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A Study of Tocilizumab and Methotrexate Treatment Strategies (Adding Tocilizumab to Methotrexate Versus Switching to Tocilizumab) in Patients With Active Rheumatoid Arthritis With Inadequate Response to Prior Methotrexate Treatment

16. července 2014 aktualizováno: Hoffmann-La Roche

Randomized Placebo-controlled Study of Two Treatment Strategies Based on Tocilizumab (TCZ) With or Without Methotrexate (MTX) and Possible Addition of Other Disease-modifying Anti-rheumatic Drugs (DMARDs) in Patients...

This 2 arm study will compare 2 treatment strategies based on tocilizumab in combination with methotrexate or placebo in patients with moderate to severe rheumatoid arthritis. Patients receiving methotrexate treatment will be randomized to receive either a) tocilizumab 8 mg intravenous (iv) every 4 weeks + methotrexate orally (po) weekly or b) tocilizumab 8 mg iv every 4 weeks + placebo po weekly. After the first 24 weeks of blinded treatment, treatment adjustments (increase or decrease of treatment intensity) may be introduced at intervals, based on response. The anticipated time on study treatment is up to 3 years, and the target sample size is approximately 470 patients.

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Typ studie

Intervenční

Zápis (Aktuální)

556

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

  • Brazílie
    • MG
      • Belo Horizonte, MG, Brazílie, 30130-100
    • RS
      • Porto Alegre, RS, Brazílie, 90035-903
    • SP
      • Sao Paulo, SP, Brazílie, 05403-000
      • Sao Paulo, SP, Brazílie, 04026-000
      • Sao Paulo, SP, Brazílie, 04039-004
  • Chorvatsko
      • Rijeka, Chorvatsko, 51000
      • Zagreb, Chorvatsko, 10000
  • Dánsko
      • Frederiksberg, Dánsko, 2000
      • Hellerup, Dánsko, 2900
      • Køge, Dánsko, 4600
  • Estonsko
      • Tallinn, Estonsko, 11312
      • Tallinn, Estonsko, 13419
  • Francie
      • Abbeville, Francie, 80142
      • Boulogne-billancourt, Francie, 92104
      • Brest, Francie, 29609
      • Echirolles, Francie, 38434
      • Le Kremlin Bicetre, Francie, 94275
      • Le Mans, Francie, 72037
      • Marseille, Francie, 13285
      • Marseille, Francie, 13385
      • Monaco, Francie, 98012
      • Nantes, Francie, 44035
      • Nice, Francie, 06202
      • Paris, Francie, 75571
      • Paris, Francie, 75679
      • Pierre Benite, Francie, 69495
      • Vandoeuvre-les-nancy, Francie, 54511
  • Holandsko
      • Amsterdam, Holandsko, 1105 AZ
      • Amsterdam, Holandsko, 1081 HV
      • Leiden, Holandsko, 2333 ZA
      • Maastricht, Holandsko, 6202 AZ
      • Nijmegen, Holandsko, 6525 GA
      • Utrecht, Holandsko, 3584 CX
  • Itálie
      • Ancona, Itálie, 60020
      • Bari, Itálie, 70124
      • Perugia, Itálie, 06122
      • Prato, Itálie, 59100
      • Roma, Itálie, 00168
  • Izrael
      • Afula, Izrael, 18101
      • Beer Sheva, Izrael, 8410101
      • Haifa, Izrael, 31048
      • Haifa, Izrael, 34362
      • Haifa, Izrael, 34354
      • Kfar Saba, Izrael, 44281
      • Ramat-Gan, Izrael, 52621
      • Rishon Lezion, Izrael
      • Tel Aviv, Izrael, 6423906
  • Lotyšsko
      • Bauska, Lotyšsko, 3901
      • Daugavpils, Lotyšsko, 5417
      • Liepaja, Lotyšsko, 3400
      • Riga, Lotyšsko, LV-1002
      • Riga, Lotyšsko, 1038
      • Riga, Lotyšsko, 1006
  • Norsko
      • Drammen, Norsko, 3004
      • Gjettum, Norsko, 1346
      • Kristiansand, Norsko, 4604
      • Lillehammer, Norsko, 2609
      • Moss, Norsko, 1535
      • Oslo, Norsko, 0319
  • Německo
      • Aachen, Německo, 52064
      • Berlin, Německo, 10117
      • Berlin, Německo, 13125
      • Dresden, Německo, 01307
      • Erlangen, Německo, 91054
      • Hamburg, Německo, 22081
      • Jena, Německo, 07747
      • Köln, Německo, 50924
      • Muenchen, Německo, 80336
      • Ratingen, Německo, 40882
      • Wuerzburg, Německo, 97080
  • Rumunsko
      • Bucharest, Rumunsko, 011172
      • Bucuresti, Rumunsko, 020983
  • Ruská Federace
      • Barnaul, Ruská Federace, 656024
      • Ekaterinburg, Ruská Federace, 620102
      • Irkutsk, Ruská Federace, 664047
      • Izhevsk, Ruská Federace, 426009
      • Kazan, Ruská Federace, 420012
      • Khanty-Mansiysk, Ruská Federace, 628011
      • Kursk, Ruská Federace, 305007
      • Moscow, Ruská Federace, 115522
      • Novosibirsk, Ruská Federace, 630117
      • Novosibirsk, Ruská Federace, 630099
      • St Petersburg, Ruská Federace, 191015
      • Tjumen, Ruská Federace, 625023
      • UFA, Ruská Federace, 450005
      • Ulyanovsk, Ruská Federace, 432063
      • Vladivostok, Ruská Federace, 690105
  • Spojené království
      • Cannock, Spojené království, WS11 5XY
      • Glasgow, Spojené království, G12 0YN
      • Leeds, Spojené království, LS7 4SA
      • London, Spojené království, SE5 9RS
      • Newcastle-upon-Tyne, Spojené království, NE2 4HH
      • Norwich, Spojené království, NR4 7UY
  • Spojené státy
    • California
      • Santa Monica, California, Spojené státy, 90404
      • Upland, California, Spojené státy, 91786
      • Whittier, California, Spojené státy, 90606
    • Florida
      • Aventura, Florida, Spojené státy, 33180
      • Naples, Florida, Spojené státy, 34102
      • Orange Park, Florida, Spojené státy, 32073
      • Plantation, Florida, Spojené státy, 33317
      • Sarasota, Florida, Spojené státy, 34239
      • South Miami, Florida, Spojené státy, 33143
      • Tamarac, Florida, Spojené státy, 33321
    • Minnesota
      • Eagan, Minnesota, Spojené státy, 55121
    • Nevada
      • Las Vegas, Nevada, Spojené státy, 89128
    • Ohio
      • Mayfield, Ohio, Spojené státy, 44143
      • Middleburg Heights, Ohio, Spojené státy, 44130
    • Oklahoma
      • Oklahoma City, Oklahoma, Spojené státy, 73104
    • Pennsylvania
      • West Reading, Pennsylvania, Spojené státy, 19611
    • South Carolina
      • Greenville, South Carolina, Spojené státy, 29601
    • Tennessee
      • Nashville, Tennessee, Spojené státy, 37205
    • Texas
      • Houston, Texas, Spojené státy, 77004
      • San Antonio, Texas, Spojené státy, 78217
    • Washington
      • Spokane, Washington, Spojené státy, 99204
  • Srbsko
      • Belgrade, Srbsko, 11000
      • Kragujevac, Srbsko, 34000
      • Niska Banja, Srbsko, 18250
      • Nova sad, Srbsko, 21000
  • Thajsko
      • Bangkok, Thajsko, 10300
      • Khon Kaen, Thajsko, 40002
      • Pathumthani, Thajsko, 12120
  • Řecko
      • Athens, Řecko, 11527
      • Thessaloniki, Řecko, 54642
      • Thessaloniki, Řecko, 54636
  • Španělsko
      • Barcelona, Španělsko, 08003
      • Madrid, Španělsko, 28046
      • Madrid, Španělsko, 28041
      • Madrid, Španělsko, 28007
      • Madrid, Španělsko, 28222
      • Sevilla, Španělsko, 41009
    • Asturias
      • Oviedo, Asturias, Španělsko, 33006
    • La Coruña
      • La Coruna, La Coruña, Španělsko, 15006
      • Santiago De Compostela, La Coruña, Španělsko, 15706
    • Madrid
      • Leganes, Madrid, Španělsko, 28191
    • Vizcaya
      • Bilbao, Vizcaya, Španělsko, 48013
  • Švédsko
      • Goeteborg, Švédsko, 41345
      • Umea, Švédsko, 90185

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

18 let a starší (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

Inclusion Criteria:

  • adult patients, ≥ 18 years of age;
  • moderate to severe active rheumatoid arthritis (Disease Activity Score (DAS28) > 4.4);
  • inadequate response to methotrexate;
  • on a stable dose of ≥ 15mg/week methotrexate for at least 6 weeks.

Exclusion Criteria:

  • prior treatment with a biologic;
  • Rheumatoid arthritis (RA) functional class IV;
  • known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections;
  • evidence of active malignant disease.

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: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Čtyřnásobek

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: Tocilizumab + Methotrexate
Tocilizumab 8 mg/kg (up to 800 mg) intravenous (IV) once every 4 weeks + weekly oral methotrexate continuing at the patient's pre-study dose for 24 weeks. Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day). Week 24 to Week 52 the dose of tocilizumab and methotrexate remained the same. Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drugs (DMARDS) added. Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment. After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded methotrexate if a flare occurred.
Lék: tocilizumab [RoActemra/Actemra]
tocilizumab 8 mg IV every 4 weeks.
Ostatní jména:
  • RoActemra/Actemra
Lék: methotrexate
Approximately 15-17 mg methotrexate capsule orally once a week.
Komparátor placeba: Tocilizumab + Placebo
Tocilizumab 8 mg/kg (up to 800 mg) IV once every 4 weeks + weekly oral placebo to methotrexate continuing at the patient's pre-study dose for 24 weeks. Patients taking oral corticosteroids remained on their pre-study dose (up to 10 mg/day). Week 24 to Week 52 the dose of tocilizumab and placebo to methotrexate remained the same. Based on DAS28 assessments, corticosteroid dose was adjusted and disease-modifying antirheumatic drug (DMARDS) added. Week 52 to Week 104, based on the DAS28 assessment, treatment was adjusted to one of four protocol specified treatment regimens: Treatment tapering, Continued treatment, Treatment intensification or Maintenance treatment. After Week 100, patients who discontinued tocilizumab because of remission were retreated with the last effective dose of tocilizumab or blinded placebo to methotrexate if a flare occurred.
Lék: tocilizumab [RoActemra/Actemra]
tocilizumab 8 mg IV every 4 weeks.
Ostatní jména:
  • RoActemra/Actemra
Lék: placebo
Placebo matching methotrexate capsule taken orally once a week.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Percentage of Participants With Disease Activity Score 28 Joints (DAS28) Remission at Week 24
Časové okno: Week 24
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.
Week 24

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Percentage of Participants With American College of Rheumatology (ACR20) Response
Časové okno: Baseline, Weeks 24, 52, 104
ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
Baseline, Weeks 24, 52, 104
Percentage of Participants With ACR50 Response
Časové okno: Baseline, Weeks 24, 52, 104
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
Baseline, Weeks 24, 52, 104
Percentage of Participants With ACR70 Response
Časové okno: Baseline, Weeks 24, 52, 104
ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
Baseline, Weeks 24, 52, 104
Percentage of Participants With ACR90 Response
Časové okno: Baseline, Weeks 24, 52, 104
ACR90 response is defined as a ≥ 90% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
Baseline, Weeks 24, 52, 104
Time to First ACR20 Response
Časové okno: 104 Weeks
Time in days from first administration of study drug until ACR20 response. ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
104 Weeks
Time to First ACR50 Response
Časové okno: 104 Weeks
Time in days from first administration of study drug until ACR50 response. ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate).
104 Weeks
Time to First ACR70 Response
Časové okno: 104 Weeks
Time in days from first administration of study drug until ACR70 response. ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
104 Weeks
Time to First ACR90 Response
Časové okno: 104 Weeks
Time in days from first administration of study drug until ACR90 response. ACR90 response is defined as a ≥ 90% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
104 Weeks
Area Under Curve (AUC) DAS28
Časové okno: Baseline to Week 24
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. AUC DAS28 was averaged over study days. Analysis of Covariance was adjusted for Baseline DAS28 as a covariate and treatment group and region as fixed factors. Higher calculated AUC values are worse (indicate higher disease activity).
Baseline to Week 24
Percentage of Participants With Disease Activity Score 28 (DAS28) Remission
Časové okno: Week 52
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.
Week 52
Percentage of Participants With DAS28 Low Disease Activity (LDAS)
Časové okno: Weeks 24, 52
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDAS is defined as DAS28 ≤ 3.2.
Weeks 24, 52
Change From Baseline in DAS28 Score
Časové okno: Baseline, Weeks 24, 52
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A higher value indicated higher disease activity. A negative change from Baseline indicated improvement.
Baseline, Weeks 24, 52
Percentage of Participants With Good or Moderate European League (EULAR) DAS28 Responses
Časové okno: Baseline, 24, 52

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.

European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 or a change from Baseline < -1.2.

EULAR Moderate response: DAS28 > 3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.
Baseline, 24, 52
Change From Baseline in Swollen Joint Count
Časové okno: Baseline, Weeks 24, 52
66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement.
Baseline, Weeks 24, 52
Change From Baseline in Tender Joint Count
Časové okno: Baseline, Weeks 24, 52
68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement.
Baseline, Weeks 24, 52
Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (VAS)
Časové okno: Baseline, Weeks 24, 52
The patients global assessment of disease activity was assessed on a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and was 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 change from Baseline indicated improvement.
Baseline, Weeks 24, 52
Change From Baseline in Physician Global Assessment of Disease Activity Visual Analog Scale (VAS)
Časové okno: Baseline, Weeks 24, 52
The physician global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (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). A negative change from Baseline indicated improvement.
Baseline, Weeks 24, 52
Change From Baseline in Patient Global Assessment of Pain (VAS)
Časové okno: Baseline, Weeks 24, 52
The patient assessed their pain using a 0 to 100 millimeter (mm) horizontal visual analogue scale (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 as "unbearable pain". A negative change from Baseline indicated improvement.
Baseline, Weeks 24, 52
Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
Časové okno: Baseline, Weeks 24, 52
Blood was collected for Erythrocyte Sedimentation Rate (ESR) (a test that assesses tissue inflammation) and was analyzed at a local laboratory. ESR was measured in millimeters/hour (mm/hr). A reduction in the level is considered an improvement.
Baseline, Weeks 24, 52
Change From Baseline in C-Reactive Protein (CRP)
Časové okno: Baseline, Weeks 24, 52
Blood was collected for C-Reactive Protein (CRP) (a test for analysis of inflammatory and infectious disorders) and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.
Baseline, Weeks 24, 52
Change From Baseline in the Health Assessment Questionnaire Disability Index
Časové okno: Baseline, Weeks 24, 52
The Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis, consisting of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. There are 4 possible responses for each question: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty and 3=unable to do. The score for each of the domains is the highest (worst) score in each domain. A patient must have a domain score for at least 6 of 8 domains to calculate a valid HAQ-DI score which is the sum of domain scores, divided by the number of domains that have a score for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.
Baseline, Weeks 24, 52
Change From Baseline in Total Genant Modified Sharp Scores (GSS)
Časové okno: Baseline, Weeks 24, 52, 104
Radiographs were taken of each hand and foot at Baseline, Weeks 24, 52 and104 and were evaluated using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 98 and in the feet 42. The maximum scores for joint space narrowing (JSN) in the hands was104 and in the feet 48. The total score was the sum of scores for erosions and JSN. The maximum total modified GSS was 292. A lower number change from Baseline was better. Analysis of covariance model, with Baseline DAS28 as a covariate and treatment and site as fixed factors.
Baseline, Weeks 24, 52, 104
Change From Baseline in Joint Space Narrowing Score
Časové okno: Baseline, Weeks 24, 52, 104
A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum scores for joint space narrowing (JSN) in the hands was 104 and in the feet 48 for a total possible score of 0 to 152. A lower change from Baseline indicated a better score. Analysis of covariance model included baseline x-ray and DAS28 as covariates and treatment group and region as fixed effects.
Baseline, Weeks 24, 52, 104
Change From Baseline in Erosion Score
Časové okno: Baseline, Weeks 24, 52, 104
A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. The maximum erosion score in the hands was 98 and in the feet 42 for a total possible score of 0 to 140. A lower number change from Baseline indicated a better score.
Baseline, Weeks 24, 52, 104
Percentage of Participants Discontinuing Tocilizumab Due to Remission
Časové okno: Weeks 52, 104
The percentage of participants who stopped treatment with tocilizumab due to remission.
Weeks 52, 104
Percentage of Participants Who Withdrew Due to Lack of Sufficient Therapeutic Response
Časové okno: Up to 3 years
Lack of Sufficient Therapeutic Response was defined as the patient not responding to the drug as expected.
Up to 3 years
Percentage of Participants Who Withdrew Due to Safety Reasons
Časové okno: Up to 3 years
Safety reasons were defined as adverse events, intercurrent illness or death. An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.
Up to 3 years
Change From Baseline in Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL)
Časové okno: Baseline, Weeks 24, 52, 104
The RAQoL is a disease specific patient-reported outcome measure that determines the effect rheumatoid arthritis has on a patient's quality of life consisting of 30 questions that are answered either yes=1 or no=0 for a total possible score ranging from 0 (best) to 30 (worst). A negative change from Baseline indicated improvement.
Baseline, Weeks 24, 52, 104
Change From Baseline in Academic Medical Center (AMC) Linear Disability Scale (ALDS)
Časové okno: Baseline, Weeks 104
The Academic Medical Center (AMC) Linear Disability Score (ALDS) evaluates the participant's ability to perform activities of daily life consisting of 77 questions answered yes or no . The question difficulty and the patient's ability are arranged on a single hierarchical linear scale. ALDS scores range from 10 to 90 with a higher score representing higher functional status. A positive change from Baseline indicated improvement.
Baseline, Weeks 104
Area Under the Curve (AUC) From Baseline to Week 24 for ACR Response
Časové okno: Baseline to Week 24
ACR response was defined as an improvement (reduction) compared with baseline for both total joint count-68 joints and swollen joint count-66 joints, and for three of five variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) where 0=no pain to 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where: 0=no disease activity to 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate]. Area under the curve for ACR response to Week 24 was averaged over study days. Analysis of covariance model includes treatment group, region and baseline DAS28 (≤ 5.5 and > 5.5) as fixed factors.
Baseline to Week 24
Area Under the Curve (AUC) From Baseline to Week 52 for ACR Response
Časové okno: Baseline to Week 52
ACR response was defined as an improvement (reduction) compared with baseline for both total joint count-68 joints and swollen joint count-66 joints, and for three of five variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) where 0=no pain to 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where: 0=no disease activity to 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].Area under the curve for ACR response to Week 52 averaged over study days. Analysis of covariance model includes treatment group, region and baseline DAS28 (<=5.5 and >5.5) as fixed factors.
Baseline to Week 52
Time to Tocilizumab Remission
Časové okno: 104 Weeks
The time in days from initial study drug treatment to tocilizumab remission that occurred when the patient discontinued treatment with tocilizumab.
104 Weeks
Time to Drug-Free Remission
Časové okno: 104 Weeks
The time in days from initial study drug treatment to drug free remission that occurred when the participant was able to discontinue tocilizumab, methotrexate/placebo and open label disease-modifying antirheumatic drugs (DMARDS).
104 Weeks
Time to Flare After Tocilizumab Remission
Časové okno: 104 Weeks
The time in days to a flare (recurrence of disease symptoms) after the patient discontinued treatment with tocilizumab.
104 Weeks
Time to Restart of Treatment After Discontinuation/Remission
Časové okno: 104 Weeks
The time in days from treatment discontinuation or remission to the restart of treatment.
104 Weeks

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Hoffmann-La Roche

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

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

1. března 2009

Primární dokončení (Aktuální)

1. srpna 2010

Dokončení studie (Aktuální)

1. ledna 2013

Termíny zápisu do studia

První předloženo

16. prosince 2008

První předloženo, které splnilo kritéria kontroly kvality

16. prosince 2008

První zveřejněno (Odhad)

17. prosince 2008

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Odhad)

18. července 2014

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

16. července 2014

Naposledy ověřeno

1. července 2014

Více informací

Termíny související s touto studií

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • MA21488
  • 2008-001847-20

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

Klinické studie na tocilizumab [RoActemra/Actemra]

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Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

CROs by country

CROs in Mongolia

Podmínky

Vzácné nemoci

Drogové intervence

Doplňky stravy

Sponzor / Spolupracovníci

Místa

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