Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42516   clinical trials with a EudraCT protocol, of which   7000   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2011-001729-25
    Sponsor's Protocol Code Number:RA0055
    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:2012-03-19
    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.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2011-001729-25
    A.3Full title of the trial
    A multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of certolizumab pegol in combination with methotrexate for inducing and sustaining clinical response in the treatment of dmard-naïve adults with early active rheumatoid arthritis.
    Studio multicentrico, randomizzato, in doppio cieco, controllato verso placebo sulla sicurezza e sull’efficacia di certolizumab pegol in combinazione con metotrexato per l’induzione e il mantenimento della risposta clinica nel trattamento di soggetti adulti con artrite reumatoide attiva in fase precoce naïve alla terapia con dmard.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study designed to demonstrate the efficacy and safety of certolizumab pegol in combination with Methotrexate in the treatment of subjects suffering from early, progressive active rheumatoid arthritis
    Studio concepito per dimostrare sicurezza ed efficacia di certolizumab pegol in combinazione con metotrexato nel trattamento di soggetti con artrite reumatoide attiva in fase precoce.
    A.4.1Sponsor's protocol code numberRA0055
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUCB PHARMA SA/NV.
    B.1.3.4CountryBelgium
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportUCB Pharma SA
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUCB Biosciences GmbH
    B.5.2Functional name of contact pointCT Registries & Results Disclosure
    B.5.3 Address:
    B.5.3.1Street AddressAlfred Nobel Strasse 10
    B.5.3.2Town/ cityMonheim am Rhein
    B.5.3.3Post code40789
    B.5.3.4CountryGermany
    B.5.4Telephone number+49 2173 48 1515
    B.5.5Fax number+49 2173 48 1572
    B.5.6E-mailclinicaltrials@ucb.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Cimzia
    D.2.1.1.2Name of the Marketing Authorisation holderUCB Pharma SA
    D.2.1.2Country which granted the Marketing AuthorisationBelgium
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCERTOLIZUMAB PEGOL
    D.3.9.1CAS number 428863-50-7
    D.3.9.2Current sponsor codeCDP870
    D.3.9.4EV Substance CodeSUB25423
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Trexan
    D.2.1.1.2Name of the Marketing Authorisation holderOrion Corporation
    D.2.1.2Country which granted the Marketing AuthorisationPoland
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMETHOTREXATE
    D.3.9.1CAS number 59-05-2
    D.3.9.4EV Substance CodeSUB08856MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Early active rheumatoid arthritis
    Artrite reumatoide attiva in fase precoce
    E.1.1.1Medical condition in easily understood language
    Rheumatoid arthritis
    Artrite reumatoide
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10003268
    E.1.2Term Arthritis rheumatoid
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    PERIOD 1 To demonstrate that the combination of CZP + MTX is superior to PBO + MTX in achieving sustained remission by Week 52. PERIOD 2 to demonstrate that both CZP + MTX dosing frequencies (the standard maintenance dose CZP 200mg every 2 weeks + MTX and the reduced frequency maintenance dose CZP 200mg every 4 weeks + MTX) are superior to PBO + MTX in maintaining subjects in LDA at Week 104.
    PERIODO 1: dimostrare la superiorità della combinazione di CZP + MTX rispetto a PBO + MTX nel raggiungere e mantenere la remissione entro la Settimana 52. PERIODO 2: dimostrare che entrambe le frequenze di somministrazione di CZP + MTX (dose di mantenimento standard di CZP 200 mg ogni 2 settimane + MTX e dose di mantenimento a frequenza ridotta di CZP 200 mg ogni 4 settimane + MTX) sono superiori a PBO + MTX nel mantenere la LDA alla Settimana 104.
    E.2.2Secondary objectives of the trial
    PERIOD 1 • To demonstrate that in DMARD-naïve subj. with adult-onset, early active RA present for less than 1 year that the combination therapy of CZP+MTX is superior to PBO+MTX in achieving sustained LDA at W 52 • To compare the efficacy of CZP+MTX to PBO+MTX based on: - Radiographic progression, - Clinical response, - Patient reported outcomes, - Productivity within and outside home PERIOD 2 • To demonstrate that for those subj. achieving sustained remission and treated with CZP+MTX during PER.1, both CZP+MTX dosing frequencies (standard dose /reduced one + MTX) are superior to PBO+MTX in maintaining subj. in remission at 104 weeks. For other objectives please refer to protocol (end of allowed characters).
    PERIODO 1: dimostrare che nei soggetti naïve ai DMARD affetti da AR attiva in fase precoce, con esordio in età adulta, manifestatasi da meno di 1 anno, la terapia di combinazione CZP+MTX è superiore a PBO+MTX nel raggiungere e mantenere la LDA alla Sett 52; Confrontare l’efficacia di CZP+MTX rispetto a PBO MTX in base a: - progressione radiografica; -risposta clinica; - esiti riferiti dal/la paziente; - produttività in ambito domestico e lavorativo. PERIODO 2: dimostrare che, per i soggetti che raggiungono e mantengono la remissione trattati con CZP+MTX durante il Per 1, entrambe le frequenze di somministrazione di CZP+MTX (dose mantenimento standard e a frequenza ridotta + MTX) sono superiori a PBO+MTX nel mantenere la remissione a 104 sett dall’inizio del trattamento. Per gli altri obiettivi si prega di fare riferimento al protocollo (fine caratteri disponibili).
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    OTHER SUBSTUDIES:
    Optional genetics, genomics, proteomics sub-study. Purpose: explore candidate gene expr./DNA biom./candidate blood borne protein biom. relative to risk, prognosis and response to treatm. with CZP.

    ALTRI SOTTOSTUDI:
    Sottostudio opzionale di genomica,genetica e proteomica.Scopo: indagare espress. genica,DNA e biomarcatori proteici a trasm. ematica candidati relativi a rischio,prognosi e risposta al tratt.con CZP

    E.3Principal inclusion criteria
    1. An IRB/ IEC approved written Informed Consent form is signed and dated by the subject prior to any study procedure. 2. To allow collection of blood samples for the genomic, genetic and proteomic analysis the subjects must have signed and dated an IRB/ IEC approved written Pharmacogenomics Informed Consent form. 3. Subject is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, or medication intake according to the judgment of the Investigator. 4. Subject is male or female and must be at least 18 years old at the Screening Visit. 5. Female subjects must be either postmenopausal for at least 1 year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (either oral/parenteral/implantable hormonal contraceptives, intrauterine device or barrier method and spermicide) at Screening. Abstinence only is not an acceptable method. Subjects must agree to use adequate contraception during the study and for at least 10 weeks (or longer if required by local regulations) after the last dose of study treatment. Male subjects must agree to ensure they or their female partner(s) use adequate contraception during the study and for at least 10 weeks (or longer if required by local regulations) after the subject receives their last dose of study treatment. 6. Subjects must have a time since diagnosis of adult-onset RA less than 1 year as defined by the 2010 ACR / EULAR classification criteria from Screening Visit. 7. Subjects must be DMARD-naïve at Screening and Baseline (except antimalarials, see Section 6.2.2 of the protocol). 8. Subjects must have a positive RF or positive ACPA result at Screening. 9. Subjects must have active RA disease as defined in the study protocol.
    1. Il soggetto deve firmare e datare un Modulo di consenso informato scritto approvato dall’IRB/IEC prima di sottoporsi a qualsiasi procedura di studio. 2. Per consentire la raccolta dei campioni di sangue per le analisi genomica, genetica e proteomica il soggetto deve aver firmato e datato un Modulo di consenso informato per le analisi di farmacogenomica approvato dall’IRB/IEC. 3. Secondo il giudizio dello Sperimentatore il soggetto è ritenuto affidabile e in grado di attenersi ai requisiti del protocollo (p. es. è in grado di comprendere e compilare i diari), al programma delle visite e alle istruzioni circa l’assunzione dei farmaci in studio. 4. Sono ammessi soggetti di entrambi i sessi di età &gt;=18 anni al momento della Visita di screening. 5. Allo Screening i soggetti di sesso femminile devono essere in post-menopausa da almeno 1 anno, chirurgicamente sterili o devono utilizzare regolarmente un metodo di contraccezione accettabile (contraccettivi ormonali orali/parenterali/impiantabili, dispositivo intrauterino o metodo di barriera più spermicida). La sola astinenza dai rapporti sessuali non è considerata un metodo accettabile. I soggetti devono acconsentire a praticare una contraccezione adeguata per l’intera durata dello studio e per almeno 10 settimane (o più a lungo, se previsto dalla normativa locale) dopo l’ultima dose di trattamento in studio. I soggetti di sesso maschile devono garantire che la/le loro partner utilizzi/utilizzino metodi di contraccezione adeguati per l’intera durata dello studio e per almeno 10 settimane (o più a lungo, se previsto dalla normativa locale) dalla loro ultima dose di trattamento in studio. 6. Alla Visita di screening i soggetti devono presentare una diagnosi di AR con esordio in età adulta da meno di 1 anno, come definita dai criteri classificativi ACR/EULAR 2010. 7. Allo Screening e al Basale i soggetti devono essere naïve ai DMARD (tranne gli antimalarici, vedere Sezione 6.2.2). 8. Allo Screening i soggetti devono risultare positivi al FR e all’ACPA. 9 I soggetti devono presentare AR attiva come definita in base ai criteri segnalati sul protocollo.
    E.4Principal exclusion criteria
    1. Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study or within 10 weeks following last dose of study drug. 2. The subject has previously participated in this study and has received CZP treatment, or has previously received CZP in or outside of another clinical study. 3. The subject has participated in another study of a medication or a medical device under investigation within the last 3 months or is currently participating in another study of a medication or medical device under investigation. 4. The subject has a known hypersensitivity to any components of CZP or with a history of an adverse reaction to polyethylene glycol (PEG). 5. Subjects must not have a secondary, noninflammatory type of musculoskeletal condition that in the Investigator’s opinion is symptomatic enough to interfere with evaluation of the effect of study drug on the subject’s primary diagnosis of RA. 6. Subjects must not have a diagnosis of any other inflammatory arthritis nor have a Steinbrocker IV functional capacity. 7. Subjects must not have received any experimental nonbiological therapy in the 3 past months or within 5 half-lives prior to Baseline (whichever is longer). 8. Subjects must not have received any experimental or approved biological agent prior to Baseline. 9. Subjects must not have used indicated medications in table 6.1 of the Protocol. 10. Concurrent malignancy or a history of malignancy. 11. Subjects with a history of a lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease. 12. Subjects with a history of blood dyscrasias. 13. Subjects with a current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease or other significant immunological/inflammatory disease including systemic lupus erythematosus, inflammatory bowel disease. 14. Subjects with congestive heart failure as defined by the New York Heart Association 1994 classification criteria. 15. Subjects with a history of, or suspected, demyelinating disease of the central nervous system. 16. Subjects with any other condition which in the Investigator’s judgment would make the subject unsuitable for inclusion in the study. 17. Subject with a value >1.5x ULN for any of the following liver function tests (LFTs) at Screening: • Aspartate aminotransferase (AST) (glutamic oxaloacetic transaminase [GOT]); • Alanine aminotransferase (ALT) (glutamate pyruvate transaminase [GPT]). 18. Subject has history of chronic alcohol or drug abuse within the last 1 year. 19. Subject has any medical or psychiatric condition that, in the opinion of the Investigator, can jeopardize or would compromise the subject’s ability to participate in this study. 20. Subjects with history of or current clinically active infection (including infections verified by chest X-ray) with histoplasma, coccidiodes, paracoccidioides, pneumocystis, nontuberculous mycobacteria, blastomyces, or aspergillus. 21. Subjects with a history of chronic or recurrent infections (>3 episodes requiring antibiotics or antivirals during the preceding year), recent serious or life-threatening infection within the 6 months prior to the Baseline Visit (including herpes zoster), hospitalization for any infection in the last 6 months or any current sign or symptom that may indicate an infection. 22. Subjects at a high risk of infection (eg, leg ulcers, indwelling urinary catheter, and persistent or recurrent chest infections and subjects who are permanently bedridden or wheelchair bound). 23.Subjects with concurrent acute or chronic viral hepatitis B or C. 24.Subjects with known human immunodeficiency virus (HIV) infection. For other excl. crit. please refer to protocol (end of allowed characters)
    1. Pazienti di sesso femminile in allattamento, gravidanza o che pianificano una gravidanza durante lo studio o nelle 10 settimane successive all’ultima dose di farmaco in studio. 2. Precedente partecipazione a questo studio con assunzione di CZP o precedente assunzione di CZP nell’ambito di un altro studio clinico o al di fuori di uno studio clinico. 3. Partecipazione corrente o negli ultimi 3 mesi a un altro studio su un farmaco o un dispositivo medico sperimentale. 4. Ipersensibilità nota a un componente di CZP o storia di reazione avversa a polietilenglicole (PEG). 5. I soggetti non devono presentare un disturbo muscoloscheletrico secondario di tipo non infiammatorio che, nell’opinione dello Sperimentatore, è sufficientemente sintomatico da interferire con la valutazione dell’effetto del farmaco in studio sulla diagnosi primaria di AR del soggetto. 6. I soggetti non devono presentare una diagnosi di altra artrite di tipo infiammatorio né un’abilità funzionale di livello IV secondo il metodo di Steinbrocker. 7. I soggetti non devono aver ricevuto una terapia sperimentale non biologica nei 3 mesi o nelle 5 emivite precedenti il Basale (a seconda di quale periodo sia più lungo). 8. I soggetti non devono aver ricevuto un agente biologico sperimentale o approvato prima del Basale. 9. I soggetti non devono aver usato i farmaci elencati nella tabella 6.1 del protocollo. 10. Neoplasia maligna concomitante o pregressa. 11. Storia di disturbo linfoproliferativo, incluso il linfoma, o segni e sintomi indicativi di malattia linfoproliferativa. 12. Storia di discrasia ematica. 13. Storia recente o corrente, come determinato dallo Sperimentatore, di malattia renale, epatica, ematologica, gastrointestinale, endocrina, polmonare, cardiaca, neurologica o cerebrale grave, progressiva e/o non controllata o di altro disturbo immunologico/infiammatorio significativo, inclusi lupus eritematoso sistemico e infiammazione intestinale. 14. Soggetti con scompenso cardiaco congestizio come definito dai criteri di classificazione della New York Heart Association del 1994. 15. Precedente o sospetta malattia demielinizzante del sistema nervoso centrale. 16. Qualsiasi altra condizione che, nell’opinione dallo Sperimentatore, renderebbe il soggetto non idoneo all’inclusione nello studio. 17. Un valore &gt;1,5 x ULN a uno dei seguenti test di funzionalità epatica effettuati allo Screening: - aspartato aminotransferasi (AST) (glutammato-ossalacetato transaminasi [GOT]); - alanina aminotransferasi (ALT) (glutammato-piruvato transaminasi [GPT]). 18. Storia di abuso cronico di alcol o sostanze nell’ultimo anno. 19. Disturbo medico o psichiatrico che, nell’opinione dello Sperimentatore, può mettere a rischio la sicurezza del soggetto o impedirgli di partecipare a questo studio. 20. Infezione clinicamente attiva pregressa o corrente (incluse le infezioni accertate mediante radiografia del torace) da istoplasma, coccidi, paracoccidi, pneumocisti, micobatteri non tubercolari, blastomiceti o aspergillus. 21. Storia di infezioni croniche o ricorrenti (&gt;3 episodi che hanno richiesto l’uso di antibiotici o antivirali nell’anno precedente), recente infezione grave o potenzialmente fatale nei 6 mesi precedenti la Visita basale (incluso herpes zoster), ospedalizzazione per qualsiasi infezione negli ultimi 6 mesi o eventuali segni e sintomi correnti indicativi di una possibile infezione. 22. Soggetti ad alto rischio di infezione (p. es. ulcere delle gambe, catetere urinario permanente, infezioni al torace persistenti o ricorrenti e soggetti permanentemente allettati o su sedia a rotelle). 23. Infezione concomitante cronica o acuta da virus dell’epatite B o C. 24. Infezione nota da virus dell’immunodeficienza umana (HIV). Per gli altri criteri di esclusione si prega di fare riferimento al protocollo (fine caratteri disponibili).
    E.5 End points
    E.5.1Primary end point(s)
    PERIOD 1: 1) proportion of subjects in sustained remission (defined as DAS28[ESR] <2.6 at Week 40 and Week 52 visits) PERIOD 2: 2) proportion of subjects who maintain LDA (DAS28[ESR] ≤3.2) from Week 52 through Week 104 without flaring.
    PERIODO 1: 1) percentuale di soggetti che mantengono la remissione (definita come un punteggio DAS28 [basato sulla VES] <2,6 alle visite della Settimana 40 e della Settimana 52). PERIODO 2: 2) percentuale di soggetti che mantengono la LDA (DAS28 [basato sulla VES] <=3,2) dalla Settimana 52 alla Settimana 104 senza sviluppare esacerbazioni.
    E.5.1.1Timepoint(s) of evaluation of this end point
    1) Week 52; 2) Week 52 through Week 104.
    1) Settimana 52; 2) dalla Settimana 52 alla Settimana 104.
    E.5.2Secondary end point(s)
    PERIOD 1: 1) proportion of subjects in sustained LDA (defined as DAS28[ESR] ≤3.2 at Week 40 and Week 52 visits). 2) Radiographic variables: • change in the van der Heijde modified total sharp score (mTSS), • proportion of subjects with radiographic nonprogression, defined as change in mTSS ≤ 0.5; • change in joint erosion score; • change in joint narrowing score. 3) Clinical variables: • American College of Rheumatology (ACR)20, ACR50, ACR70 response rates in relation to Baseline, • proportion of subjects achieving a good or moderate EULAR clinical response (according to the DAS28(ESR)-based EULAR response criteria), • changes from Baseline in individual components of the ACR criteria, including tender joint count (TJC), swollen joint count (SJC), Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient Assessment of Arthritis Pain-Visual Analog Scale (PtAAP), Patient Global Assessment of Disease Activity (PtGADA), Physician Global Assessment of Disease Activity (PhGADA), CRP (ratio to Week 0) and erythrocyte sedimentation rate (ESR, ratio to Week 0), • changes from Baseline in DAS28(ESR), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI), • proportion of subjects in remission as defined by: - the new ACR/EULAR 2011 remission criteria (TJC ≤1, SJC ≤1, CRP ≤1mg/dl and PtGADA ≤1); - the new ACR/EULAR 2011 remission criteria simplified for clinical practice (TJC ≤1, SJC ≤ 1 and PtGADA ≤1); - DAS28(ESR) <2.6;- CDAI ≤2.8; - SDAI ≤3.3. 4) Patient-reported variables: • proportion of subjects reaching normative physical function (HAQ-DI score ≤0.5), • change from Baseline in Bristol RA Fatigue Multidimensional Questionnaire (BRAF–MDQ) total, • scores of the individual questions of the Work Productivity Survey RA (WPS-RA). PERIOD 2: 5) the proportion of subjects who are in sustained remission at Week 52 and maintain their remission (DAS28[ESR] <2.6) from Week 52 through Week 104 without flaring. 6) Radiographic variables: • change in the van der Heijde modified total sharp score (mTSS), • proportion of subjects with radiographic nonprogression, defined as change in mTSS ≤ 0.5, • change in joint erosion score, • change in joint narrowing score. 7) Clinical variables: • ACR20, ACR50, ACR70 response rates in relation at Week 0, • proportion of subjects achieving a good or moderate EULAR clinical response (according to the DAS28[ESR]-based EULAR response criteria), • changes from Week 0 and from Week 52 in individual components of the ACR criteria, including TJC, SJC, HAQ-DI, PtAAP, PtGADA, PhGADA, CRP (ratio to Week 0) and ESR (ratio to Week 0), • changes from Week 0 and from Week 52 in DAS28(ESR), CDAI and SDAI. (…) (for other clinical variables related to this secondary endpoint please refer to protocol: end of allowed characters) 8) Patient-reported variables: • proportion of subjects reaching normative physical function (HAQ-DI score ≤0.5), • change from Week 0 in BRAF–MDQ total, • scores of the individual questions of the Work Productivity Survey RA (WPS-RA).
    PERIODO 1: 1) percentuale di soggetti con LDA stabile (definita come un punteggio DAS28 [basato sulla VES] <=3,2 alle visite della Settimana 40 e della Settimana 52). 2) Variabili radiografiche: - variazione nel punteggio van der Heijde-mTSS (Total Sharp Score modificato); - percentuale di soggetti che non presentano progressione radiografica, definita come una variazione nel punteggio mTSS <=0,5; - variazione nel punteggio relativo all’erosione articolare; - variazione nel punteggio relativo all’assottigliamento articolare. 3) Variabili cliniche: - tassi di risposta ACR (American College of Rheumatology)20, ACR50 e ACR70 rispetto al Basale; - percentuale di soggetti che raggiungono una risposta clinica EULAR buona o moderata (in base ai criteri di risposta EULAR secondo il punteggio DAS28 [basato sulla VES]); - variazioni rispetto al Basale nelle singole componenti dei criteri ACR, inclusi la conta delle articolazioni dolenti (TJC), la conta della articolazioni gonfie (SJC), il questionario HAQ-DI (Health Assessment Questionnaire-Disability Index), la Scala analogica visiva PtAAP (Patient Assessment of Arthritis Pain), l’indice PtGADA (Patient Global Assessment of Disease Activity), l’indice PhGADA (Physician Global Assessment of Disease Activity, la PCR (rispetto alla Settimana 0) e la velocità di eritrosedimentazione (VES, rispetto alla Settimana 0); - variazioni rispetto al Basale nel punteggio DAS28 (basato sulla VES), nell’indice CDAI (Clinical Disease Activity Index) e nell’indice SDAI (Simplified Disease Activity Index); - percentuale di soggetti in remissione in base ai criteri seguenti: i nuovi criteri di remissione ACR/EULAR 2011 (TJC <=1, SJC <=1, PCR <=1 mg/dL e PtGADA <=1); i nuovi criteri di remissione ACR/EULAR 2011 semplificati per la pratica clinica (TJC <=1, SJC <=1 e PtGADA <=1); DAS28 (basato sulla VES) <2,6; CDAI <=2,8; SDAI <=3,3. 4) Variabili riferite dal/la paziente: percentuale di soggetti che raggiungono la normale funzionalità fisica (punteggio HAQ-DI <=0,5); variazione rispetto al basale nel punteggio totale del questionario BRAF-MDQ (Bristol RA Fatigue Multidimensional Questionnaire); punteggi alle singole domande del questionario WPS-RA (Work Productivity Survey RA). PERIODO 2: 5) percentuale di soggetti che mantengono la LDA (DAS28 [basato sulla VES] ≤3,2) dalla Settimana 52 alla Settimana 104 senza sviluppare esacerbazioni. 6) Variabili radiografiche: - variazione nel punteggio van der Heijde-mTSS; - percentuale di soggetti che non presentano progressione radiografica, definita come una variazione nel punteggio mTSS <=0,5; - variazione nel punteggio relativo all’erosione articolare; - variazione nel punteggio relativo all’assottigliamento articolare. 7) Variabili cliniche: - tassi di risposta ACR20, ACR50 e ACR70 rispetto al Basale; - percentuale di soggetti che raggiungono una risposta clinica EULAR buona o moderata (in base ai criteri di risposta EULAR secondo il punteggio DAS28 [basato sulla VES]); - variazioni dalla Settimana 0 e dalla Settimana 52 nelle singole componenti dei criteri ACR, inclusi TJC, SJC, questionario HAQ-DI, scala PtAAP, indici PtGADA e PhGADA, PCR (rispetto alla settimana 0) e VES (rispetto alla Settimana 0); - variazioni dalla Settimana 0 e dalla Settimana 52 nel punteggio DAS28 (basato sulla VES) e agli indici CDAI e SDAI (…) (per le altre variabili cliniche relative a questo endpoint secondario si prega di fare riferimento al protocollo: fine caratteri disponibili). 8) Variabili riferite dal/la paziente: percentuale di soggetti che raggiungono la normale funzionalità fisica (punteggio HAQ-DI <=0,5); variazione dalla Settimana 0 nel punteggio totale del questionario BRAF-MDQ; punteggi alle singole domande del questionario WPS-RA (Work Productivity Survey RA).
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) Week 52; 2) Baseline-Week 52; 3) Week 12-24-52/withdrawal visit; 4) Week 12-24-52/withdrawal visit; 5) Week 52 through Week 104; 6) Week 0 to Week 104/withdrawal visit or Week 52 to Week 104/withdrawal visit; 7) Week 104/withdrawal visit; 8) Week 104/withdrawal visit.
    1) Settimana 52; 2) Basale-Settimana 52; 3) Settimana 12-24-52/visita di ritiro; 4) Settimana 12-24-52/visita di ritiro; 5) da Settimana 52 a Settimana 104; 6) da Settimana 0 a Settimana 104/visita di ritiro o da Settimana 52 a Settimana 104/visita di ritiro; 7)Settimana 104/visita di ritiro; 8) Settimana 104/visita di ritiro.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA106
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Australia
    Brazil
    Canada
    Colombia
    Mexico
    Switzerland
    Turkey
    United States
    E.8.7Trial has a data monitoring committee No
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months54
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months54
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 400
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 400
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state70
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 350
    F.4.2.2In the whole clinical trial 800
    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)
    Standard care
    Normale pratica clinica
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-05-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-03-05
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-09-10
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA