- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02046603
A Study of Tocilizumab (RoActemra/Actemra) in Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Participants With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-TNF Biologic Agent (ACT-MOVE)
May 25, 2018 updated by: Hoffmann-La Roche
Open-Label, Phase IIIb Study to Evaluate the Efficacy and Safety of Subcutaneous (SC) Tocilizumab Monotherapy or Combination Therapy With Methotrexate (MTX) or Other Non-Biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) in Patients With Active Rheumatoid Arthritis (RA) Who Have an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-Tumour Necrosis Factor (Anti-TNF) Biologic Agent
This open-label study will evaluate the efficacy and safety of tocilizumab as monotherapy or in combination with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) in participants with active rheumatoid arthritis (RA) and an inadequate response to current non-biologic DMARD therapy or the first anti-tumour necrosis factor (anti-TNF) agent.
Participants will receive tocilizumab 162 milligrams (mg) subcutaneously once a week for 52 weeks.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
162
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Aberdeen, United Kingdom, AB25 2ZN
- Aberdeen Royal Infirmary
-
Bournemouth, United Kingdom, BH23 2JX
- Christchurch Hospital; Rheumatology
-
Brighton, United Kingdom, BN2 5BE
- Royal Sussex County Hospital; Clinical Investigation Research Unit
-
Burton on Trent, United Kingdom, DE13 0RB
- Queens Hospital
-
Bury Saint Edmonds, United Kingdom, IP33 2QZ
- West Suffolk Hospital
-
Cambridge, United Kingdom, CB2 2QQ
- Addenbrooke'S Hospital; Rheumatology Research Unit
-
Cannock, United Kingdom, WS11 5XY
- Cannock Chase Hospital; Rheumatology
-
Cardiff, United Kingdom, CF14 4XW
- University Hospital of Wales; Dept of Rhematology
-
Chelmsford, United Kingdom, CM1 7ET
- Broomfield Hospital
-
Chester, United Kingdom, CH2 1UL
- Countess of Chester Hospital; Dept of Rheumatology
-
Dewsbury, United Kingdom, WF13 4HS
- Dewsbury & District Hospital; Dept of Rheumatology
-
Dudley, United Kingdom, DY1 2HQ
- Russells Hall Hospital; Rheumatology Department
-
Dundee, United Kingdom, DD12 9SY
- Ninewells Hospital
-
Eastbourne, United Kingdom, BN21 2UD
- Eastbourne District General Hospital; Dept of Rheumatology
-
Edinburgh, United Kingdom, EH4 2XU
- Western General Hospital; Pharmacy Department
-
Glasgow, United Kingdom, G12 0YN
- Gartnavel General Hospital; Rheumatology
-
Grimsby, United Kingdom, DN33 2BA
- Diana Princess of Wales Hosp.
-
Harlow, United Kingdom, CM20 1QX
- Princess Alexandra Hospital
-
Harrow, United Kingdom, HA1 3UJ
- Northwick Park Hospital
-
Hemel Hempstead, United Kingdom, HP2 4AD
- Hemel Hempstead General Hospital; Rheumatology Dept
-
Hull, United Kingdom, HU3 3JZ
- Hull Royal Infirmary; Rheumatology Department
-
Llandudno, United Kingdom, LL30 1LB
- Llandudno General Hospital
-
London, United Kingdom, E11 1NR
- Whipps Cross Hospital; Rheumatology Dept
-
London, United Kingdom, NW3 2QG
- Royal Free Hospital; Department of Rheumatology
-
Maidstone, United Kingdom, ME16 9QQ
- Maidstone Hospital; Dept of Rheumatology
-
Manchester, United Kingdom, M23 9QZ
- Wythenshawe Hospital
-
Newcastle Upon Tyne, United Kingdom, NE7 7DN
- Freeman Hospital; Dept of Rheumatology
-
North Shields, United Kingdom, NE29 8NH
- North Tyneside General Hospital
-
Norwich, United Kingdom, NR4 7UY
- Norfolk & Norwich Hospital; Rheumatology
-
Oldham, United Kingdom, OL1 1NL
- Integrated Care Centre
-
Solihull, United Kingdom, B91 2JL
- Solihull Hospital
-
Stoke-on-trent, United Kingdom, ST6 7AG
- Haywood Hospital; Staffordshire Rheumatology Centre
-
Swindon, United Kingdom, SN3 6BB
- Great Western Hospital; Dept of Rheumatology
-
Torquay, United Kingdom, TQ2 7AA
- Torbay Hospital; Dept of Rhematology
-
Truro, United Kingdom, TR1 3LJ
- Royal Cornwall Hospital; Rhuematololgy Dept
-
Warrington, United Kingdom, WA5 1QG
- Warrington Hospital
-
Wigan, United Kingdom, WN6 9EW
- Wrightington Hospital; Rheumatology
-
Wishaw, United Kingdom, ML2 0DP
- Wishaw General Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria
- Participants who have an inadequate response to current non-biologic DMARD therapy or the first anti-TNF agent (in monotherapy or in combination with MTX or other non-biologic DMARDs). Inadequate response to anti-TNF treatment is defined as DAS28 score improvement of less than 1.2 or participants achieving a DAS28 score improvement of 1.2 but not achieving low disease activity (current DAS28-ESR above 3.2) according to a treat-to-target strategy and have not been previously exposed to treatment with tocilizumab. Inadequate response to non-biologic DMARD therapy will be assessed according to local guidelines and the participants will need to be eligible for biologic therapy according to local guidelines
- Oral corticosteroids (≤10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to recommended dose) are permitted if on stable dose regimen for greater than or equal to [≥] 4 weeks prior to baseline
- Permitted non-biologic DMARDs are allowed if on stable dose for at least 4 weeks prior to baseline
- Receiving treatment on an outpatient basis, not including tocilizumab
- Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception as defined by protocol during the study and for at least 3 months following the last dose of tocilizumab
Exclusion Criteria:
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline
- Rheumatic autoimmune disease other than RA
- Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
- Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16
- Prior history of or current inflammatory joint disease other than RA
- Exposure to tocilizumab either intravenous or SC at any time prior to baseline
- Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
- Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
- History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
- Known active current or history of recurrent infections
- Major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening
- Active tuberculosis (TB) requiring treatment within the previous 3 years
- Positive for hepatitis B or hepatitis C virus infection
- Primary or secondary immunodeficiency (history of or currently active)
- Pregnant or lactating women
- Inadequate hematologic, renal or liver function
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Tocilizumab Monotherapy
Participants will receive a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.
|
Tocilizumab 162 mg will be administered once a week by SC injection and as a single fixed dose, irrespective of body weight, for the treatment duration of 52 weeks.
Other Names:
|
Experimental: Tocilizumab in Combination With Methotrexate or Other DMARDs
Participants will receive a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.
|
Tocilizumab 162 mg will be administered once a week by SC injection and as a single fixed dose, irrespective of body weight, for the treatment duration of 52 weeks.
Other Names:
Treatment with non-biologic DMARDs, at a stable dose that was initiated at least 4 weeks prior to baseline, is permitted during the study.
The study protocol does not specify any particular therapy.
Stable oral corticosteroids doses (≤10 mg/day prednisone or equivalent) are allowed.
The study protocol does not specify any additional detail on types of oral corticosteroids.
Methotrexate per investigator's discretion.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 2
Time Frame: Baseline, Week 2
|
DAS28 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, erythrocyte sedimentation rate (ESR; millimeters per hour [mm/hour]), and patient's global assessment of disease activity (measured on a 0 to 100 mm Visual Analog Scale [VAS] where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR greater than or equal to (≥) 2.6 to less than or equal to (≤) 3.2 implied low disease activity, greater than (>) 3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and less than (<) 2.6 implied clinical remission.
|
Baseline, Week 2
|
Change From Baseline in DAS28-ESR at Week 4
Time Frame: Baseline, Week 4
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, Week 4
|
Change From Baseline in DAS28-ESR at Week 8
Time Frame: Baseline, Week 8
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, Week 8
|
Change From Baseline in DAS28-ESR at Week 12
Time Frame: Baseline, Week 12
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, Week 12
|
Change From Baseline in DAS28-ESR at Week 16
Time Frame: Baseline, Week 16
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, Week 16
|
Change From Baseline in DAS28-ESR at Week 20
Time Frame: Baseline, Week 20
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, Week 20
|
Change From Baseline in DAS28-ESR at Week 24
Time Frame: Baseline, Week 24
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, Week 24
|
Change From Baseline in DAS28-ESR at Week 28
Time Frame: Baseline, Week 28
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, Week 28
|
Change From Baseline in DAS28-ESR at Week 32
Time Frame: Baseline, Week 32
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, Week 32
|
Change From Baseline in DAS28-ESR at Week 36
Time Frame: Baseline, Week 36
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, Week 36
|
Change From Baseline in DAS28-ESR at Week 40
Time Frame: Baseline, Week 40
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, Week 40
|
Change From Baseline in DAS28-ESR at Week 44
Time Frame: Baseline, Week 44
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, Week 44
|
Change From Baseline in DAS28-ESR at Week 48
Time Frame: Baseline, Week 48
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, Week 48
|
Change From Baseline in DAS28-ESR at Week 52
Time Frame: Baseline, Week 52
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, Week 52
|
Change From Baseline in DAS28-ESR at Early Withdrawal
Time Frame: Baseline, early withdrawal (up to Week 52)
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity, >3.2 to ≤5.1 implied moderate disease activity, >5.1 implied high/severe disease, and <2.6 implied clinical remission.
|
Baseline, early withdrawal (up to Week 52)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
A participant had an ACR20 response if there was at least a 20 percent (%) improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either C-reactive protein [CRP] or ESR).
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Number of Participants Achieving an ACR50 Response
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
A participant had an ACR50 response if there was at least a 50% improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Number of Participants Achieving an ACR70 Response
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
A participant had an ACR70 response if there was at least a 70% improvement, ie, reduction from Baseline, in TJC (68 joints) and SJC (66 joints) and in at least 3 of the following 5 parameters: 1) Physician's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 2) Patient's Global Assessment of Disease Activity [VAS: 0 mm=no disease activity to 100 mm=maximum disease activity]; 3) Patient's Assessment of Pain [VAS: 0 mm=no pain to 100 mm=unbearable pain]; 4) Health Assessment Questionnaire [20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, averaged to 0=without difficulty to 3=unable to do] and 5) an acute-phase reactant (either CRP or ESR).
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Number of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
DAS28-ESR was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (VAS: 0 mm=no disease activity to 100 mm=maximum disease activity).
DAS28-ESR scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
The DAS28-ESR based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached.
Good responders had a change from baseline >1.2 with a DAS28 score ≤3.2; moderate responders had a change from baseline >1.2 with a DAS28 score >3.2 or a change from baseline >0.6 to ≤1.2 with a DAS28 score ≤5.1.
Participants with change from baseline >0.6 to ≤1.2 with a DAS28 score >5.1, or any score with change from baseline ≤0.6, were assessed as non-responders.
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
The SDAI is the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician global assessment of disease activity assessed on 0-10 centimeter (cm) VAS (0 cm= no disease activity and 10 cm= worst disease activity), and CRP in milligrams per liter (mg/L).
SDAI total score = 0-86.
SDAI ≤3.3 indicates clinical remission, >3.3 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity.
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
The CDAI is the numerical sum of four outcome parameters: TJC and SJC based on a 28-joint assessment, patient and physician's global assessment of disease activity assessed on 0-10 cm VAS (0 cm= no disease activity and 10 cm= worst disease activity).
CDAI total score = 0-76.
CDAI ≤2.8 indicates clinical remission, >2.8 to 10 = low disease activity, >10 to 22 = moderate disease activity, and >22 = high (or severe) disease activity.
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Percent Change From Baseline in Total TJC on 68 Joints at Week 52
Time Frame: Baseline, Week 52
|
Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion.
The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 68.
A reduction in number of tender joints compared to baseline indicates improvement.
The outcome is reported as the percent change from baseline to end of treatment (52 weeks).
|
Baseline, Week 52
|
Change From Baseline in Total TJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion.
The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1; total was calculated by adding all the joints for a maximum score of 28.
A reduction in number of tender joints compared to baseline indicates improvement.
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Percent Change From Baseline in Total SJC on 66 Joints at Week 52
Time Frame: Baseline, Week 52
|
Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present.
The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 66.
A reduction in number of swollen joints compared to baseline indicates improvement.
The outcome is reported as the percent change from baseline to end of treatment (52 weeks).
|
Baseline, Week 52
|
Change From Baseline in Total SJC on 28 Joints at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Early Withdrawal
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present.
The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1; total was calculated by adding all the joints for a maximum score of 28.
A reduction in number of swollen joints compared to baseline indicates improvement.
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Number of Participants Who Achieved Low Disease Activity as Defined by DAS28-ESR ≤3.2
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR ≥2.6 to ≤3.2 implied low disease activity.
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Number of Participants Who Achieved Remission as Defined by DAS28-ESR <2.6
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour), and patient's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0 mm=no disease activity and 100 mm=worst disease activity).
DAS28 scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS].
Total score range: 0-10, higher score=higher disease activity.
DAS28-ESR <2.6 implied clinical remission.
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Number of Participants With Non-Biologic DMARD/Corticosteroid Dose Reductions and/or Discontinuation
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, at early withdrawal (up to Week 52), follow-up Week 4 (up to Week 56), and follow-up Week 8 (up to Week 60)
|
Results are reported for number of participants who had non-biologic DMARD/corticosteroid dose reductions and/or discontinuation by reasons for dose reductions or discontinuation (safety reasons, discomfort, lack of efficacy, other reasons, and unknown reasons).
Participants may be included under more than one reason.
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, at early withdrawal (up to Week 52), follow-up Week 4 (up to Week 56), and follow-up Week 8 (up to Week 60)
|
Percentage of Methotrexate Adherence as Assessed by Methotrexate Adherence Questionnaire
Time Frame: Baseline, Weeks 12, 24, 36, 52, and at early withdrawal (up to Week 52)
|
Methotrexate adherence was determined from responses to the question 'Over the last 3 months you were prescribed 12 doses of methotrexate, how many (approximately) have you taken?' Adherence (%) was calculated as: (Approximate number of doses taken/12)*100.
|
Baseline, Weeks 12, 24, 36, 52, and at early withdrawal (up to Week 52)
|
Patient Global Assessment of Disease Activity VAS Score
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Patient global assessment of disease activity was measured on a 0 to 100 mm horizontal VAS where 0 mm=no disease activity and 100 mm=maximum disease activity.
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Patient Pain VAS Score
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
This assessment represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS where 0 mm= no pain to 100 mm= unbearable pain.
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
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.
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
The FACIT-F score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function.
FACIT-F is a 13-item questionnaire.
Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much).
The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant'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 participant's response).
The sum of all responses resulted in the FACIT-F score for a total possible score of 0 (worse score) to 52 (better score).
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Number of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records
Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
A diary card was provided to participants to record home injections.
Participants were asked to return all empty drug supply boxes, unused pre-filled syringe, and diary cards to the clinic at each visit as a measure of drug accountability and participant compliance.
A participant was considered compliant if the participant correctly administered all scheduled doses of SC tocilizumab during the assessment period.
|
Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at early withdrawal (up to Week 52)
|
Number of Participants With Anti-Tocilizumab Antibodies
Time Frame: Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)
|
Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)
|
|
Serum Levels of Tocilizumab
Time Frame: Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)
|
Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)
|
|
Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)
Time Frame: Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)
|
Baseline, Weeks 12 and 24, at early withdrawal (up to Week 52), and follow-up visit (8 weeks after last dose of tocilizumab, up to 60 weeks)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Devenport J, Petho-Schramm A. Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis. Rheumatology (Oxford). 2019 Jun 1;58(6):1056-1064. doi: 10.1093/rheumatology/key393.
- Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Bernasconi C, Petho-Schramm A. Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries. Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. doi: 10.1093/rheumatology/kex443. Erratum In: Rheumatology (Oxford). 2018 Jun 1;57(6):1129.
- Isaacs JD, Salih A, Sheeran T, Patel YI, Douglas K, McKay ND, Naisbett-Groet B, Choy E. Efficacy and safety of subcutaneous tocilizumab in rheumatoid arthritis over 1 year: a UK real-world, open-label study. Rheumatol Adv Pract. 2019 Apr 19;3(1):rkz010. doi: 10.1093/rap/rkz010. eCollection 2019.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 4, 2014
Primary Completion (Actual)
August 4, 2016
Study Completion (Actual)
August 4, 2016
Study Registration Dates
First Submitted
January 24, 2014
First Submitted That Met QC Criteria
January 24, 2014
First Posted (Estimate)
January 28, 2014
Study Record Updates
Last Update Posted (Actual)
December 7, 2018
Last Update Submitted That Met QC Criteria
May 25, 2018
Last Verified
May 1, 2018
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
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Methotrexate
Other Study ID Numbers
- ML28641
- 2013-000054-22 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Rheumatoid Arthritis
-
Janssen Research & Development, LLCWithdrawnActive Rheumatoid Arthritis; Rheumatoid Arthritis
-
Centocor, Inc.CompletedRheumatoid Arthritis, Juvenile
-
AmgenTerminated
-
Children's Hospital Medical Center, CincinnatiNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)CompletedJuvenile Rheumatoid ArthritisUnited States
-
AmgenImmunex CorporationCompletedJuvenile Rheumatoid Arthritis
-
Assistance Publique - Hôpitaux de ParisSociete Francaise de RhumatologieRecruiting
-
Amsterdam UMC, location VUmcEuropean CommissionCompletedRheumatoId ArthritisNetherlands, Germany, Portugal, Italy, Hungary, Romania, Slovakia
-
University Hospital, ToulouseCompletedRheumatoId ArthritisFrance
-
David Grant U.S. Air Force Medical CenterCompleted
-
TcLand Expression S.A.European CommissionTerminatedRheumatoId ArthritisFrance, Netherlands, Turkey, Czechia, Israel
Clinical Trials on Tocilizumab
-
University of ChicagoActive, not recruiting
-
CelltrionNot yet recruiting
-
University of ChicagoRecruiting
-
Reade Rheumatology Research InstituteZonMw: The Netherlands Organisation for Health Research and DevelopmentRecruitingRheumatoid ArthritisNetherlands
-
Memorial Sloan Kettering Cancer CenterTerminatedCOVID-19United States
-
University of ChicagoCompleted
-
Karadeniz Technical UniversityCompletedCOVID-19 | Mortality | Critical Care | TocilizumabTurkey
-
Assistance Publique - Hôpitaux de ParisUnknown
-
Università Politecnica delle MarcheAzienda Ospedaliera Ospedali Riuniti Marche NordUnknown
-
Hospital of PratoUnknown