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 | 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 |
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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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O objectivo principal do estudo é a avaliaçao da segurança e tolerabilidade do baricitinib a longo prazo.
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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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Avaliar os doentes inicialmente aleatorizados no estudo de origem que receberam baricitinib, o efeito a longo prazo da administraçao de baricitinib na progressao dos danos estruturais nas articulaçoes, reduçao do espaço articular e erosao do osso, pontuaçao, duração da rigidez matinal das articulações e alteraçoes na escala Europeia de qualidade de Vida-5 Dimensoes-5 Nivel (EQ-5D-5L) pontuaçoes e utilizaçao de cuidados de saude |
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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, I4V-MC-JADA,I4V-MC-JADW or I4V-MC-JAGS.
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Doentes que completaram a visita final de tratamento activo nos estudos I4V-MC-JADV, I4V-MC-JADZ, I4V-MC-JADX, I4V-MC-JADA,I4V-MC-JADW ou I4V-MC-JAGS.
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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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•Tiver um problema de saúde grave, que na opinião do médico do estudo, constitua um risco aumentado para si.
•Se for uma mulher em idade fértil e não aceitar utilizar dois métodos contracetivos altamente eficazes durante a sua participação no estudo e pelo menos durante 28 dias após a última dose do medicamento experimental
•Se for um homem e não aceitar usar dois métodos contracetivos altamente eficazes durante as relações sexuais com parceiras que possam engravidar enquanto participa no estudo e pelo menos durante 28 dias após a última dose do medicamento experimental
•Desenvolveu uma reacção ao baricitinib mais conhecida como hipersensibilidade, que inclui reacções alérgicas.
•A medicação do estudo foi definitivamente descontinuada durante a sua participação no último estudo com Baricitinib.
•A medicação do estudo foi temporariamente descontinuada durante o período que incluía o fim do ultimo estudo com Baricitinib e o seu medico aconselhou que a sua participação neste estudo podia respresentar um risco acrescido para si.
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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, 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 1, 2, 5 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) ≤3.2 /
DAS28 erythrocyte sedimentation rate (ESR)≤3.2,
DAS28-hsCRP <2.6, and DAS28-
ESR <2.6
• Clinical Disease Activity Index (CDAI) ≤10, and CDAI ≤2.8;
• Simplified Disease Activity Index (SDAI) ≤11 and SDAI ≤3.3
• ACR/EULAR remission according
to the Boolean-based definition
• 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
h) Proportion of patients who maintain a CDAI score of ≤10 from
Studies JADV, JADW, and JADX after 3 months of treatment with
baricitinib 2 mg QD and with patients continuing treatment with the 4-
mg QD dose
I) Time to relapse (CDAI score >10 from Studies JADV, JADW, and JADX)
after randomization to the baricitinib 2-mg and 4-mg QD doses |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) Change from Month 6 (of the originating study) through each 12
of treatment
b) same as a)
c) Change from baseline of originating study through each 12 months of treatment
d) same as c)
e) same as c)
f) Change from baseline in duration of morning stiffness through each 12 months of treatment
g) Change from baseline through each 12 months of treatment
h) All study visits
I) All study visits |
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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 | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
Different dosage of the same product (2mg vs 4mg) |
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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 | 6 |
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 |
Australia |
Brazil |
Canada |
China |
India |
Israel |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
South Africa |
Taiwan |
Turkey |
United States |
Belgium |
Croatia |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
Italy |
Latvia |
Lithuania |
Netherlands |
Poland |
Portugal |
Romania |
Slovakia |
Slovenia |
Spain |
Sweden |
Switzerland |
United Kingdom |
Argentina |
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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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A data da ultima visita ou ultimo procedimento programado do estudo para o ultimo doente activo no estudo,
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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 | 10 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |