| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderately to severely active rheumatoid arthritis |
| artrite reumatoide da moderatamente a gravemente attiva |
|
| E.1.1.1 | Medical condition in easily understood language |
| Rheumatoid arthritis |
| Artrite Reumatoride |
|
| 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 | 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 | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to evaluate the effects of filgotinib versus placebo for the treatment of signs and symptoms of rheumatoid arthritis (RA) as measured by the proportion of subjects achieving an American College of Rheumatology 20% improvement response (ACR20) at Week 12 |
| Valutare gli effetti di filgotinib rispetto al placebo per il trattamento dei segni e dei sintomi dell'artrite reumatoide (AR), misurati dalla proporzione di soggetti che raggiungono una risposta di miglioramento del 20% secondo l'American College of Rheumatology (ACR20) alla Settimana 12 |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the effects of filgotinib versus placebo as measured by the proportion of subjects achieving Disease Activity Score for 28 joint count using c-reactive protein (DAS28[CRP]) =3.2 at Week 12
- To evaluate the effect of filgotinib versus placebo on physical function as measured by change from Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) score at Week 12
- To evaluate the effects of filgotinib versus placebo for the treatment of signs and symptoms of RA as measured by the proportion of subjects achieving DAS28 (CRP)<2.6 at Week 24
- To evaluate the effects of filgotinib versus placebo on preservation of joint structure as measured by change from Baseline in the van der Heijde modified Total Sharp Score (mTSS) at Week 24
- To evaluate the effects of filgotinib versus adalimumab for the treatment of signs and symptoms of RA as measured by the proportion
of subjects achieving DAS28 (CRP) = 3.2 at Week 12 |
- Valutare gli effetti di filgotinib rispetto al placebo, misurati in base alla percentuale di soggetti che raggiungono un punteggio di attivit¿ della malattia (Disease Activity Score, DAS) per la conta di 28 articolazioni utilizzando la proteina C-reattiva (DAS28[CRP]) =3.2 alla Settimana 12
- Valutare l¿effetto di filgotinib rispetto al placebo sulla funzione fisica, misurato in base alla variazione rispetto al Basale nel punteggio dell¿Indice di disabilit¿ valutato attraverso il Questionario di valutazione dello stato di salute (HAQ-DI) alla Settimana 12
- Valutare gli effetti di filgotinib rispetto al placebo nel trattamento di segni e sintomi di AR, misurati in base alla percentuale di soggetti che ottengono un DAS28 (CRP) <2.6 alla Settimana 24
- Valutare gli effetti di filgotinib rispetto al placebo sulla conservazione della struttura articolare, misurata in base alla variazione rispetto al Basale nel punteggio totale di Sharp modificato da van der Heijde (mTSS) alla Settimana 2 |
|
| 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 types of substudies
Specify title, date and version of each substudy with relative objectives: Optional MRI sub-study: At selected sites, a subset of subjects may consent to participate in an optional MRI substudy (see Section 3.9). For those subjects, an MRI of a single hand and wrist will be performed postrandomization within 7 days of the first dose and repeated at Week 12. Hand and wrist of each subject will be imaged using a 1.5 Tesla or 3 Tesla whole-body MRI scanner. Images will be centrally read by 2
radiologists who are blinded with regard to visit sequence, subject treatment assignment and
the alternate reader's scores.
|
Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Sottostudio opzionale di risonanza magnetica (RM)
In centri selezionati, un sottoinsieme di soggetti avr¿ facolt¿ di partecipare a un sottostudio opzionale di RM (vedere Sezione 3.9). Per tali soggetti, una RM di una singola mano e di un singolo polso saranno eseguiti dopo la randomizzazione entro 7 giorni dalla prima dose e ripetuti alla Settimana 12. Le immagini della mano e del polso di ciascun soggetto saranno acquisite mediante scanner RM del corpo intero a 1.5 Tesla o a 3 Tesla. Le immagini saranno lette centralmente da 2 radiologi in cieco rispetto alla sequenza delle visite, all¿assegnazione dei soggetti al trattamento e ai punteggi dell¿altro lettore.
|
|
| E.3 | Principal inclusion criteria |
For a complete list of study inclusion criteria, please refer to study
protocol (sections 4.2):
1) Male or female subjects who are =18 years of age, on the day of signing informed consent.
2) Have a diagnosis of RA (2010 ACR/EULAR criteria for RA), and are ACR functional class I-III .
3) Have =6 swollen joints (from a SJC66) and =6 tender joints (from a TJC68) at both Screening and Day 1 (need not be the same joints).
4) Must meet at least one of the Screening parameters defined in the protocol (section 4.2) regarding the number of joint erosions and serum CRP
5) Ongoing treatment with a stable dose of MTX as described in the protocol (section 4.2)
6) Females of childbearing potential must have a negative pregnancy test at screening and Day 1
7) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified
method(s) of contraception.
8) Lactating female subjects must agree to discontinue nursing from Screening through the end of their study participation.
9) Meet one of the tuberculosis (TB) Screening criteria described in the protocol (section 4.2)
10) Able and willing to sign the informed consent as approved by the Independent Ethics Committee (IEC)/Institutional Review Board (IRB).
Written consent must be provided before initiating any screening
evaluations. Subjects must have read and understood the informed
consent form (ICF), must fully understand the requirements of the
study, and must be willing to comply with all study visits and
assessments; subjects who cannot read or
understand the ICF may not be enrolled by a guardian or any other
individual.
11) Able and willing to perform subcutaneous self-injections or have a
caregiver able, willing and available to administer the injections.
12) Subjects receiving non-prohibited medication for any reason should be on a stable dose (defined as no change in prescription) within 7 days
or 5 half-lives (whichever is longer) prior to the first administration of study drug on Day 1. |
Principali criteri di eleggibilità
1) Soggetti di sesso maschile o femminile con = 18 anni di età alla data della firma del consenso informato.
2) Avere una diagnosi di AR (criteri ACR 2010/EULAR) ed essere di classe funzionale ACR I-III.
3) Avere =6 articolazioni tumefatte (da una SJC66) e =6 articolazioni dolenti (da una TJC68) allo Screening e al Giorno 1.
4) Deve risultare soddisfatto almeno uno dei seguenti parametri allo Screening: a) =1 erosione articolare documentata all’esame radiografico di mani, polsi o piedi in base alla lettura centrale E positività ad anti-CCP o FR al laboratorio centrale
OPPURE
b) Avere =3 erosioni documentate all’esame radiografico di mani, polsi o piedi in base alla lettura centrale se entrambi gli anticorpi (ad es. RF, anti-CCP) risultano negativi (in base al laboratorio centrale),
OPPURE
c) CRP sierica = 6 mg/l in base al valore calcolato dal laboratorio centrale
5) Trattamento continuo con una dose stabile di MTX secondo quanto descritto di seguito:
a) Uso continuo di MTX orale da almeno 12 settimane prima del Giorno 1 e a una dose stabile prescritta di 7.5-25 mg/settimana da almeno 4 settimane prima del Giorno 1. Dosi stabili <7.5 mg/settimana sono consentite unicamente in presenza di intolleranza o tossicità a dosi superiori ovvero laddove dosi maggiori siano proibite dall’etichetta locale o dalla pratica clinica locale. Dosi settimanali >25 mg non sono ammesse durante lo studio.
b) I soggetti dovranno ricevere una dose stabile adeguata e prescritta di acido folico (dose totale =5 mg/settimana o secondo la pratica clinica locale), che dovrà essere verificata o avviata allo Screening e proseguita per l’intera durata dello studio.
c) I soggetti potranno utilizzare idrossiclorochina (HCQ) =400 mg/die o clorochina =250 mg/die concomitanti durante lo studio, purché la prescrizione sia stabile da almeno 4 settimane prima del Giorno 1.
6) I soggetti che hanno fallito la precedente terapia con un bDMARD non sono idonei alla partecipazione. I soggetti con precedente esposizione a uno bDMARD potranno essere arruolati (circa il 20% della popolazione totale dello studio), se vi è evidenza documentata di esposizione limitata (ovvero inferiore ai 3 mesi) a bDMARD
|
|
| E.4 | Principal exclusion criteria |
For a complete list of study exclusion criteria, please refer to study protocol (Sections 4.3):
1) Prior treatments for RA as defined in Section 4.3 of the protocol
2) Known hypersensitivity or allergy to the study drug(s), its metabolites, or formulation excipients.
3) Oral steroids at a dose >10 mg/day of prednisone (or equivalent) or a prescription for oral steroids which has changed within 4 weeks of Day 1.
4) Receipt of an intra-articular or parenteral corticosteroid injection within 4 weeks prior to Day 1.
5) Use of nonsteroidal anti-inflammatory drugs (NSAIDs) which have not
been at a stable dose (defined as no change in prescription) for at least 2 weeks prior to Day 1. NOTE: subjects are permitted to take acetylsalicylic acid at a dose of =325mg daily for cardiac prophylaxis, or occasional NSAIDs for non-RA indications (eg, headache).
6) Administration of a live/attenuated vaccine within 30 days prior to Day 1, or planned during the study.
7) Participation in any clinical study of an investigational drug/device within 4 weeks or 5 half-lives prior to Screening, whichever is longer. Exposure to investigational biologics should be discussed with the Sponsor.
8) Have undergone surgical treatments for RA, including synovectomy or arthroplasty in >4 joints
9) Have any chronic, uncontrolled medical condition, which would put the subject at increased risk during study participation, such as uncontrolled: diabetes, hypertension, morbid obesity, thyroid, adrenal, pulmonary, hepatic, renal, neurologic or psychiatric disease, or other Disease of concern, as per judgment of investigator
10) Have a history of major surgery (requiring regional block or general anesthesia) within the last 3 months prior to Screening or planned major surgery during the study.
11) Have a moderately to severely active, generalized musculoskeletal disorder that would interfere with assessment of study parameters or increase risk to the subject by participating in the study.
12) Active autoimmune disease that would interfere with assessment of study parameters or increase risk to the subject by participating in the study.
13) History of or current moderate to severe congestive heart failure (New York Heart Association [NYHA] class III or IV), or within the last 6 months, a cerebrovascular accident, myocardial infarction, unstable angina, unstable arrhythmia, new or significant ECG finding at Screening, or any other cardiovascular condition which, in the opinion of the investigator, would put the subject at risk by participation in the study.
14) History of malignancy within the past 5 years prior to Screening
15) History of lymphoproliferative disease or current lymphoproliferative disease
16) History of gastrointestinal perforation.
17) History of organ or bone marrow transplant.
18) Positive serology for human immunodeficiency virus (HIV) 1 or 2.
19) Evidence of active Hepatitis C Virus (HCV) infection.
20) Evidence of active Hepatitis B Virus (HBV) infection.
21) History of opportunistic infection, or immunodeficiency syndrome, which would put the subject at risk, as per investigator judgment.
22) Active infection that is clinically significant, as per judgment of the investigator, or any infection requiring hospitalization or treatment with intravenous anti-infectives within 60 days of Screening; or any infection requiring oral anti-infective therapy within 30 days of Screening.
23) Currently on any therapy for chronic infection. Past history of disseminated Staphylococcus aureus or disseminated Herpes simplex infection.
24) History of symptomatic herpes zoster infection within 12 weeks prior to Screening or have history of disseminated/complicated herpes zoster infection.
25) History of an infected joint prosthesis or other implanted device with retention of the prosthesis or device in situ.
26) Current drug, tobacco or alcohol abuse, per investigator judgement.
27) Any known condition or contraindication as addressed in the local labeling for adalimumab and/or MTX that would preclude the subject from participating in this study.
28) Any condition including active fibromyalgia that based on the investigator's opinion would make it difficult to appropriately assess RA activity for the purposes of this study.
29) Any condition or circumstances which in the opinion of the Investigator or Sponsor may make a subject unlikely or unable to complete the study or comply with study procedures and requirements.
30) Use of prohibited medication as outlined in section 5.5
31) Significant blood loss (>450 mL) or transfusion of any blood product within 12 weeks prior to Day 1.
32) Tests performed at the central laboratory at Screening as defined in study protocol (Section 4.3) |
| Per l’elenco completo dei criteri di esclusione si rimanda alle Sezione 4.3. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Week 12 |
| L’endpoint primario è la percentuale di soggetti che ottengono una risposta ACR20 alla Settimana 12 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The primary endpoint for this study is the proportion of subjects who achieve an ACR20 response at Week 12 |
| Settimana 12 |
|
| E.5.2 | Secondary end point(s) |
- The proportion of subjects who achieve DAS28 (CRP)=3.2 at Week 12
- Change from Baseline in the HAQ-DI score at Week 12
- The proportion of subjects who achieve DAS28 (CRP)<2.6 at Week 24
- Change from Baseline in mTSS at Week 24 |
- Percentuale di soggetti che ottengono un DAS28 (CRP) =3.2 alla Settimana 12
- Variazione rispetto al Basale nel punteggio HAQ-DI alla Settimana 12
- Percentuale di soggetti che ottengono un DAS28 (CRP) =2.6 alla Settimana 24
- Variazione rispetto al Basale nel mTSS alla Settimana 24 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Week 12 and Week 24 |
| Settimana 12 e settimana 24 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 70 |
| 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 | Information not present in EudraCT |
| 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 |
| Australia |
| Brazil |
| Canada |
| Chile |
| Colombia |
| Hong Kong |
| India |
| Israel |
| Korea, Republic of |
| Malaysia |
| Mexico |
| New Zealand |
| Peru |
| Russian Federation |
| Serbia |
| South Africa |
| Taiwan |
| Thailand |
| Ukraine |
| United States |
| Belgium |
| France |
| Germany |
| Hungary |
| Ireland |
| Italy |
| Romania |
| Slovakia |
| Spain |
| Switzerland |
| United Kingdom |
| Czechia |
| Argentina |
|
| 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
|
| End of Study is defined as when the last subject has completed 52 weeks of dosing plus the 4 week post treatment visit or has entered the long term extension study (GS-US-417-0304) |
| La conclusione della sperimentazione avviene quando l'ultimo soggetto ha completato le 52 settimane di trattamento e la visita di post trattamento a 4 settimane o ¿ entrato nello studio di estensione a lungo termine (GS-US-417-0304) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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