfa i criteri ACR20 alla settimana 24•cambiamento,dal basale alla settimana 24,del punteggio dell'Health Assessment Questionnaire- Disability Index (HAQ-DI)•cambiamento,dal basale alla Settimana 24,del punteggio del DAS28–highsensitivity hsCRP•cambiamento,dal basale alla settimana 24,del danno strutturale alle articolazioni, misurato con il punteggio mTSS• AUC fino alla settimana 24 nel punteggio HAQ-DI •AUC fino alla settimana 24 nel punteggio DAS28-hsCR

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

OTHER SUBSTUDIES:
Protocol Addendum I4V-MC-JADZ(1) Approved: 14-Aug-2012 To evaluate the efficacy of Baricitinib in patients with RA as measured by MRI of the dominant hand and wrist.

ALTRI SOTTOSTUDI:
Protocol Addendum I4V-MC-JADZ(1) Approvato: 14-Ago-2012 Valutazione di efficacia di Baricitinib mediante risonanza magnetica alla mano dominante e al polso.

E.3

Principal inclusion criteria

• are at least 18 years of age • have a diagnosis of adult-onset RA as defined by ACR/EULAR 2010 Criteria for the Classification of RA • have documented history of positive rheumatoid factor and/or cyclic citrullinated peptide (CCP) antibody test • have moderately to severely active RA defined as the presence of at least 6/68 tender joints and at least 6/66 swollen joints • have a C-reactive protein (or hsCRP) measurement ≥1.2 times the upper limit of normal (ULN) • have had limited or no treatment with MTX

Sono eleggibili per l'inclusione in questo studio pazienti di ambo i sessi, di età minima di 18 anni, affetti da AR con esordio in età adulta in base ai criteri ACR/EULAR 2010 per la classificazione dell'AR. I pazienti devono avere un'anamnesi documentata di positività del test per fattori reumatoidi e/o anticorpi anti-peptidi citrullinati ciclici, AR attiva definita come la presenza di almeno 6 articolazioni dolenti su 68 e di 6 articolazioni gonfie su 66, e con una misurazione hsCRP _1,2 volte il limite superiore della norma (ULN). Inoltre, i pazienti devono avere avuto un trattamento limitato o nullo con MTX ed essere naïve nei riguardi di altri DMARD tradizionali o biologici

E.4

Principal exclusion criteria

• have received conventional DMARDs other than MTX•are currently receiving corticosteroids at doses >10 mg per day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids•have started treatment with NSAIDs or have been receiving an unstable dosing regimen of NSAIDs•have started a new physiotherapy treatment for RA in the 2 weeks prior to study entry•have ever received any biologic DMARD•have received interferon therapy within 4 weeks prior to study entry•have received any parenteral corticosteroid administered by intramuscular or intravenous inj•have had 3 or more joints injected with intraarticular corticosteroids•have active fibromyalgia that would make it difficult to appropriately assess RA activity•have a diagnosis of any systemic inflammatory condition other than RA•have a diagnosis of Felty’s syndrome•have had any major surgery within 8 weeks of study entry•have experienced any of the following within 12 weeks of study entry:myocardial infarction,unstable ischemic heart disease,stroke, or NYHA Stage IV heart failure•have a history or presence of cardiovascular,respiratory,hepatic, gastrointestinal,endocrine,hematological,neurological,or neuropsychiatric disorders or any other serious and/or unstable illness•are largely or wholly incapacitated permitting little or no self care, such as, being bedridden or confined to a wheelchair•have an eGFR based on the most recent available serum creatinine using the Modification of Diet in Renal Disease method of <40 mL/min/1.73 m2•have a history of chronic liver disease with the most recent available AST or ALT>1.5 times the ULN or the most recent available total bilirubin ≥1.5 times the ULN•have lymphoproliferative disease;or signs or symptoms suggestive of possible lymphoproliferative disease,including lymphadenopathy or splenomegaly;or active primary or recurrent malignant disease;or have been in remission from clinically significant malignancy for <5 years•have been exposed to a live vaccine within 12 w prior to planned randomization or are expected to need/receive a live vaccine during the course of the study•have a current or recent clinically serious viral,bacterial,fungal,or parasitic infection•have had symptomatic herpes zoster infection within 12 w prior to study entry•have a history of disseminated/complicated herpes zoster•are immunocompromised •have a history of active hepatitis B virus,hepatitis C virus,or human immunodeficiency virus•have screening laboratory test values outside the reference range for the population or investigative site•have screening ECG abnormalities that are clinically significant•have symptomatic herpes simplex at the time of study enrollment•have evidence of active or latent TB as documented by a positive purified protein

• paz che hanno ricevuto DMARD convenzionali diversi MTX•paz in trattamento con corticosteroidi a dosi> 10 mg al giorno di prednisone (o equivalente) o hanno ricevuto un dosaggio non stabile di corticosteroidi• paz che hanno iniziato il trattamento con FANS o hanno ricevuto un dosaggio instabile di FANS•paz che hanno iniziato fisioterapia come nuovo trattamento per l'artrite reumatoide nelle 2 settimane prima dell'ingresso nello studio•paz che hanno ricevuto qualunque DMARD biologico•paz che hanno ricevuto terapia con interferone entro 4 sett prima dell'ingresso nello studio•paz che hanno ricevuto qualsiasi corticosteroide parenterale somministrato per via intramuscolare o endovenosa•paz che hanno avuto 3 o più articolazioni trattate con corticosteroidi intra-articolari•paz con fibromialgia attiva che renderebbe difficile valutare adeguatamente l'attività RA•paz con diagnosi di una condizione infiammatoria sistemica diverso RA•paz con diagnosi di sindrome di Felty•paz che hanno avuto qualsiasi intervento chirurgico importante entro 8 sett dall’ingresso nello studio•paz con una delle seguenti condizioni manifestate entro 12 sett dall’ingresso nello studio:infarto del miocardio,cardiopatia ischemica instabile,ictus o insufficienza cardiaca NYHA stadio IV •paz con storia o presenza di malattie cardiovascolari,respiratorie,epatiche,gastrointestinali,endocrine,ematologiche,disturbi neurologici o neuropsichiatrici•paz sono in gran parte o totalmente inabili a prendersi poca o nessuna cura di sé, ad esempio, costretti a letto o sulla sedia a rotelle•paz con eGFR <40 mL/min/1.73 m2•paz con storia di malattia epatica cronica valutata con valori recenti di AST o ALT> 1,5 volte il limite superiore normale o bilirubina totale ≥ 1,5 volte il limite superiore normale•paz con malattia linfoproliferativa,o segni o sintomi indicativi di una possibile malattia linfoproliferativa,tra cui linfoadenopatia o splenomegalia,o per patologia maligna primaria o ricorrente,o sono stati in remissione da neoplasia clinicamente significativo per <5 anni• paz esposti a vaccino vivo entro 12 sett precedenti la randomizzazione o che si prevede riceveranno vaccino vivo durante il corso dello studio•paz con infezione batterica, micotica o parassitaria attiva o recente•paz con infezione sintomatica da herpes zoster nelle 12 sett prima dell'ingresso nello studio•paz immunocompromessi da storia di herpes zoster diffuse / complicato•paz allo screening con virus epatite B,virus epatite C o virus immunodeficienza umana•paz con valori dei test di laboratorio fuori dal range di riferimento per la popolazione•paz che allo screening mostrano anomalie all’ECG clinicamente significative•paz con herpes simplex sintomatici al momento dell'ingresso in studio•paz con TBC attiva o latente,positivi a proteina purificata

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients achieving ACR20 (noninferiority of baricitinib monotherapy to MTX monotherapy)

Percentuale di pazienti che hanno raggiunto ACR20 (non inferiorità della monoterapia con baricitinib vs monoterapia con MTX)

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24

Settimana 24

E.5.2

Secondary end point(s)

Endpoint 2:Proportion of patients achieving ACR20 (baricitinib plus MTX compared to MTX monotherapy).Endpoint 3:Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI).Endpoint 4:Change from baseline in DAS28-high-sensitivity C-reactive protein (hsCRP).Endpoint 5:Change from baseline in Modified Total Sharp Score (mTSS [van der Heijde method]).Endpoint 6:AUC of HAQ-DI (baricitinib monotherapy compared to MTX monotherapy).Endpoint 7:AUC of DAS28-hsCRP (baricitinib monotherapy compared to MTX monotherapy).Endpoint 8:Proportion of patients achieving ACR20.Endpoint 9:Proportion of patients achieving ACR50.Endpoint 10:Proportion of patients achieving ACR70 Endpoint 11:Proportion of patients achieving DAS28-hsCRP ≤3.2.Endpoint 12:Proportion of patients achieving DAS28- hsCRP <2.6.Endpoint 13:Proportion of patients achieving DAS28-ESR ≤3.2.Endpoint 14:Proportion of patients achieving DAS28-ESR <2.6

Endpoint 2:Percentuale di pazienti che hanno raggiunto ACR20 (baricitinib più MTX vs monoterapia con MTX). Endpoint 3:Variazione dal basale nell 'indice del questionario HAQ-DI. Endpoint 4:Variazione dal basale del DAS28-alta sensibilità C-reattiva (hs-CRP). Endpoint 5:Variazione rispetto al basale del punteggio mTSS. Endpoint 6: AUC del questionario HAQ-DI (monoterapia baricitinib vs monoterapia con MTX). Endpoint 7: AUC della proteina DAS28 -hs-CRP (monoterapia baricitinib vs monoterapia con MTX) Endpoint 8:Percentuale di pazienti che hanno raggiunto ACR20. Endpoint 9: Percentuale di pazienti che hanno raggiunto ACR50. Endpoint 10:Percentuale di pazienti che hanno raggiunto ACR70 Endpoint 11:Percentuale di pazienti che hanno raggiunto DAS28-hsCRP ≤ 3.2. Endpoint 12:Percentuale di pazienti che hanno raggiunto DAS28-hs-CRP <2.6.Endpoint 13:Percentuale di pazienti che hanno raggiunto DAS28-VES ≤ 3.2.Endpoint 14:Percentuale di pazienti che hanno raggiunto DAS28-VES <2.6

E.5.2.1

Timepoint(s) of evaluation of this end point

Enpoints 2 to 7: Week 24 Enpoint 8: Weeks 12 and 52 Enpoints 9 to 14: Weeks 12, 24 and 52

Endpoint da 2 a 7: settimana 24 Endpoint 8: settimane 12 e 52 Endpoint da 9 a 14: settimane 12, 24, 52

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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)

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

Brazil

Canada

India

Japan

Korea, Republic of

Mexico

Russian Federation

South Africa

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

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

Number of subjects for this age range:

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:

500

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

143

F.4.2.2

In the whole clinical trial

550

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)

Patients who complete this study through week 52 will be eligible to participate in a separate extension study (Study I4V-MC-JADY [JADY]) lasting for up to 2 years if enrollment criteria for Study JADY are met or to the posttreatment follow-up period of this study.

Pazienti che hanno completato questo studio per le 52 settimane saranno elegibili per la patecipazione ad uno studio di estenzione separato (I4V-MC-JADY[JADY]) per i successivi 2 anni se i criteri di arruolamento per lo studio JADY saranno adeguati o ad un posttrattamento di follow up.

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

2013-02-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-18

P. End of Trial
P.	End of Trial Status	Completed

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials