E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid arthritis |
Artrite reumatoide |
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E.1.1.1 | Medical condition in easily understood language |
Rheumatoid arthritis |
Artrite reumatoide |
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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 | 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 |
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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 the study is to evaluate the long-term safety and tolerability of baricitinib.
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L'obiettivo primario dello studio è valutare la sicurezza e la tollerabilità a lungo termine di baricitinib nei pazienti affetti da artrite reumatoide. |
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E.2.2 | Secondary objectives of the trial |
To evaluate in patients initially randomized to receive baricitinib in the originating study, the effect of long-term administration of baricitinib on the progression of structural joint damage, joint space narrowing and bone erosion. score, duration of morning stiffness, and changes in the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) scores and in healthcare resource utilization.
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Valutare nei pazienti già randomizzati a ricevere baricitinib nello studio precedente, l'effetto della somministrazione a lungo termine di baricitinib sulla progressione del danno strutturale articolare, riduzione dello spazio articolare e di erosione ossea. Il punteggio relativo alla rigidità mattutina e cambiamenti nella qualità di vita misurato dal questionario EQ-5D-5L e l'utilizzo delle risorse sanitarie.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Have completed the final active treatment study visit in Study I4V-MC-JADV, I4V-MC-JADZ, I4V-MC-JADX, JADW, or I4V-MC-JADA.
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Pazienti che abbiano completato la fase di trattamento attivo nei precedenti studi I4V-MC-JADV, I4V-MC-JADZ, I4V-MC-JADX, JADW, o I4V-MC-JADA.
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria:
[2] have significant uncontrolled cerebro-cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, neuropsychiatric disorders, or abnormal laboratory values that developed during a previous baricitinib study that, in the opinion of the investigator, pose an unacceptable risk to the patient if investigational product continues to be administered
[3] have a known hypersensitivity to baricitinib or any component of this investigational product.
[4] had investigational product permanently discontinued at any time during a previous baricitinib study
[5] had temporary investigational product interruption at the final study visit of a previous baricitinib study and, in the opinion of the investigator, this poses an unacceptable risk for the patient’s participation in the study
[6] have any other condition that, in the opinion of the investigator, renders the patient unable to understand the nature, scope, and possible consequences of the study or precludes the patient from following and completing the protocol
[7] are females of childbearing potential who do not agree to use 2 forms of highly effective birth control when engaging in sexual intercourse while enrolled in the study and for at least 28 days following the last dose of investigational product
[8] are males who do not agree to use 2 forms of highly effective birth control while engaging in sexual intercourse with female partners of childbearing potential while enrolled in the study and for at least 28 days following the last dose of investigational product
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I pazienti saranno esclusi dallo studio se soddisfano uno dei seguenti criteri:
[2] eventi significativi e non controllati di natura cerebro-cardiovascolare, respiratoria, epatica, renale, gastrointestinale, endocrino, ematologica, disturbi neuropsichiatrici, o valori di laboratorio anormali che si sono sviluppati nel corso di uno studio baricitinib precedente che, secondo il parere dello sperimentatore, rappresentano un rischio inaccettabile per il paziente se il farmaco in studio continua ad essere somministrato
[3] ipersensibilità nota al baricitinib o qualsiasi componente di questo prodotto in studio.
[4] interruzione definitiva del farmaco in qualsiasi momento nel corso di un precedente studio baricitinib
[5] interruzione temporanea del farmaco in occasione della visita finale dello studio precedente e qualunque altra condizione che, secondo il parere dello sperimentatore, espone il paziente ad un rischio per la partecipazione allo studio
[6] altra condizione che, a giudizio dello sperimentatore, rende il paziente incapace di comprendere la natura, la portata e le possibili conseguenze dello studio o impedisce al paziente di seguire e completare il protocollo
[7] pazienti di sesso femminile in età fertile che non sono d'accordo nell'utilizzare 2 forme di controllo delle nascite altamente efficaci durante un rapporto sessuale, nel corso dellio studio e per almeno 28 giorni dopo l'ultima dose di prodotto in sperimentazione
[8] pazienti di sesso maschile che non sono d'accordo nell'utilizzare 2 forme di controllo delle nascite altamente efficaci durante un rapporto sessuale, nel corso dellio studio e per almeno 28 giorni dopo l'ultima dose di prodotto in sperimentazione |
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E.5 End points |
E.5.1 | Primary end point(s) |
a) Proportion of patients experiencing Treatment emergent adverse events (TEAEs), adverse events of special interest (AESIs), and serious adverse events (SAEs) over long term follow-up.
b) Temporary study drug interruptions and/or permanent study drug discontinuations over the long term follow-up
c) Vital signs and laboratory evaluations (including chemistry and hematology)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
a) All study visits.
b) All study visits except Visits 2, 5b, 19, ET, and 801.
c) All study visits. |
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E.5.2 | Secondary end point(s) |
a) Proportion of patients who maintain an improvement of 20, 50, or 70 percent, respectively, in the American College of Rheumatology criteria (ACR20, ACR50 and ACR70)
b) Proportion of patients who maintain a
• Disease Activity Score modified to include the 28 diathrodial joint count (DAS28)-high sensitivity C-reactive protein (hsCRP)/DAS28 erythrocyte sedimentation rate (ESR)≤3.2,
• Clinical Disease Activity Index (CDAI) ≤10, and
• Health Assessment Questionnaire Disability Index (HAQ-DI) improvement ≥0.22 and ≥0.3
c)Structural joint damage as measured by modified Total Sharp Score (mTSS) [van der Heijde method])
d) Proportion of patients with mTSS change ≤0
e) Joint space narrowing and bone erosion score
f) Duration of morning stiffness
g) European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) scores and healthcare resource utilization |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a)Change from baseline to Month 6 of the originating study through Months 12, 24, 36, 48, and 54 of baricitinib treatment
b)Same as a)
c)Change from baseline of originating study to Month 12 (Study JADX), Month 24 (JADX, JADV and JADZ), Month 36 (JADA, JADV, and JADZ) and Month 48 (JADA)
d)From baseline of originating study to Month 12 (Study JADX), Month 24 (JADX, JADV and JADZ), Month 36 (JADA, JADV, and JADZ) and Month 48 (JADA)
e)Change from baseline of originating study to Month 12 (Study JADX), Month 24 (JADX, JADV and JADZ ), Month 36 (JADA, JADV and JADZ) and Month 48 (JADA)
f)Change from baseline of originating study to 12, 24, 36, 48 and 54 months of baricitinib treatment
g)Change from baseline of originating study through Month 24 |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 127 |
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 | No |
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 |
Australia |
Belgium |
Brazil |
Canada |
China |
Croatia |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Latvia |
Lithuania |
Mexico |
Netherlands |
Poland |
Portugal |
Romania |
Russian Federation |
Slovakia |
Slovenia |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Turkey |
United Kingdom |
United States |
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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
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the date of the last visit or last scheduled procedure shown in the study schedule for the last active patient in the study
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ultima visita dell'ultimo paziente |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |