Clinical Trial Results:
TOSCARA: An open-label, single-arm study to evaluate the efficacy, safety and tolerability of tocilizumab (TCZ) subcutaneous in TCZ-naïve patients with active rheumatoid arthritis
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Summary
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EudraCT number |
2013-002150-79 |
Trial protocol |
BE |
Global end of trial date |
03 Sep 2015
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Results information
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Results version number |
v2(current) |
This version publication date |
26 Aug 2017
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First version publication date |
17 Nov 2016
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ML28701
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02031471 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Alias: TOSCARA | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Sep 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Sep 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the efficacy of subcutaneous (SC) tocilizumab (TCZ) monotherapy and/or in combination with methotrexate (MTX) or other non-biologic disease modifying antirheumatic drugs (DMARDs) using change of Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24.
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Protection of trial subjects |
All study subjects were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Jan 2014
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
2 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 52
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Country: Number of subjects enrolled |
Luxembourg: 5
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Worldwide total number of subjects |
57
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EEA total number of subjects |
57
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
45
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From 65 to 84 years |
12
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 62 subjects were screened, 57 subjects were enrolled. Subjects who completed the 24 Week Treatment Period achieving at least a moderate European League Against Rheumatism (EULAR) response at Week 24 were allowed to enter the Long Term Extension (LTE) Period. | ||||||||||||||||||
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Period 1
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Period 1 title |
24 Week Treatment Period
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Tocilizumab | ||||||||||||||||||
Arm description |
Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the long term extension (LTE) period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 milligram (mg) tocilizumab was administered subcutaneously once weekly. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Tocilizumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received fixed dose of 162 mg SC weekly.
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Period 2
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Period 2 title |
Long Term Extension (LTE) Period
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Tocilizumab | ||||||||||||||||||
Arm description |
Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the long term extension (LTE) period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 milligram (mg) tocilizumab was administered subcutaneously once weekly. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Tocilizumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received fixed dose of 162 mg SC weekly.
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| Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: Only subjects who achieved at least a moderate EULAR response at Week 24 entered the LTE Period. |
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Baseline characteristics reporting groups
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Reporting group title |
Tocilizumab
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Reporting group description |
Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the long term extension (LTE) period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 milligram (mg) tocilizumab was administered subcutaneously once weekly. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tocilizumab
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Reporting group description |
Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the long term extension (LTE) period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 milligram (mg) tocilizumab was administered subcutaneously once weekly. | ||
Reporting group title |
Tocilizumab
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Reporting group description |
Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the long term extension (LTE) period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 milligram (mg) tocilizumab was administered subcutaneously once weekly. | ||
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End point title |
Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Full Analysis Set (FAS) [1] | ||||||||||||
End point description |
The DAS28 score is a measure of the subject's disease activity calculated using the tender joint count of 28 joints (TJC28), swollen joint count of 28 joints (SJC28), patient's global assessment of disease activity visual analog scale (PGA VAS) with 0=no disease activity to 100=maximum disease activity displayed on the 100-millimeter (mm) horizontal VAS and acute phase reactant (erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]) for a total possible score of 0 to 10. For this study ESR was used to calculate the DAS28 score. The index is calculated using the following formula: DAS28 = (0.56*√[TJC28]) + (0.28*√[SJC28]) + (0.70*ln[ESR]) + (0.014*VAS). Higher scores represent higher disease activity. A negative change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Primary
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End point timeframe |
From baseline to Week 24
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for the endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Per Protocol Set (PPS) [2] | ||||||||||||
End point description |
The DAS28 score is a measure of the subject's disease activity calculated using the TJC28, SJC28, PGA VAS with 0=no disease activity to 100=maximum disease activity displayed on the 100-mm horizontal VAS and acute phase reactant (ESR or CRP) for a total possible score of 0 to 10. For this study ESR was used to calculate the DAS28 score. The index is calculated using the following formula: DAS28 = (0.56*√[TJC28]) + (0.28*√[SJC28]) + (0.70*ln[ESR]) + (0.014*VAS). Higher scores represent higher disease activity. A negative change from baseline indicates an improvement. The PPS consisted of all subjects of the FAS having a value at baseline and at Week 24 for the endpoint DAS28-ESR, excluding sponsor defined deviation(s) which could have affected the evaluation of the primary endpoint (DAS28-ESR). Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Primary
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End point timeframe |
From baseline to Week 24
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be reported for the endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects With Positive American College of Rheumatology (ACR) Response Scores | ||||||||||||||||||||||||||||||||
End point description |
The ACR core set of outcome measures and their definition of improvement includes a >= 20% improvement (ACR20) compared to Baseline in both SJC and TJC as well as in three out of five additional parameters: Physician's Global Assessment of disease activity VAS, PGA VAS, patient's assessment of pain VAS, Health Assessment Questionnaire-Disability Index (HAQ-DI), and acute phase reactant (CRP or ESR). VAS range for all assessments was 0=no disease activity to 100=maximum disease activity displayed on the 100-mm horizontal VAS. Achievement of an ACR50 requires a >= 50% improvement in the same parameters and an ACR70 requires a >= 70% improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 2, Week 24, and Week 52
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects With Responses According to European League Against Rheumatism (EULAR ) Criteria | ||||||||||||||||||||
End point description |
EULAR response was calculated as the difference between DAS28-ESR scores at baseline and Week 24, and reported as the percentage of subjects with good, moderate, or no response. Good responders = decrease from baseline >1.2 with a DAS28 score of <=3.2; moderate responders = decrease from baseline >1.2 with a DAS28 score of >3.2, or decrease from baseline >0.6 to <=1.2 with a DAS28 score of <=5.1; non-responders = decrease from baseline <=0.6 or decrease from baseline >0.6 and <=1.2 with a DAS28 score of >5.1. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 2, Week 24
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI) | ||||||||||||||||||||||||
End point description |
SDAI is a similar index to DAS28 but has the advantage of not needing a complicated mathematical formula for its determination, but a simple arithmetical addition of TJC28 and SJC28, PGA VAS and Physician Global Assessment of disease activity VAS, and CRP concentration in mg/L. CDAI does not incorporate an acute response, therefore it can be used to evaluate disease activity in the absence of laboratory testing of CRP and ESR. VAS range for all assessments was 0=no disease activity to 100=maximum disease activity displayed on the 100-mm horizontal VAS. SDAI scores ranged from 0 to 86, CDAI from 0 to 76 with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Change in Total Tender/Swollen Joint Counts (TJC/SJC) | ||||||||||||||||||||||||
End point description |
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation on physical examination. Joint prosthesis, arthrodesis or fused joints were not taken into consideration for swelling or tenderness. A negative change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Percentage of Subjects With Corticosteroid Dose Reduction/Discontinuation | ||||||||
End point description |
The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab.
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End point type |
Secondary
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End point timeframe |
Up to Week 52
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| Notes [3] - Number of subjects analysed signifies those subjects who were evaluable for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity | ||||||||||||||||||||||||||||||||||||||||
End point description |
CDAI is calculated by simple arithmetical addition of TJC28 and SJC28, PGA VAS and Physician Global Assessment of disease activity VAS. VAS range was 0=no disease activity to 100=maximum disease activity displayed on the 100-mm horizontal VAS. Total CDAI score ranges from 0 to 76 with higher scores indicating increased disease activity. Clinical remission = score ≤ 2.8; Low disease activity = score > 2.8 and ≤ 10.0; Moderate disease activity = score > 10.0 and ≤ 22.0; High disease activity = score > 22.0. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline to Week 2, Week 24 and Week 52
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity | ||||||||||||||||||||||||||||||||||||||||
End point description |
SDAI is calculated by simple arithmetical addition of TJC28 and SJC28, PGA VAS and Physician Global Assessment of disease activity VAS, and CRP concentration in mg/L. VAS range was 0=no disease activity to 100=maximum disease activity displayed on the 100-mm horizontal VAS. Total SDAI score ranges from 0 to 86 with higher scores indicating increased disease activity. Clinical remission = score ≤ 3.3; Low disease activity = score > 3.3 and ≤ 11.0; Moderate disease activity = score > 11.0 and ≤ 26.0; high disease activity = score > 26.0. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity | ||||||||||||||||||||||||||||||||||||||||
End point description |
The DAS28 score is a measure of the subject's disease activity calculated using TJC28, SJC28, PGA VAS with 0=no disease activity to 100=maximum disease activity displayed on the 100-millimeter (mm) horizontal VAS and acute phase reactant (erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]) for a total possible score of 0 to 10. For this study ESR was used to calculate the DAS28 score. The index is calculated using the following formula: DAS28 = (0.56*√[TJC28]) + (0.28*√[SJC28]) + (0.70*ln[ESR]) + (0.014*VAS). Higher scores represent higher disease activity. Clinical remission = score <2.6; Low disease activity = score ≥2.6 and ≤3.2; Moderate disease activity = score > 3.2 and ≤5.1; High disease activity = score >5.1. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects Achieving a Clinically Significant Improvement in DAS28 | ||||||||||||||
End point description |
The DAS28 score is a measure of the subject's disease activity calculated using TJC28, SJC28, PGA VAS with 0=no disease activity to 100=maximum disease activity displayed on the 100-millimeter (mm) horizontal VAS and acute phase reactant (erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]) for a total possible score of 0 to 10. For this study ESR was used to calculate the DAS28 score. The index is calculated using the following formula: DAS28 = (0.56*√[TJC28]) + (0.28*√[SJC28]) + (0.70*ln[ESR]) + (0.014*VAS). Higher scores represent higher disease activity. DAS28 Clinically Significant Improvement was defined as a DAS28 score reduction of at least 1.2 units from Baseline. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change From Baseline in Physician’s Global Assessment of Disease Activity VAS | ||||||||||||||||
End point description |
Physician's Global Assessment of disease activity VAS represents the physician's assessment of the subject's current disease activity on a 100 mm horizontal VAS. The extreme left end of the line represents 0= "no disease activity" (symptom-free and no arthritis symptoms) and the extreme right end 100= "maximum disease activity". This was completed by the Treating Physician (or designee). A negative change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in Patient’s Global Assessment of Disease Activity VAS | ||||||||||||||||
End point description |
PGA VAS represents the subject's overall assessment of their current disease activity on a 100 mm horizontal VAS. The extreme left end of the line represents 0= "no disease activity" (symptom-free and no arthritis symptoms) and the extreme right end 100="maximum disease activity" (maximum arthritis disease activity). A negative change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in Patient’s Assessment of Pain VAS | ||||||||||||||||
End point description |
Patient's Assessment of Pain VAS represents the subject's assessment of his/her current level of pain on a 100 mm horizontal VAS. The extreme left end of the line represents 0="no pain" and the extreme right end 100="unbearable pain". A negative change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 2 and Week 24
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Acute Phase Reactants: Change From Baseline in CRP | ||||||||||||||||
End point description |
A negative change from baseline in CRP level indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Acute Phase Reactants: Change From Baseline in ESR | ||||||||||||||||
End point description |
A negative change from baseline in ESR indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
|
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End point type |
Secondary
|
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End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
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| No statistical analyses for this end point | |||||||||||||||||
|
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End point title |
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | ||||||||||||||||
End point description |
The Stanford HAQ-DI is a patient-oriented outcome assessment questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities. Each category contains multiple questions, which were answered using a 4-point scale from 0 to 3. The overall index score was an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. A negative change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
|
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End point type |
Secondary
|
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End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
|
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) | ||||||||||||||||
End point description |
The symptom-specific measure FACIT-F was developed to assess chronic illness therapy with special emphasis on fatigue in the past 7 days. In this study, only the FACIT-F short questionnaire, which is a shorter version of the initial FACIT-F questionnaire, was used. Each of the questions is categorically answered using the scales 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. The 13 items included in the FACIT-F short can be used to calculate the brief score for FACIT-F scale (score range: 0-52). A positive change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
|
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End point type |
Secondary
|
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End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) | ||||||||||||||||
End point description |
The PSQI is a self-rated questionnaire which assesses sleep quality and disturbances over 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The subject self-rates each of these seven areas of sleep. Scoring of answers is based on a 0 to 3 scale, whereby 3 reflects the negative extreme on the Likert Scale. Global scores range from 0 to 21 and a global sum of "5" or greater indicates a "poor" sleeper. Although there are several questions that request the evaluation of the subject's bedmate or roommate, these are not scored. A negative change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
|
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End point type |
Secondary
|
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End point timeframe |
From Baseline to Week 4, Week 24 and Week 52
|
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in Patient Quality of Sleep VAS | ||||||||||||||||
End point description |
The Patient Quality of Sleep VAS assessment represents the subject's assessment of his/her current quality of sleep on a 100 mm horizontal VAS. The extreme left end of the line represents 0="no difficulty to sleep" and the extreme right end 100="extreme sleeping difficulties". A negative change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
|
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End point type |
Secondary
|
||||||||||||||||
End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
|
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|
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF) | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The AIMS-SF is a reduced version of the validated AIMS2 questionnaire. The Short Form has been developed using a comprehensive expert-based approach and supported by psychometric testing. The AIMS-SF is a self-administered questionnaire to measure changes in global health, pain, mobility and social function in adult subjects with arthritis and reports scores for physical, symptoms, affect, social and work assessments. Scores range from 0 to 10, higher scores indicating higher impact of arthritis on the assessments. A negative change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint. Here, 99999 indicates standard deviation as it was not estimable for 1 subject.
|
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End point type |
Secondary
|
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End point timeframe |
From Baseline to Week 4, Week 24 and Week 52
|
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| Notes [4] - 99999 = Standard deviation not estimable for one subject. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
|
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End point title |
Change From Baseline in Patient Fatigue VAS | ||||||||||||||||
End point description |
The patient fatigue VAS assessment represents the subject's assessment of his/her current level of fatigue on a 100 mm horizontal VAS. The extreme left end of the line represents 0="no fatigue" and the extreme right end 100="extreme fatigue". A negative change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
|
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End point type |
Secondary
|
||||||||||||||||
End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
|
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|
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| No statistical analyses for this end point | |||||||||||||||||
|
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End point title |
Change From Baseline in Patient Satisfaction VAS | ||||||||||||||||
End point description |
The Patient Satisfaction VAS assessment represents the subject's assessment of his/her current satisfaction with treatment on a 100 mm horizontal VAS. The extreme left end of the line represents 0="no satisfaction" and the extreme right end 100="extremely satisfied". A positive change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
From Baseline to Week 2, Week 24 and Week 52
|
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|
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| No statistical analyses for this end point | |||||||||||||||||
|
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End point title |
Change From Baseline in Work Instability Scale for Rheumatoid Arthritis (RA-WIS) | ||||||||||||
End point description |
The 23-item RA-WIS is a simple, validated screening tool for work instability, i.e., the consequences of a mismatch between an individual's functional ability and their work tasks. This self-administered questionnaire covers a broad range of specific work-related issues and enables monitoring the risk of work disability in rheumatoid arthritis patients. The RA-WIS is scored by summing responses from all 23 scale items. The scale ranges from 0 to 23. Cut points have been established to differentiate levels of work instability: low < 10, moderate 10-17 and high > 17. A negative change from baseline indicates an improvement. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Baseline to Week 24
|
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|
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| No statistical analyses for this end point | |||||||||||||
|
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End point title |
Treatment Satisfaction Questionnaire for Medication (TSQM ) Scores | ||||||||||||||
End point description |
The abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) derived from the TSQM Version 1.4 but without the five items of the side effects domain, is a reliable and valid measure to assess subjects' satisfaction with treatment. The TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain. Domains included are effectiveness, convenience and global satisfaction. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
|
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End point type |
Secondary
|
||||||||||||||
End point timeframe |
Week 24
|
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|
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| No statistical analyses for this end point | |||||||||||||||
|
|||||||||
End point title |
Safety: Percentage of Subjects With Adverse Events | ||||||||
End point description |
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 52 weeks
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Safety: Percentage of Subjects With Anti-tocilizumab Antibodies | ||||||||||||
End point description |
The FAS consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab. Here, n is the number of subjects with evaluable data for this endpoint.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 24
|
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|
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| No statistical analyses for this end point | |||||||||||||
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|
Adverse events information
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Timeframe for reporting adverse events |
Up to 52 weeks
|
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Adverse event reporting additional description |
The safety population consisted of all subjects included in the study who received at least one dose of subcutaneous tocilizumab.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
|
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Reporting groups
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Reporting group title |
Tocilizumab
|
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Reporting group description |
Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the LTE period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
31 Aug 2014 |
Change to inclusion criterion to allow the previous use of more than one biologic DMARD therapy. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
