An Extension to Study MA21573, Evaluating Tocilizumab in Patients With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biological DMARDs and/or Anti-tumor Necrosis Factor (TNF) Therapy

An Extension Phase of the Multi-National Open-Label Study (MA21573) to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab in Patients With Active Rheumatoid Arthritis on Background Non-biologic DMARDs Who Have an Inadequate Response to Current Non-biologic DMARD and/or Anti-TNF Therapy.

This study was an extension to study MA21573 [NCT00750880], which was an open label single arm study to investigate the safety, tolerability and efficacy of tocilizumab monotherapy, or combination therapy with non-biological disease-modifying antirheumatic drugs (DMARDS), in patients with moderate to severe active rheumatoid arthritis. Patients who completed the 24 week core study, and had at least a moderate European League Against Rheumatism (EULAR) response, were eligible to enter this long-term extension study, and received tocilizumab 8 mg/kg intravenous (iv) every 4 weeks. The anticipated time on study treatment was 1-2 years, and the target sample size was > 500 individuals.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: tocilizumab [RoActemra/Actemra]

• Study Type: Interventional
• Enrollment (Actual): 934
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia, 2601
  • New South Wales
    • Coffs Harbour, New South Wales, Australia, 2450
    • Kogarah, New South Wales, Australia, 2217
  • Queensland
    • Cairns, Queensland, Australia, 4870
  • South Australia
    • Adelaide, South Australia, Australia, 5041
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
    • Geelong, Victoria, Australia, 3220
    • Melbourne, Victoria, Australia, 3168
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5M 0H4
    • Lethbridge, Alberta, Canada, T1J 0N9
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 3G8
    • Nanaimo, British Columbia, Canada, V9S 4S1
    • Vancouver, British Columbia, Canada, V5Z 3Y1
    • Vancouver, British Columbia, Canada, V5Z 1L7
  • New Brunswick
    • Quispamsis, New Brunswick, Canada, E2E 4J8
  • Newfoundland and Labrador
    • St John's, Newfoundland and Labrador, Canada, A1C 5B8
  • Ontario
    • Hamilton, Ontario, Canada, L8N 1Y2
    • Ottawa, Ontario, Canada, K1H 8L6
    • Toronto, Ontario, Canada, M4K 1N2
    • Toronto, Ontario, Canada, M5T 2S8
    • Toronto, Ontario, Canada, M5G 1X5
    • Windsor, Ontario, Canada, N8X 5A6
  • Quebec
    • Laval, Quebec, Canada, H7G 2E6
    • Montreal, Quebec, Canada, H2L 1S6
    • Montreal, Quebec, Canada, H2L 4M1
    • Quebec City, Quebec, Canada, G1V 3M7
    • Rimouski, Quebec, Canada, G5L 8W1
    • Sherbrooke, Quebec, Canada, J1H 5N4
    • St-eustache, Quebec, Canada, J7P 4J2
    • Trois-rivieres, Quebec, Canada, G8Z 1Y2
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 0H6
• Czech Republic
  • Bruntal, Czech Republic, 792 01
  • Ostrava, Czech Republic, 722 00
  • Praha, Czech Republic, 128 50
  • Sokolov, Czech Republic, 356 01
  • Uherske Hradiste, Czech Republic, 686 01
  • Zlin, Czech Republic, 760 01
• France
  • Belfort, France, 90016
  • Caen, France, 14033
  • Cahors, France, 46005
  • Corbeil-essonnes, France, 91106
  • Dijon, France, 21000
  • La Rochelle, France, 17019
  • Lievin, France, 62806
  • Lomme, France, 59462
  • Lyon, France, 69437
  • Lyon, France, 69365
  • Marseille, France, 13385
  • Montivilliers, France, 76290
  • Montpellier, France, 34295
  • Mulhouse, France, 68070
  • Paris, France, 75674
  • Poitiers, France, 86021
  • Reims, France, 51092
  • Roubaix, France, 59056
  • St Brieuc, France, 22027
  • Strasbourg, France, 67098
  • Toulouse, France, 31059
  • Valence, France, 26000
  • Valenciennes, France, 59322
• Greece
  • Heraklion, Greece, 711 10
• Hungary
  • Budapest, Hungary, 1023
  • Eger, Hungary, 3300
  • Szeged, Hungary, 6724
  • Veszprem, Hungary, 8200
• Italy
  • Arenzano, Italy, 16011
  • Legnano, Italy, 20025
  • Milano, Italy, 20122
  • Milano, Italy, 20162
  • Milano, Italy, 20132
  • Modena, Italy, 41100
  • Monserrato, Italy, 09042
  • Novara, Italy, 28100
  • Palermo, Italy, 90127
  • Potenza, Italy, 85100
  • Roma, Italy, 00144
  • Roma, Italy, 00152
  • Siena, Italy, 53100
  • Varese, Italy, 21100
• Netherlands
  • 'S Hertogenbosch, Netherlands, 5223 GZ
  • Alkmaar, Netherlands, 1815 JD
  • Amsterdam, Netherlands, 1056 AB
  • Apeldoorn, Netherlands, 7300 DS
  • Arnhem, Netherlands, 6815 AD
  • Bergen Op Zoom, Netherlands, 4624 VT
  • Den Haag, Netherlands, 2545 CH
  • Den Haag, Netherlands, 2597 AX
  • Den Helder, Netherlands, 1782GZ
  • Enschede, Netherlands, 7511 JX
  • Gouda, Netherlands, 2803 HH
  • Heerlen, Netherlands, 6419 PC
  • Hilversum, Netherlands, 1213 HX
  • Leeuwarden, Netherlands, 8934 AD
  • Nieuwegein, Netherlands, 3430 EM
  • Nijmegen, Netherlands, 6522 JV
  • Roosendaal, Netherlands, 4708 AE
  • Rotterdam, Netherlands, 3079 DZ
  • Rotterdam, Netherlands, 3015 CE
  • Schiedam, Netherlands, 3116 BA
  • Spijkenisse, Netherlands, 3201 GZ
  • Vlissingen, Netherlands, 4382 EE
• Poland
  • Krakow, Poland, 31-121
  • Poznan, Poland, 61-545
  • Wroclaw, Poland, 50-556
• Portugal
  • Almada, Portugal, 2801-951
  • Coimbra, Portugal, 3000-075
  • Lisboa, Portugal, 1649-035
  • Lisboa, Portugal, 1349-019
  • Porto, Portugal, 4200-319
• Romania
  • Bucharest, Romania, 020475
  • Bucharest, Romania, 011172
  • Cluj-napoca, Romania, 400006
• Saudi Arabia
  • Jeddah, Saudi Arabia, 21499
  • Jeddah, Saudi Arabia, 21423
  • Jeddah, Saudi Arabia, 21461
• Spain
  • Alicante, Spain, 03010
  • Almeria, Spain, 04009
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08035
  • Barcelona, Spain, 08907
  • Barcelona, Spain, 08025
  • Caceres, Spain, 10310
  • Cordoba, Spain, 14004
  • Granada, Spain, 18014
  • Huesca, Spain, 22004
  • Lugo, Spain, 27004
  • Madrid, Spain, 28006
  • Madrid, Spain, 28905
  • Malaga, Spain, 29010
  • Salamanca, Spain, 37007
  • Sevilla, Spain, 41013
  • Valencia, Spain, 46017
  • Valencia, Spain, 46010
  • Alicante
    • Elche, Alicante, Spain, 03203
    • Elda, Alicante, Spain, 03600
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
    • Terrassa, Barcelona, Spain, 08221
  • La Coruña
    • La Coruna, La Coruña, Spain, 15006
  • Las Palmas
    • Las Palmas De Gran Canaria, Las Palmas, Spain, 35020
  • Tenerife
    • La Laguna, Tenerife, Spain, 38320
• United Kingdom
  • Barnsley, United Kingdom, S75 2EP
  • Basingstoke, United Kingdom, RG24 9NA
  • Bournemouth, United Kingdom, BH23 2JX
  • Brighton, United Kingdom, BN2 5BE
  • Burton on Trent, United Kingdom, DE13 0RB
  • Bury St Edmonds, United Kingdom, IP33 2QZ
  • Cambridge, United Kingdom, CB2 2QQ
  • Cardiff, United Kingdom, CF14 4XW
  • Chelmsford, United Kingdom, CM1 7ET
  • Dudley, United Kingdom, DY1 2HQ
  • Eastbourne, United Kingdom, BN21 2UD
  • Gillingham, United Kingdom, ME7 5NY
  • Harrogate, United Kingdom, HG2 7SX
  • Ipswich, United Kingdom, IP4 5PD
  • Liverpool, United Kingdom, L9 7AL
  • Llantrisant, United Kingdom, CF72 8XR
  • London, United Kingdom, E11 1NR
  • Londonderry, United Kingdom, BT47 6SB
  • Maidstone, United Kingdom, ME16 9QQ
  • Middlesborough, United Kingdom, TS4 3BW
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
  • Nottingham, United Kingdom, NG5 1PB
  • Reading, United Kingdom, RG1 5AN
  • Salford, United Kingdom, M6 8HD
  • Sheffield, United Kingdom, S10 2JF
  • Southport, United Kingdom, PR8 6PN
  • Swindon, United Kingdom, SN3 6BB
  • Torquay, United Kingdom, TQ2 7AA
  • Westcliffe-on-sea, United Kingdom, SS0 0RY
  • Wirral, United Kingdom, CH49 5PE
  • Worthing, United Kingdom, BN11 2DH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- patients who completed the 24-week MA21573 core study, had at least a moderate response based on EULAR definition criteria and no adverse events (AEs), serious adverse events (SAEs) or conditions that led to unacceptable risk of continued treatment.

Exclusion Criteria:

-as for MA21573.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tocilizumab; Participants received tocilizumab 8 mg/kg intravenous (IV), maximum dose not exceeding 800 mg in a single infusion, every 4 weeks for up to 104 weeks or up to 4 weeks after tocilizumab became commercially available in the respective country whichever occurred first.	Drug: tocilizumab [RoActemra/Actemra]; 8 mg/kg IV (maximum dose not exceeding 800 mg in a single infusion) every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE 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 and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. The percentage of participants with AEs and SAEs that occurred in the Extension Study grouped according to the number of disease-modifying anti-rheumatic drugs (DMARD) a participant was taking at Core Baseline is presented.	108 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events Leading to Withdraw	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 and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events.	108 Weeks
Time to Withdrawal Due to an Adverse Event (AE)	Time to withdrawal was defined as the number of days from Core Study Day 1 to the first date of onset of the AE leading to discontinuation of tocilizumab.	108 Weeks
Percentage of Participants With Discontinuation of Treatment Due to Any Cause	Percentage of participants who discontinued treatment with tocilizumab for any reason.	108 Weeks
Time to Discontinuation of Tocilizumab Treatment for Any Cause	Time in days from start of the Core Study Day 1 to discontinuation of tocilizumab for any reason.	108 Weeks
Percentage of Participants With Marked Lipid Abnormalities	Fasting blood samples were collected for Lipids: Cholesterol, Triglyceride, High-density lipoprotein (HDL) Cholesterol, Low-density lipoprotein (LDL) Cholesterol every 12 weeks and at follow-up in the Extension study and were sent to a central laboratory for analysis. Lipid abnormalities were defined as a High Cholesterol, High Triglyceride, Low HDL Cholesterol and a High LDL Cholesterol that occurred at any time in the extension study.	108 Weeks
Percentage of Participants With Adverse Events (AEs) of Special Interest	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 and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. Adverse Events of special interest for this study were: Infections (preferred term in the infection adverse event group term), Serious Infections (an infection that qualified as Serious Adverse Event), Infusion Reactions (occurred during infusion or within 24 hours of infusion), Major Cardiac AE (Myocardial Infarction/ Acute Coronary Syndrome), Stroke or Death.	108 Weeks
Percentage of Participants With ALT Elevations > 3*ULN	Blood samples were collected for the Liver Function Test: Alanine aminotransferase (ALT) every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. Percentage of participants with any values greater than 3 times the Upper Limit of Normal (3*ULN) is reported. ULN= 55 Units/Liter.	108 Weeks
Percentage of Participants With AST Elevations > 3*ULN	Blood was collected for the Liver Function Test: Aspartate aminotransferase (AST) every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. Percentage of participants with any values greater than 3 times the Upper Limit of Normal (3*ULN) is reported. ULN= 40 Units/Liter.	108 Weeks
Number of Participants Categorized by Highest Value for ALT (SGPT) During the Study	Blood samples were collected for liver function test: Alanine aminotransferase (serum glutamic-pyruvic transaminase) [ALT(SGPT)] every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. The Upper Limit of Normal (ULN) for ALT=55 Units/Liter. The number of participants categorized by the highest value for ALT/GPT during the study is reported: Normal (ALT result within the central lab reference range), Greater than the ULN to 1.5 times the ULN (>ULN to 1.5*ULN), 1.5 times the ULN to 3 times the ULN (1.5*ULN to 3*ULN) and 3 times the ULN to 5 times the ULN (3*ULN to 5*ULN).	108 Weeks
Number of Participants Categorized by Worst Value for AST (SGOT) During the Study	Blood samples were collected for liver function test: Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase) [AST (SGOT)] every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. The Upper Limit of Normal (ULN) for AST=40 Units/Liter. The number of participants categorized by worst value for AST(SGOT) during the study is reported: Normal (AST result is within the central lab reference range), Greater than the ULN to 1.5 times the ULN (>ULN to 1.5*ULN), 1.5 times the ULN to 3 times the ULN (1.5*ULN to 3*ULN) and 3 times the ULN to 5 times the ULN (3*ULN to 5*ULN).	108 Weeks
Number of Participants Categorized by Worst Value for LDL Cholesterol During the Study	Blood samples were collected for LDL Cholesterol every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. The number of participants categorized by the worst value for LDL Cholesterol during the study is reported: Low is below central lab reference range, Normal is within the central lab reference range and High is above central lab reference range.	108 Weeks
Number of Participants Categorized by Worst Value for Total Cholesterol During the Study	Blood samples were collected for Total Cholesterol every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. The number of participants categorized by worst value for Total Cholesterol during the study is reported: Low is below central lab reference range, Normal is within the central lab reference range and High is above central lab reference range.	108 Weeks
Number of Participants Categorized by Worst Value for Neutrophil Count During the Study	Blood samples were collected for a Neutrophil Count every 12 weeks and at the follow-up visit in the Extension study and were sent to a central laboratory for analysis. The number of participants categorized by the worst value for Neutrophil Count during the study is reported: Low is below central lab reference range, Normal is within the central lab reference range and High is above central lab reference range.	108 Weeks
Percentage of Participants With Clinically Meaningful Improvement in Disease Activity Score-28 (DAS28)	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. Clinical meaningful improvement was defined as a ≥ 1.2 unit reduction in DAS28.	Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108
Percentage of Participants With DAS28 Low Disease Activity	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. Low Disease Activity was defined as a score of < 3.2.	Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108
Percentage of Participants With DAS28 Remission	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 was defined as a DAS28 score < 2.6.	Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108
Change From Baseline in DAS28	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.	Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108
Change From Baseline in Tender Joint Count	68 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement.	Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108
Change From Baseline in Swollen Joint Count	66 joints were assessed for swelling and joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement.	Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108
Change From Baseline in Patient Assessment of Pain Visual Analog Scale (VAS)	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.	Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108
Change From Baseline in Patient Global Assessment of Disease Activity VAS	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 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.	Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108
Change From Baseline in Physician Global Assessment of Disease Activity VAS	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.	Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108
Change From Baseline in Erythrocyte Sedimentation Rate (ESR)	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.	Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108
Change From Baseline in C-Reactive Protein (CRP)	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.	Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108
Percentage of Participants With American College of Rheumatology 20 (ACR20) Response	ACR20 response was 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].	Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108
Percentage of Participants With American College of Rheumatology 50 (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].	Core Baseline, Extension Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108
Percentage of Participants With American College of Rheumatology 70 (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].	Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108
Percentage of Participants With American College of Rheumatology 90 (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].	Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Response	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.	Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108
Percentage of Participants Achieving Clinical Meaningful Health Assessment Questionnaire Disability Index (HAQ-DI) Response	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). Clinically meaningful improvement is defined as a reduction from Baseline in the HAQ-DI score ≥ 0.2.	Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108
Percentage of Participants Achieving Health Assessment Questionnaire Disability Index (HAQ-DI) Clinical Remission	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). Clinical Remission is defined as a HAQ-DI score < 0.5.	Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108
Change From Baseline in Quality of Life Short Form (SF-36): Physical Component Score	The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from Baseline indicated improvement.	Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108
Change From Baseline in Quality of Life Short Form (SF-36):Mental Component Score	The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from Baseline indicated improvement.	Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108
Change From Baseline in FACIT-Fatigue Score	FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status. A positive change from Baseline indicated improvement.	Core Baseline, Extension Weeks 12, 24, 36 ,48, 60, 72, 84, 96, 108

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: April 17, 2009
• First Submitted That Met QC Criteria: April 17, 2009
• First Posted (Estimate): April 20, 2009

Study Record Updates

• Last Update Posted (Estimate): August 6, 2014
• Last Update Submitted That Met QC Criteria: August 4, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: MA22460; 2008-006924-68