A Long Term Extension Study of WA19926 (NCT01007435) of Tocilizumab (RoActemra/Actemra) in Participants With Early, Moderate to Severe Rheumatoid Arthritis (RA)
11. února 2019 aktualizováno: Hoffmann-La Roche
A Multicenter, Open-Label, Single Arm, Long Term Extension Study of WA19926 to Describe Safety During Treatment With Tocilizumab in Patients With Early, Moderate to Severe Rheumatoid Arthritis
This open-label, single arm, multicenter long-term extension study of WA19926 (NCT01007435) will evaluate the safety and efficacy of tocilizumab in participants with early, moderate to severe RA who have completed the 104-week WA19926 (NCT01007435) core study.
Eligible participants will be those who are expected to benefit from the study medicine based on the investigator's discretion.
Přehled studie
Typ studie
Intervenční
Zápis (Aktuální)
23
Fáze
- Fáze 3
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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GO
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Goiania, GO, Brazílie, 74110-120
- CIP - Centro Internacional de Pesquisa
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MG
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Juiz de Fora, MG, Brazílie, 36036-330
- Centro Mineiro de Pesquisa - CMiP
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PR
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Curtiba, PR, Brazílie, 80030-110
- Centro de Estudos em Terapias Inovadoras - CETI
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RS
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Porto Alegre, RS, Brazílie, 90610-000
- Hospital Sao Lucas - PUCRS
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SP
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Sao Paulo, SP, Brazílie, 04026-000
- Universidade Federal de Sao Paulo - UNIFESP; Reumatologia
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Sao Paulo, SP, Brazílie, 04266-010
- Centro Paulista de Investigacao Clinica - CEPIC
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
1 rok a starší (Dítě, Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
Inclusion Criteria:
- Participants who completed their last WA19926 (NCT01649804) core study visit (Week 104) and who may benefit from study drug treatment according to the Investigator's assessment
- No current or recent adverse event or laboratory finding preventing the use of tocilizumab 8 mg/kg at baseline visit
- Women of childbearing potential must agree to use highly reliable contraception during the treatment period
Exclusion Criteria:
- Pregnant or breastfeeding females
- Participants who have withdrawn prematurely from the WA19926 (NCT01649804) core study for any reason
- Treatment with any investigational agent or cell-depleting therapies since the last administration of study drug in WA19926 (NCT01649804)
- Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL) 1 agent, or a T-cell costimulation modulator since the last administration of study drug in WA19926 (NCT01649804)
- Immunization with a live/attenuated vaccine since the last administration of study drug in WA19926 (NCT01649804)
- Diagnosis since last WA19926 (NCT01649804) visit (Week 104) of rheumatic autoimmune disease other than RA
- Diagnosis since last WA19926 (NCT01649804) visit (Week 104) of inflammatory joint disease other than RA
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, including tocilizumab and its excipients
- Evidence of severe uncontrolled concomitant disease or disorder
- Known active infections or history of recurrent infections
- Active tuberculosis requiring treatment in the previous 3 years
- History of alcohol, drug or chemical abuse since inclusion in the WA19926 (NCT01649804) study
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: Tocilizumab
Participants will receive tocilizumab 8 milligrams per kilogram (mg/kg) intravenously (IV) every 4 weeks for up to 104 weeks.
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Participants will receive tocilizumab 8 mg/kg IV every 4 weeks for up to 104 weeks.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Časové okno: Baseline up to approximately 104 weeks
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An adverse event (AE) is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom or disease temporarily associated with use of study drug, regardless of its relation to study drug.
A TEAE is an AE that occurs only once treatment has started.
An SAE can be a) fatal, b) life-threatening, c) requires/prolongs hospitalization, d) results in persistent/significant incapacity/disability, e) results in congenital anomaly/birth defect or f) is considered as a significant medical event by the investigator.
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Baseline up to approximately 104 weeks
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Percentage of Participants With TEAEs of Special Interest
Časové okno: Baseline up to approximately 104 weeks
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An AE is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom or disease temporarily associated with use of study drug, regardless of its relation to study drug.
A TEAE is an AE that occurs only once treatment has started.
Nine categories of AE of special interest are identified for tocilizumab which includes a) serious/medically significant infections, b) myocardial infarction/acute coronary syndrome, c) gastrointestinal perforations, d) malignancies, e) anaphylaxis/hypersensitivity reactions, f) demyelinating disorders, g) stroke, h) serious and/or medically significant bleeding events, and i) serious/medically significant hepatic events.
Data reported is an average of the nine categories.
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Baseline up to approximately 104 weeks
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Percentage of Participants With TEAEs Leading to Change in Dose or Study Drug Discontinuation
Časové okno: Baseline up to approximately 104 weeks
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An AE is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom or disease temporarily associated with use of study drug, regardless of its relation to study drug.
A TEAE is an AE that occurs only once treatment has started.
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Baseline up to approximately 104 weeks
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Change From Baseline (CFB) in Disease Activity Score 28 Using Erythrocyte Sedimentation Rate (DAS28-ESR) at Specified Time Points
Časové okno: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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The DAS28-ESR is a combined index for measuring disease activity in rheumatoid arthritis (RA).
The index includes swollen joint counts (SJC) and tender joint counts (TJC), both scored 0-28 (higher scores indicate higher disease activity), as well as acute phase response (APR) determined as erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and general health (GH) (patient global assessment of disease activity [PGA] using visual analog scale [VAS], range 1-100 millimeters [mm]) (higher scores indicate higher disease activity).
DAS28-ESR is calculated according to the following formula: DAS28-ESR equals (=) [0.56 multiplied by (*) the square root (√) of TJC] plus (+) [0.28 * √ of SJC] + (0.70 * the natural logarithm [ln] ESR in mm/h) + (0.014*GH in mm VAS).
DAS28-ESR scale is transformed and ranges from 0 to 10.
A negative CFB indicated improvement.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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CFB in Simplified Disease Activity Index (SDAI) Score at Specified Time Points
Časové okno: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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The SDAI is a combined index for measuring disease activity.
SDAI is the sum of TJC and SJC, both scored 0-28 (higher scores indicate higher disease activity), physician global assessment (PhGA) and PGA of disease activity, both scored 0 to 10 centimeters (cm) as assessed by VAS, and C-reactive protein level (CRP) in milligrams per deciliter (mg/dL) where normal is less than (<) 1 mg/dL.
SDAI is calculated according to the following formula: SDAI = TJC + SJC + PhGA + PGA + CRP.
SDAI ranges from 0 to 86.
A negative CFB indicated improvement.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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CFB in Swollen Joint Count (SJC) at Specified Time Points
Časové okno: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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For SJC, a total of 66 joints are assessed.
The presence of a swollen joint is scored as 1 and absence as 0. Total score is calculated by adding the scores, which ranges from 0 (best possible score or no swollen joint) to 66 (worse possible score or all swollen joints).
Lower scores indicated no swollen joint and higher scores indicated worsening swollen joints.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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CFB in Tender Joint Count (TJC) at Specified Time Points
Časové okno: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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The number of tender joints is recorded on the joint assessment form, no tenderness = 0, tenderness = 1, for 68 joints and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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Percentage of Participants Reaching Clinical Remission (DAS28-ESR Score Less Than [<] 2.6 and/or SDAI Score Less Than or Equal to [</=] 3.3) Among Participants for Whom Tocilizumab Treatment Was Discontinued
Časové okno: Baseline up to approximately 104 weeks
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Remission: DAS28-ESR score <2.6 and SDAI score </=3.3.
DAS28-ESR index included SJC and TJC, both scored 0-28, as well as APR determined as ESR in mm/hr, and GH (ranges 1-100 mm; higher scores=higher disease activity).
DAS28=(0.56*√TJC)+(0.28*√SJC)
+(0.70*ln
ESR) +(0.014*GH).
DAS28-ESR scale is transformed and ranges from 0 to 10. Negative CFB indicated improvement.
DAS28 >2.6 (clinical remission); DAS28 2.6 to 3.2 (low disease activity); DAS28 >3.2 to 5.1 = moderate to high disease activity.
SDAI is sum of TJC and SJC (both scored 0-28), PhGA and PGA of disease activity (both scored 0 to 10 cm as assessed by VAS, higher scores=higher disease activity), and CRP in mg/dL where normal is <1 mg/dL.
SDAI=TJC + SJC + PhGA + PGA + CRP.
SDAI ranged from 0 to 86.
A negative CFB indicated improvement.
SDAI <=3.3 (clinical remission), >3.4 to 11 (low disease activity) >11 to 26 (moderate disease activity), and >26 = (high/severe disease activity).
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Baseline up to approximately 104 weeks
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Time to RA Crisis Among Participants Who Discontinued After Clinical Remission
Časové okno: Baseline up to approximately 104 weeks
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RA crisis is any worsening of participant disease acitivity that, in the opinion of the investigator, required intensified treatment other than supportive therapy, and may have included restart of the treatment with the study drug.
Time to RA crisis is defined as the period of remission without drug until the RA crisis documentation.
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Baseline up to approximately 104 weeks
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CFB in PGA of Disease Activity Using VAS Score at Specified Time Points
Časové okno: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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PGA of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant.
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" (maximum arthritis disease activity).
A negative CFB indicated improvement.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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CFB in PGA of Pain Using VAS Score at Specified Time Points
Časové okno: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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PGA of pain is assessed on a 0 to 100 mm horizontal VAS.
The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm, and is described as "unbearable pain".
A negative change indicated improvement.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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CFB in PhGA of Disease Activity Using VAS Score at Specified Time Points
Časové okno: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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PhGA of disease activity is assessed on a 0 to 100 mm horizontal VAS by the physician.
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" (maximum arthritis disease activity).
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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CFB in Health Assessment Questionnaire-Disease Index (HAQ-DI) Score at Specified Time Points
Časové okno: Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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HAQ-DI is a self-reported participant questionnaire specific for RA.
It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities.
Each domain has at least 2 component questions.
There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do.
Total score for HAQ-DI is the sum of all questions and ranges from 0 = without any difficulty to 60 = unable to do.
A negative CFB indicates improvement.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
9. prosince 2013
Primární dokončení (Aktuální)
11. května 2016
Dokončení studie (Aktuální)
11. května 2016
Termíny zápisu do studia
První předloženo
16. srpna 2012
První předloženo, které splnilo kritéria kontroly kvality
16. srpna 2012
První zveřejněno (Odhad)
20. srpna 2012
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
13. května 2019
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
11. února 2019
Naposledy ověřeno
1. února 2019
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
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- ML28080
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Studuje produkt zařízení regulovaný americkým úřadem FDA
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