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A multi-center, open-label single-arm study to evaluate the efficacy and safety of tocilizumab administered as a single, weekly injection in adults with rheumatoid arthritis. Combination therapy with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) was permitted.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tocilizumab | Experimental | Adults with rheumatoid arthritis will be treated with tocilizumab for 24 weeks followed by an 8 week follow-up period without treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tocilizumab | Biological | 162 milligram (mg) administered subcutaneously once weekly for 24 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity | Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. Remission is defined as CDAI ≤2.8 and Low Disease Activity (LDA) is defined as 2.8< CDAI ≤10. | Week 24 |
| Change From Baseline in CDAI | Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement. | Baseline, Week 24 |
| Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission and SDAI Low Disease Activity | Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in milligram/liter (mg/L). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. An SDAI score of ≤ 3.3 represents clinical remission, a score of ≤ 11.0 represents low disease activity. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) and AEs of Special Interest (AESIs) | An AE is any untoward medical occurrence in a participant administered a drug 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, symptom, or disease temporally associated with the use of a drug, whether or not considered related to the drug. Preexisting conditions which worsen during a study are also considered as AEs. AESIs are AEs that occur in categories of special interest with regard to the benefit-risk profile and overall safety of a drug. The following nine categories of AESIs were identified for tocilizumab: 1) serious and/or medically significant infections, 2) myocardial infarction/acute coronary syndrome, 3) gastrointestinal perforations, 4) malignancies, 5) anaphylaxis/hypersensitivity reactions, 6) demyelinating disorders, 7) stroke, 8) serious and/or medically significant bleeding events, and 9) serious and/or medically significant hepatic events. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beer Yaacov | 6093000 | Israel | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30649524 | Derived | 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. | |
| 29244149 | Derived |
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| ID | Title | Description |
|---|---|---|
| FG000 | Tocilizumab | Adults with rheumatoid arthritis were treated with 162 milligram (mg) tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The full analysis set (FAS) included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
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| ID | Title | Description |
|---|---|---|
| BG000 | Tocilizumab | Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity | Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. Remission is defined as CDAI ≤2.8 and Low Disease Activity (LDA) is defined as 2.8< CDAI ≤10. | The analysis population included those participants from the full analysis set (FAS) for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. | Posted | Number | percentage of participants | Week 24 |
Up to Follow-up Week 32
The safety population included all enrolled participants who received at least one dose of subcutaneous tocilizumab.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tocilizumab | Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Colitis | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800 821-8590 | genentech@druginfo.com |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| C502936 | tocilizumab |
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| Week 24 |
| Change From Baseline in SDAI | Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in mg/L. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A negative change from baseline indicates an improvement. | Baseline, Week 24 |
| Change From Baseline in Disease Activity Score 28-Erythrocyte-Sedimentation Rate (DAS28-ESR) | The DAS28-ESR score is a measure of the patient's disease activity calculated using the tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), patient's global assessment (PGA) of disease activity based on visual analog scale (VAS) and the erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/hr). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total possible score ranged from 0 to 10. Higher scores represent higher disease activity. A negative change from baseline indicates an improvement. | Baseline, Week 24 |
| Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70) | An ACR20 response requires at least 20% improvement compared to baseline in SJC (based on 66 joints) and TJC (based on 68 joints) as well as at least 20% improvement in 3 of the following 5 assessments: 1) PGA pain VAS, 2) PGA VAS; 3) physician's global assessment of disease activity VAS, 4) Health Assessment Questionnaire-Disability Index (HAQ-DI) with 20 questions consisting of 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do; and 5) CRP in mg/L or ESR in mm/hr. ACR50 and ACR70 responses are defined in a similar way except that they required a 50% and 70% improvement from baseline, respectively. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). | Week 24 |
| Percentage of Participants With Good to Moderate European League Against Rheumatism (EULAR) Response | Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit. Participants with a score lesser than or equal to (</=) 3.2 and reduction of greater than (>) 1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score <=5.1 with reduction of >0.6 to <=1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to <=1.2 points, or any score with reduction <=0.6 points, were assessed as non-responders with response recorded as 'none.' | Week 24 |
| Change From Baseline in TJC and SJC | The number of tender joints (based on 68 joints) and swollen joints (based on 66 joints) were counted at each visit. TJC was determined by identifying the joints that were painful under pressure or to passive motion; no tenderness =0, tenderness =1. SJC was determined by identifying swelling; no swelling =0, swelling =1. A negative change from baseline indicates an improvement. | Baseline, Week 24 |
| Change From Baseline in Percentage of Participants on Tocilizumab Monotherapy | Participants were either on tocilizumab monotherapy or tocilizumab plus non-biologic disease modifying anti-rheumatic drugs (DMARDs). Reported here is the percentage of participants on tocilizumab monotherapy at baseline and the change from baseline at Week 24. A positive change from baseline at Week 24 indicates the percentage of participants, who discontinued DMARDs during the study. | Baseline, Week 24 |
| Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (PGA VAS) | PGA VAS represents the participant's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement. | Baseline, Week 24 |
| Change From Baseline in Patient Pain VAS | Patient Pain VAS represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement. | Baseline, Week 24 |
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) | The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities and 20 questions. Each category contains multiple questions, which were answered using a 4-point scale from 0 (without any difficulty) to 3 (unable to do). 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. | Baseline, Week 24 |
| Change From Baseline in Patient Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) | The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. 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 for a total possible FACIT-F score of 0 to 52. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. A positive change from baseline indicates an improvement. | Baseline, Week 24 |
| Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) | The HDRS is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score indicates a worse outcome. HAS is a clinician-administered assessment to measure the severity of anxiety symptoms and consists of 14 items with a total score range from 0 to 56. A higher score indicates a worse outcome. | Baseline, Week 24 |
| Up to Follow-up Week 32 |
| Percentage of Participants Who Required Dose Modifications or Discontinued Study Due to AEs | Up to Week 24 |
| Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies | Reported is the percentage of participants positive for anti-tocilizumab antibodies in the confirmatory anti-tocilizumab antibody assay, which followed an initial anti-tocilizumab screen. Participants, who withdrew from the study | Baseline, Week 24, Follow-up Week 32 and Early Withdrawal |
| Immunogenicity: Tocilizumab Levels | Week 12, Week 24, Follow-up Week 32 and Early Withdrawal |
| Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels | A positive change from Week 1 indicates an increase in sIL-6R levels. | Week 1, Week 12, Week 24, Follow-up Week 32 and Early Withdrawal |
| Beersheba |
| 8410101 |
| Israel |
| Haifa | 3109601 | Israel |
| Haifa | 3339419 | Israel |
| Haifa | 34362 | Israel |
| Jerusalem | 9112001 | Israel |
| Jerusalem | 91240 | Israel |
| Kfar Saba | 44281 | Israel |
| Petah Tikva | 4937211 | Israel |
| Petah Tikva | 4941492 | Israel |
| Ramat Gan | 5262000 | Israel |
| Ramat Gan | 5262100 | Israel |
| Tel Aviv | 6423906 | Israel |
| 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. |
| Lost to Follow-up |
|
| Physician Decision |
|
| Protocol Violation |
|
| years |
|
| Gender | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Tocilizumab | Adults with rheumatoid arthritis were treated with 162 mg tocilizumab administered subcutaneously once weekly for 24 weeks. The protocol recommended suspending the treatment after week 24 for a period of 8 weeks, according to investigators' discretion, for the purpose of drug-free immunogenicity testing. In the present study, none of the participants had their tocilizumab treatment suspended. |
|
|
| Primary | Change From Baseline in CDAI | Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index was calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter [cm] Visual Analog Scale [VAS] + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. A negative change from baseline indicates an improvement. | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 24 |
|
|
|
| Primary | Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission and SDAI Low Disease Activity | Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in milligram/liter (mg/L). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. An SDAI score of ≤ 3.3 represents clinical remission, a score of ≤ 11.0 represents low disease activity. | The analysis population included those participants from the FAS for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. | Posted | Number | percentage of participants | Week 24 |
|
|
|
| Primary | Change From Baseline in SDAI | Simplified Disease Activity Index (SDAI) was an index for measuring disease activity in RA and had a good correlation with the DAS28. The index was calculated using the following formula: SDAI: SJC28 + TJC28 + PGA (10 cm VAS) + PhGA (10 cm VAS + C-Reactive Protein (CRP) in mg/L. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A negative change from baseline indicates an improvement. | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 24 |
|
|
|
| Primary | Change From Baseline in Disease Activity Score 28-Erythrocyte-Sedimentation Rate (DAS28-ESR) | The DAS28-ESR score is a measure of the patient's disease activity calculated using the tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), patient's global assessment (PGA) of disease activity based on visual analog scale (VAS) and the erythrocyte sedimentation rate (ESR) in millimeter/hour (mm/hr). VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total possible score ranged from 0 to 10. Higher scores represent higher disease activity. A negative change from baseline indicates an improvement. | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 24 |
|
|
|
| Primary | Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70) | An ACR20 response requires at least 20% improvement compared to baseline in SJC (based on 66 joints) and TJC (based on 68 joints) as well as at least 20% improvement in 3 of the following 5 assessments: 1) PGA pain VAS, 2) PGA VAS; 3) physician's global assessment of disease activity VAS, 4) Health Assessment Questionnaire-Disability Index (HAQ-DI) with 20 questions consisting of 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do; and 5) CRP in mg/L or ESR in mm/hr. ACR50 and ACR70 responses are defined in a similar way except that they required a 50% and 70% improvement from baseline, respectively. VAS assessments involved a 10 cm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). | The analysis population included those participants from the FAS for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. | Posted | Number | percentage of participants | Week 24 |
|
|
|
| Primary | Percentage of Participants With Good to Moderate European League Against Rheumatism (EULAR) Response | Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit. Participants with a score lesser than or equal to (</=) 3.2 and reduction of greater than (>) 1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score <=5.1 with reduction of >0.6 to <=1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to <=1.2 points, or any score with reduction <=0.6 points, were assessed as non-responders with response recorded as 'none.' | The analysis population included those participants from the FAS for whom evaluable data for this outcome measure were available. The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. | Posted | Number | percentage of participants | Week 24 |
|
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| Primary | Change From Baseline in TJC and SJC | The number of tender joints (based on 68 joints) and swollen joints (based on 66 joints) were counted at each visit. TJC was determined by identifying the joints that were painful under pressure or to passive motion; no tenderness =0, tenderness =1. SJC was determined by identifying swelling; no swelling =0, swelling =1. A negative change from baseline indicates an improvement. | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure. | Posted | Mean | Standard Deviation | joint count | Baseline, Week 24 |
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|
| Primary | Change From Baseline in Percentage of Participants on Tocilizumab Monotherapy | Participants were either on tocilizumab monotherapy or tocilizumab plus non-biologic disease modifying anti-rheumatic drugs (DMARDs). Reported here is the percentage of participants on tocilizumab monotherapy at baseline and the change from baseline at Week 24. A positive change from baseline at Week 24 indicates the percentage of participants, who discontinued DMARDs during the study. | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. | Posted | Number | percentage of participants | Baseline, Week 24 |
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| Primary | Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (PGA VAS) | PGA VAS represents the participant's overall assessment of their current disease activity on a 100 millimeter (mm) horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement. | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 24 |
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| Primary | Change From Baseline in Patient Pain VAS | Patient Pain VAS represents the participant's assessment of his/her current level of pain on a 100 mm horizontal VAS scale from 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates an improvement. | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 24 |
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|
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| Primary | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) | The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities and 20 questions. Each category contains multiple questions, which were answered using a 4-point scale from 0 (without any difficulty) to 3 (unable to do). 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 included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 24 |
|
|
|
| Primary | Change From Baseline in Patient Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) | The symptom-specific measure FACIT-F assesses chronic illness therapy with special emphasis on fatigue in the past 7 days and consists of 5 dimensions: 1) physical well- being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, and 5) additional concerns. 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 for a total possible FACIT-F score of 0 to 52. The figures are reversed during score calculations, so that higher score values indicate more favorable conditions. A positive change from baseline indicates an improvement. | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 24 |
|
|
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| Primary | Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) | The HDRS is a clinician-administered depression assessment and consists of 17 items with a total score range from 0 to 54. A higher score indicates a worse outcome. HAS is a clinician-administered assessment to measure the severity of anxiety symptoms and consists of 14 items with a total score range from 0 to 56. A higher score indicates a worse outcome. | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 24 |
|
|
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| Secondary | Percentage of Participants With Adverse Events (AEs) and AEs of Special Interest (AESIs) | An AE is any untoward medical occurrence in a participant administered a drug 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, symptom, or disease temporally associated with the use of a drug, whether or not considered related to the drug. Preexisting conditions which worsen during a study are also considered as AEs. AESIs are AEs that occur in categories of special interest with regard to the benefit-risk profile and overall safety of a drug. The following nine categories of AESIs were identified for tocilizumab: 1) serious and/or medically significant infections, 2) myocardial infarction/acute coronary syndrome, 3) gastrointestinal perforations, 4) malignancies, 5) anaphylaxis/hypersensitivity reactions, 6) demyelinating disorders, 7) stroke, 8) serious and/or medically significant bleeding events, and 9) serious and/or medically significant hepatic events. | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. | Posted | Number | percentage of participants | Up to Follow-up Week 32 |
|
|
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| Secondary | Percentage of Participants Who Required Dose Modifications or Discontinued Study Due to AEs | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. | Posted | Number | percentage of participants | Up to Week 24 |
|
|
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| Secondary | Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies | Reported is the percentage of participants positive for anti-tocilizumab antibodies in the confirmatory anti-tocilizumab antibody assay, which followed an initial anti-tocilizumab screen. Participants, who withdrew from the study | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure. | Posted | Number | percentage of participants | Baseline, Week 24, Follow-up Week 32 and Early Withdrawal |
|
|
|
| Secondary | Immunogenicity: Tocilizumab Levels | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure. | Posted | Mean | Standard Deviation | microgram/milliliter (mcg/mL) | Week 12, Week 24, Follow-up Week 32 and Early Withdrawal |
|
|
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| Secondary | Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels | A positive change from Week 1 indicates an increase in sIL-6R levels. | The FAS included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here n is the number of participants with evaluable data for this outcome measure. | Posted | Mean | Standard Deviation | nanograms/milliliter (ng/mL) | Week 1, Week 12, Week 24, Follow-up Week 32 and Early Withdrawal |
|
|
|
| 6 |
| 100 |
| 44 |
| 100 |
| Chest pain | General disorders | MedDRA (18.1) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
|
| Adnexal torsion | Reproductive system and breast disorders | MedDRA (18.1) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
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| Haematoma | Vascular disorders | MedDRA (18.1) | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA (18.1) | Systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
|
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| Title | Measurements |
|---|
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| SJC at Baseline |
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| SJC Change from Baseline at Week 24 |
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| HAS at Baseline |
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| HAS at Week 24 |
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| Follow-up Visit Week 32 |
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| Early Withdrawal |
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| Follow-up Week 32 |
|
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| Early withdrawal |
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| Change from Week 1 at Week 24 |
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| Change from Week 1 at Follow-up at Week 32 |
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| Change from Week 1 at Early withdrawal |
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