A Long-Term Extension Study of WA22762 to Evaluate Safety and Efficacy of Subcutaneous Tocilizumab in Participants With Moderate to Severe Rheumatoid Arthritis (RA).
5 de outubro de 2016 atualizado por: Hoffmann-La Roche
A Multicenter, Open-Label Long-Term Extension Study of WA22762 to Evaluate Safety and Efficacy of Subcutaneous Tocilizumab in Patients With Moderate to Severe Rheumatoid Arthritis
This multicenter, open-label, single arm, interventional, long-term extension (LTE) study will evaluate the safety and efficacy of tocilizumab (TCZ, RoActemra/Actemra) in French participants with moderate to severe RA who have completed the Week 97 visit of WA22762 LTE study (NCT01194414) (EudraCT Number 2010-018375-22).
Participants from France, who completed the Week 97 visit of the WA22762 LTE study and considered as responders (defined as having improvement in disease activity score based on 28-joint count [DAS28] of greater than [>] 1.2 points) will continue TCZ treatment within this local LTE study for a maximum of 156 weeks of subcutaneous (SC) TCZ treatment, or until SC TCZ becomes commercially available, whichever occurs first.
Visão geral do estudo
Tipo de estudo
Intervencional
Inscrição (Real)
11
Estágio
- Fase 3
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Bordeaux, França, 33076
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Montpellier, França, 34295
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Nantes, França, 44035
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Paris, França, 75679
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Strasbourg, França, 67098
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Toulouse, França, 31059
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Negative pregnancy test at screening and baseline
- Participants who have completed the 97-week WA22762 LTE study on SC or intravenous (IV) TCZ and who experienced, at any time during WA22762, clinically significant improvement in DAS28 (>1.2 points), and based on the investigator's judgment may continue to benefit from TCZ treatment in this study investigating the SC formulation
- No current or recent adverse events or laboratory findings preventing the use of the study drug dose of TCZ 162 mg SC at baseline visit
- Receiving treatment on an outpatient basis
- Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception during the study and for at least 3 months following the last dose of study drug
- Oral corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDS) up to the recommended dose are permitted if on stable dose regimen for greater than and equal to (>/=) 4 weeks prior to baseline
- Permitted non-biological disease-modifying anti-rheumatic drugs (DMARDs) are allowed
Exclusion Criteria:
- Participants who have prematurely withdrawn from the WA22762 LTE study for any reason
- Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies
- Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL) 1 agent, or a T-cell co stimulation modulator since the last administration of study drug in the WA22762 LTE study
- Immunization with a live/attenuated vaccine since the last administration of study drug in the WA22762 LTE study
- Diagnosis, since last WA22762 visit (Week 97), of rheumatic autoimmune disease other than rheumatoid arthritis; secondary Sjörgen's syndrome with RA is permitted
- Diagnosis, since last WA22762 visit (Week 97), of inflammatory joint disease other than RA
- Uncontrolled disease states, such as asthma or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids
- Evidence of serious uncontrolled concomitant disease
- Known active current or history of recurrent infection
- Primary or secondary immunodeficiency (history of or currently active)
- Body weight >150 kilograms (kg)
- Pregnant or lactating women
- Inadequate hematologic, renal or liver function
- History of alcohol, drug or chemical abuse within 1 year prior to screening
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Tocilizumab
Moderate to severe rheumatoid arthritis participants from France, who completed the Week 97 visit of the WA22762 LTE study and considered as responders (defined as having improvement in DAS28 of >1.2 points) will continue tocilizumab treatment within this local LTE study for a maximum of 156 weeks, or until SC TCZ becomes commercially available, whichever occurs first.
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Participants will receive TCZ 162 milligrams (mg) SC injection once a week.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Prazo: Baseline up to approximately 142 weeks
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An adverse event (AE) was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment.
An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment.
A SAE was any untoward medical occurrence that at any dose resulted in death, was life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity, and congenital anomaly/birth defect.
AEs included SAEs as well as non-serious AEs.
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Baseline up to approximately 142 weeks
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Percentage of Participants With AEs and SAEs Related to TCZ
Prazo: Baseline up to approximately 142 weeks
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An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
AEs included SAEs as well as non-serious AEs.
Causality of AEs based on physician's discretion: certain (AE after drug intake, not explained by other drugs, reaction on drug cessation [DC], relapse on re-intake of drug), probable/likely (AE after drug intake, not explained by other drugs, reaction on DC, no information on re-intake), possible (AE after drug intake, explained by other drugs, no information on DC), unlikely (not related to drug intake time, explained by other drugs).
AEs with causality of certain, probable/likely, and possible were considered TCZ related.
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Baseline up to approximately 142 weeks
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Percentage of Participants With Adverse Events of Special Interest (AESIs)
Prazo: Baseline up to approximately 142 weeks
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Adverse events of special interest (AESI) for this study included: infections (including opportunistic infections), myocardial infarction/acute coronary syndrome, gastrointestinal perforation and related events, malignancies, anaphylaxis / hypersensitivity reactions, demyelinating disorders, stroke, bleeding events and hepatic events.
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Baseline up to approximately 142 weeks
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Percentage of Participants With AESIs Related to TCZ
Prazo: Baseline up to approximately 142 weeks
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AESI for this study included: infections (including opportunistic infections), myocardial infarction/acute coronary syndrome, gastrointestinal perforation and related events, malignancies, anaphylaxis / hypersensitivity reactions, demyelinating disorders, stroke, bleeding events and hepatic events.
Percentage of participants with AESI related to the drug were presented.
Causality of AESIs based on physician's discretion: certain (AE after drug intake, not explained by other drugs, reaction on DC, relapse on re-intake of drug), probable/likely (AE after drug intake, not explained by other drugs, reaction on DC, no information on re-intake), possible (AE after drug intake, explained by other drugs, no information on DC), unlikely (not related to drug intake time, explained by other drugs).
AESIs with causality of certain, probable/likely, and possible were considered TCZ related.
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Baseline up to approximately 142 weeks
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Percentage of Participants With AEs Leading to TCZ Discontinuation, Interruption, or Dose Modification
Prazo: Baseline up to approximately 142 weeks
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An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug.
Percentage of participants with AE causing drug discontinuation, interruption and increase or decrease in dose of drug was presented.
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Baseline up to approximately 142 weeks
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Percentage of Participants With Clinically Significant Physical Examinations and Vital Signs Abnormalities
Prazo: Baseline up to approximately 142 weeks
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Criteria for potentially clinically important (PCI) change in vital signs: heart rate value of less than (<) 40 beats per minute and value greater than (>) 150 beats per minute, systolic blood pressure (SBP) of < 80 or >210 millimeter of mercury (mmHg), diastolic blood pressure (DBP) of <40 or >130 mmHg, body temperature <32 or > 40 degrees Celsius, respiratory rate of <10 or > 50 breaths/minute and criteria for PCI change in physical examination: >/=10% increase or decrease of body weight in kilograms (kg).
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Baseline up to approximately 142 weeks
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Percentage of Participants With Clinically Significant Laboratory Abnormalities
Prazo: Baseline up to approximately 142 weeks
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Criteria for laboratory tests clinically significant abnormalities included: hemoglobin, hematocrit and red blood cells (RBCs)(< 0.8*lower limit of normal[LLN]); leucocytes (<0.6/greater than [>]1.5*upper
limit of normal [ULN]); platelets (<0.5*LLN></0>1.75*ULN);
neutrophils, lymphocytes (<0.8*LLN></0>1.2*ULN);
eosinophils, basophils, monocytes (>1.2*ULN); total bilirubin, direct bilirubin, indirect bilirubin (>1.5*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (>3*ULN), total protein, albumin (<0.8*LLN></0>1.2*ULN);
creatinine, urea (>1.3*ULN); glucose (<0.6*LLN></0>1.5*ULN);
uric acid (>1.2*ULN); sodium, potassium, chloride, calcium, bicarbonate (<0.9*LLN></0>1.1*ULN);
urine RBCs, urine white blood cells (WBCs) (> or equal[=]20 high-powered field), urine bacteria >20 high-powered field.
Overall percentage of participants with any clinically significant laboratory abnormality was reported.
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Baseline up to approximately 142 weeks
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Percentage of Participants With Anti-TCZ Antibodies
Prazo: Baseline up to approximately 142 weeks
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Baseline up to approximately 142 weeks
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score
Prazo: Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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The DAS 28 ESR score is a measure of the participant's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment (PtGA) of disease activity (visual analog scale [VAS]: 0 millimeter [mm] = no disease activity to 100 mm=maximum disease activity) and the erythrocyte sedimentation rate (ESR in millimeters per hour [mm/hr]).
DAS28 was calculated using following formulas: DAS28-ESR = 0.56*square root (sqrt) (TJC28) + 0.28*sqrt (SJC28) + 0.70*natural logarithm (ln) (ESR) + 0.014*PtGA of disease activity.
A total possible score of 0 to approximately 10, with higher score indicating more severe disease activity.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in Simplified Disease Activity Index (SDAI) Score
Prazo: Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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The SDAI was calculated as (SJC [28 joints] + TJC [28 joints] + VAS ptGA + VAS physician global assessment of disease activity + C-reactive Protein (CRP) level in milligram/deciliter [mg/dL]).
VAS assessments: 0 centimeters (cm)=no disease activity to 10 cm=maximum disease activity.
SDAI score ranged from 0 to 86, with higher scores indicating increased disease activity.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in TJC
Prazo: Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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For TJC a total of 28 joints were assessed.
The presence of a tender joint was scored as 1 and absence as 0. Total score is calculated by adding the scores, which is ranging from 0 (best possible score or no tender joint) to 28 (worse possible score or all tender joints).
Lower scores indicate no tender joint and higher scores indicate worsening tender joints.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in SJC
Prazo: Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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For SJC, a total of 28 joints were assessed.
The presence of a swollen joint was scored as 1 and absence as 0. Total score is calculated by adding the scores, which is ranging from 0 (best possible score or no swollen joint) to 28 (worse possible score or all swollen joints).
Lower scores indicate no swollen joint and higher scores indicate worsening swollen joints.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Percentage of Participants With Clinical Remission
Prazo: Week 48, 108
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Clinical remission defined as:DAS28-ESR score < 2.6 and/or SDAI score </= 3.3.DAS28 score is measure of subject's disease activity calculated using TJC [28 joints],SJC [28 joints],PtGA of disease activity [ VAS:0mm= no disease activity to 100 mm=maximum disease activity] and ESR (mm/hr).
DAS28 was calculated as DAS28-ESR = 0.56*sqrt (TJC28) + 0.28*sqrt(SJC28) + 0.70* ln ESR + 0.014*PtGA of disease activity.
DAS28-ESR score ranged from 0 to approximately 10, higher score indicating more severe disease activity.
SDAI was calculated =[SJC (28 joints) + TJC (28 joints) + VAS PtGA + VAS physician global assessment of disease activity+CRP level(mg/dL)].
VAS assessments:0 mm=no disease activity to 100 mm=maximum disease activity.
SDAI score ranged from 0 to 86, with higher scores indicating increased disease activity.
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Week 48, 108
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Percentage of Participants With Concomitant Corticosteroid Discontinuation
Prazo: Baseline up to approximately 142 weeks
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Baseline up to approximately 142 weeks
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Percentage of Participants With Concomitant Corticosteroid Dose Reduction
Prazo: Baseline up to approximately 142 weeks
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Baseline up to approximately 142 weeks
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Time to Concomitant Corticosteroid Discontinuation
Prazo: Baseline up to approximately 142 weeks
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Time to corticosteroid discontinuation = (End date of corticosteroid treatment - date of first drug intake of this extension study) + 1.
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Baseline up to approximately 142 weeks
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Time to Concomitant Corticosteroid Dose Reduction
Prazo: Baseline up to approximately 142 weeks
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Time to corticosteroid dose reduction (days) = (Date of the first dose reduction of corticosteroid treatment - date of first drug intake of this extension study) + 1.
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Baseline up to approximately 142 weeks
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Change From Baseline in PtGA of Disease Activity
Prazo: Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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PtGA of disease activity over the previous 24 hours using a 100 mm VAS where left end of the line 0 mm =no disease activity and right end of the line 100 mm =maximum disease activity.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in Patient's Assessment of Pain
Prazo: Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Patient's assessment of pain over the previous 24 hours: using a VAS, left end of the line 0 mm=no pain to right end of the line 100 mm=unbearable pain.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score
Prazo: Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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The HAQ-DI questionnaire measures functional status (disability) and health-related quality of life.
It measures the participant's ability to perform everyday tasks.
The index consists of 20 questions regarding the function of the upper and lower extremities.
These questions are summarized in 8 categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common activities over past week.
Each question is evaluated according to the degree of severity on a 4-point scale.
Total score for HAQ-DI was the average of all questions and ranges from 0 = without any difficulty to 3 = unable to do.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in Physician's Global Assessment of Disease Activity
Prazo: Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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The Physician's Global Assessment of disease activity was assessed using a 0 to 100 mm horizontal VAS.
The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity".
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in ESR
Prazo: Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Blood samples were collected for ESR, which is an acute phase reactant and provides a non-specific measure of inflammation.
The test assesses the rate at which red blood cells fall in a test tube.
Normal range is 0-30 millimeters per hour (mm/hr).
A decrease in the level indicates reduction in inflammation and therefore improvement.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Change From Baseline in CRP
Prazo: Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Blood samples were collected for CRP, which is an acute phase reactant and a measure of inflammation.
Completer last visit: Last visit data for participants who completed the study.
Last visit: Last visit data for all participants (including those who discontinued prematurely).
Early withdrawal: Data at the time of early withdrawal for those participants who discontinued prematurely.
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Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de outubro de 2012
Conclusão Primária (Real)
1 de setembro de 2015
Conclusão do estudo (Real)
1 de setembro de 2015
Datas de inscrição no estudo
Enviado pela primeira vez
19 de novembro de 2012
Enviado pela primeira vez que atendeu aos critérios de CQ
27 de novembro de 2012
Primeira postagem (Estimativa)
28 de novembro de 2012
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
28 de novembro de 2016
Última atualização enviada que atendeu aos critérios de controle de qualidade
5 de outubro de 2016
Última verificação
1 de outubro de 2016
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- ML28544
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .
Ensaios clínicos em Tocilizumab
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Icahn School of Medicine at Mount SinaiRecrutamento
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Capital Medical UniversityRecrutamento
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Capital Medical UniversityAtivo, não recrutando
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Assistance Publique - Hôpitaux de ParisFresenius AGAinda não está recrutandoDoença de Deposição de Pirofosfato de CálcioFrança
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National Institute of Allergy and Infectious Diseases...RecrutamentoArterite de Células Gigantes (ACG)Estados Unidos
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Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityAinda não está recrutandoMastite Granulomatosa | Mastite Lobular Granulomatosa
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Janssen Research & Development, LLCAinda não está recrutando
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Regeneron PharmaceuticalsAinda não está recrutandoMieloma Múltiplo Recidivante/Refratário (MMRR)
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Shahid Beheshti University of Medical SciencesRecrutamentoRejeição de Transplante RenalIrã
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Assistance Publique - Hôpitaux de ParisConcluídoContágio do coronavírusFrança