Clinical Trials Register

Summary
EudraCT Number:	2007-001625-10
Sponsor's Protocol Code Number:	0881X1-4437(Amendment1,19March2008)
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2009-04-01
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

2007-001625-10

A.3

Full title of the trial

An Open-Label, Randomized Study to Evaluate the Radiographic Efficacy and Safety of Enbrel™ (Etanercept) added to Methotrexate in Comparison with Usual Treatment in Subjects with Moderate Rheumatoid Arthritis Disease Activity.

An Open-Label, Randomized Study to Evaluate the Radiographic Efficacy and Safety of Enbrel (Etanercept) added to Methotrexate in Comparison with Usual Treatment in Subjects with Moderate Rheumatoid Arthritis Disease Activity.

A.3.2

Name or abbreviated title of the trial where available

EXTRA

A.4.1

Sponsor's protocol code number

0881X1-4437(Amendment1,19March2008)

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	Wyeth Pharmaceuticals France
B.1.3.4	Country	France
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	ENBREL
D.2.1.1.2	Name of the Marketing Authorisation holder	WYETH LEDERLE SpA
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.3.4	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	185243690
D.3.9.2	Current sponsor code	WAY-143050
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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	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

Rheumatoid Arthritis

Artrite Reumatoide

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

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

To evaluate the impact of ETN + MTX in comparison with usual treatment on radiographic disease progression at 52 weeks in subjects with moderate RA who failed treatment with MTX.

Valutare l'effetto di ETN 50 mg una volta alla settimana in associazione a MTX in confronto con il trattamento standard sulla progressione radiografica di malattia a 52 settimane in soggetti con RA moderata che non hanno risposto al trattamento con MTX.

E.2.2

Secondary objectives of the trial

•To compare the effects of ETN + MTX and usual treatment on clinical outcomes •To compare the effects of ETN + MTX and usual treatment on health-related quality of life and dimensions of impact of disease on subjects over 52 weeks. •To evaluate the safety of the treatment regimen over 52 weeks.

•Confrontare gli effetti di ETN 50 mg una volta alla settimana in associazione a MTX sui risultati clinici.•Confrontare gli effetti di ETN 50 mg volta alla settimana in associazione a MTX sulla qualita' di vita e sulla dimensione dell'impatto della malattia sui soggetti per 52 settimane.•Valutare la sicurezza del regime di trattamento per 52 settimane.

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

ALTRI SOTTOSTUDI:
Titolo: Proprieta' psicometriche della sinovite misurata con l'ultrasonografia nell'artrite reumatoide: uno studio ancillare di 'etarnecept versus DMARDs' nell'AR moderata
Data Versione: 09/01/2008

E.3

Principal inclusion criteria

¿18 years of age or older at time of consent. ¿Meet the 1987 ACR Revised Criteria for Rheumatoid Arthritis. ¿Active Rheumatoid Arthritis: evidence of clinical signs of joint inflammation / swelling at screening and randomization. ¿Documented evidence, confirmed by a blinded 3rd party assessor, of at least one erosion observed by X-ray (hands or feet) at randomization based on X-ray taken at the screening visit. Subjects with no confirmed erosion at the randomization visit are to be withdrawn. ¿¿ Plasma C-reactive protein level of at least 8.0 mg/L or Erythrocyte Sedimentation Rate of at least 28 mm/h in sample taken at the screening visit. ¿¿ Currently receiving optimized* treatment with MTX but with active disease as defined by a DAS28 score of >3.20 and ≤<5.10 at both the screening and randomization visits. The erythrocyte sedimentation rate (ESR) value at the screening visit will be used for the DAS 28 calculation at the randomization visit * Have received MTX orally, intramuscularly or SC for at least 4 months before screening with at least 2 months at the highest tolerated dose (not less than 12.5mg/week). ¿Functional status Class I, II or III as defined by ACR Revised Criteria. ¿Onset of disease after 16 years of age. ¿In the opinion of the investigator, the subject will be able to comply with the requirements of the protocol, including ability to present for all required visits. ¿Capable of understanding and willing to provide signed and dated written, voluntary informed consent before any protocol-specific procedures are performed. ¿Able and willing to self-inject study drug or have a designee who can do so. ¿Able and willing to take oral medication.

¿Eta` minima di 18 anni compiuti al momento della firma del consenso. ¿Pazienti che soddisfino gli ACR Revised Criteria for Rheumatoid Arthritis - 1987. ¿Artrite Reumatoide attiva: evidenza di segni clinici di infiammazione/rigonfiamento articolare allo screening e alla randomizzazione. ¿Evidenza documentata, confermata da una terza parte in cieco, di almeno una erosione osservata attraverso i raggi X (mani o piedi) alla visita di randomizzazione, basandosi sulle radiografie effettuate alla visita di screening. I soggetti che non presentino erosioni confermate alla visita di randomizzazione, saranno discontinuati. ¿ Livelli di proteina C-reattiva nel plasma di almeno 8.0 mg/L nel campione prelevato alla visita di screening o velocita` di sedimentazione della emazie di almeno 28 mm/ora.. ¿ Pazienti che stiano ricevendo un trattamento ottimizzato* con MTX ma con una malattia attiva, definita mediante un valore di DAS28 >3.20 e <5.10 sia alla visita di screening che alla visita di randomizzazione. La velocita` di sedimentazione eritrocitaria (ESR) alla visita di screening sara` utilizzata per il calcolo di DAS28 alla visita di randomizzazione. * Abbiano ricevuto MTX orale, intramuscolo o SC per almeno 4 mesi prima dello screening, con almeno 2 mesi alla dose massima tollerata (non meno di 12.5 mg/settimana). ¿Pazienti che abbiano ricevuto MTX ad una dose stabile nei 28 giorni precedenti lo screening. ¿Pazienti che, secondo il parere dello sperimentatore, possano continuare il trattamento con MTX ad una dose di 12.5 mg/settimana o superiore, ma comunque non superiore a 25 mg/settimana. ¿Stato funzionale di Classe I, II o III definito secondo gli ACR Revised Criteria ¿Comparsa della malattia dopo i 16 anni di eta`. ¿A discrezione dello sperimentatore, il soggetto sia in grado di attenersi alle richieste del protocollo, inclusa la capacita` di presentarsi a tutte le visite richieste. ¿Il soggetto sia in grado di capire e di firmare volontariamente un consenso informato prima che qualsiasi procedura dello studio sia avviata. ¿Il soggetto sia in grado di auto iniettarsi ETN o abbia qualcuno che lo possa fare. ¿Il soggetto sia in grado di assumere una terapia orale.

E.4

Principal exclusion criteria

¿Previous treatment with ETN, infliximab, adalimumab, other TNF-alfa inhibitors, anakinra or other biological agents. ¿Receipt of any DMARD, other than MTX, within 28 days before screening. ¿Unable to tolerate MTX at a minimum dose of 12.5 mg/week orally, intramuscularly or SC. ¿Known significant (in the opinion of the investigator) concurrent medical disease including: ¿Uncompensated congestive heart failure, or class III or IV heart failure defined by the New York Heart Association classification. ¿History of or current pancytopenia or aplastic anemia. ¿Diagnosis of multiple sclerosis or other central or peripheral nervous system demyelinating diseases. ¿Current malignancy or an individual history of cancer (other than resected basal cell carcinoma of the skin) within five years of the screening visit. ¿Active infection including known human immunodeficiency virus (HIV) infection and tuberculosis (TB) (Note: follow local country guidelines for appropriate screening and treatment of tuberculosis in the setting of anti-TNF therapy). ¿Sepsis, or at risk of sepsis. ¿Subjects with signs of immunodeficiency. ¿Other current autoimmune connective tissue diseases such as diagnosis of systemic lupus erythematosus, scleroderma, or polymyositis. ¿Significant renal disease in the investigator¿s opinion ¿Abnormal hematology or chemistry profiles: ¿white blood cell (WBC) count < o = 3.5 x 109/L ¿ Hemoglobin level < o = 85 g/L or 5.3 mmol/L ¿ Hematocrit < o = 27%. ¿ Platelet count < o = 125 x 109/L ¿ Serum creatinine level > o = 175 umol/L ¿ Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > o = 2 times the laboratory¿s upper limit of normal ¿ Clinically significant abnormal screening laboratory values in the investigator¿s opinion (based on country-specific standard of care) ¿ Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception. ¿ Use of any investigational treatment or device within 3 months (or 5 half lives of the treatment, whichever is longer) of the screening visit. ¿ Concomitant oral corticosteroid >10 mg/day of prednisone or its equivalent at the point of screening (corticosteroid dose must be stable for at least 4 weeks prior to screening). ¿ Intra-articular, intravenous, intramuscular or subcutaneous (SC) corticosteroid injection within 28 days of the screening visit. ¿ Active alcoholism and/or substance abuse within one year of the screening visit. ¿Conditions requiring initiation of new drug therapy concurrent with entry into this study.

¿Precedente trattamento con ETN, infliximab, adalimumab, altri inibitori del TNF-alfa, anakinra o altri agenti biologici. ¿Assunzione di qualsiasi DMARD, ad eccezione di MTX, entro 28 giorni dallo screening. ¿Incapace di tollerare MTX alla dose minima di 12.5 mg/settimana orale, intramuscolare o SC. ¿Malattie concomitanti conosciute e significative (a discrezione dello sperimentatore), comprese: ¿Scompenso cardiaco congestizio o scompenso cardiaco di classe III o IV, secondo la classificazione del New York Heart Association ¿Pancitopenia o anemia aplastica pregresse o concomitanti. ¿Diagnosi di sclerosi multipla o altre malattie demielinizzanti del sistema nervoso centrale o periferico. ¿Storia individuale di cancro entro cinque anni dalla visita di screening o altri tumori maligni concomitanti (ad eccezione di carcinoma della pelle a cellule basali precedentemente asportato). ¿Infezioni attive, incluso virus da immunodeficienza (HIV) conosciuto e tubercolosi (TB) (nota: seguire le linee guida locali per lo screening e il trattamento della tubercolosi nella terapia con anti-TNF). ¿Sepsi o rischio di sepsi. ¿Soggetti con segni di immunodeficienza. ¿Altre malattie autoimmuni concomitanti del tessuto connettivo, come il lupus eritematoso sistemico, sclerodermia o polimiosite. ¿Malattia renale significativa secondo l¿opinione dello sperimentatore. ¿Profilo di ematologia o biochimica anormali: ¿Globuli bianchi (WBC) < o = 3.5 x 109/L ¿Emoglobina < o = 85 g/L o 5.3 mmol/L ¿ Ematocrito < o = 27%. ¿ Conta delle piastrine < o = 125 x 109/L ¿ Creatinina Serica > o = 175 umol/L ¿ Aspartato aminotransferasi (AST) o alanina aminotransferasi (ALT) > o = 2 volte il limite superiore di normalita` ¿ Valori anormali di laboratorio alla visita di screening e considerati dallo sperimentatore clinicamente significativi (secondo gli standard di riferimento del paese in questione). ¿ Donne in gravidanza, che stiano allattando o a rischio di gravidanza e che non stiano usando un metodo accettabile di contraccezione. ¿ Uso di qualsiasi trattamento o dispositivo sperimentale entro 3 mesi dalla visita di screening (o entro 5 emivite del farmaco, a seconda di quale sia piu` lunga). ¿ Assunzione concomitante di corticosteroidi orali ad una dose > di 10 mg/giorno di prednisone o suoi equivalenti al momento dello screening (la dose di corticosteroidi deve essere stabile da almeno 4 settimane prima dello screening). ¿ Iniezione di corticosteroidi intra-articolare, endovena, intramuscolo o sottocute (SC) nei 28 giorni precedenti la visita di screening. ¿ Alcolismo attivo e/o assunzione di sostanze di abuso entro un anno dalla visita di screening. ¿ Condizioni che richiedano l¿inizio di una nuova terapia farmacologica concomitante con l¿ingresso in studio.

E.5 End points

E.5.1

Primary end point(s)

Change from randomization in modified Total Sharp Score (TSS) at 52 weeks.

Variazione del TSS nel periodo intercorrente dalla randomizzazione a 52 settimane.

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

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

100

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

E.8.7

Trial has a data monitoring committee

E.8.8

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

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	No
F.1.1	Number of subjects for this age range:	0
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2009-04-01.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	70
F.4.2	For a multinational trial
F.4.2.1	In the EEA	639
F.4.2.2	In the whole clinical trial	700

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

2008-09-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-11-26

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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