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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-019912-18 | EudraCT Number |
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This randomized, parallel-group, placebo-controlled, multicenter study will evaluate the reduction in disease activity and the safety of tocilizumab (RoActemra/Actemra) in combination with traditional disease-modifying anti-rheumatic drugs (DMARDs) in patients with active, moderate to severe rheumatoid arthritis. In the double-blind part of the study, patients will be randomized to receive either 162 mg tocilizumab or placebo subcutaneously every 2 weeks for 24 weeks using a pre-filled syringe. In the open-label part of the study, patients will be randomized to receive 162 mg tocilizumab subcutaneously every 2 weeks from Week 24 to Week 96 using a pre-filled syringe or an auto-injector.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tocilizumab 162 mg sc | Experimental | Patients will receive tocilizumab 162 mg subcutaneously (sc) every 2 weeks for 24 weeks. |
|
| Placebo sc | Placebo Comparator | Patients will receive placebo subcutaneously (sc) every 2 weeks for 24 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tocilizumab 162 mg | Drug | Tocilizumab will be supplied in a ready-to-use, single-use, pre-filled syringe. Patients and/or caregivers will be trained to administer the injection. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Patients With an American College of Rheumatology 20 (ACR20) Response at Week 24 | A patient had an ACR20 response if there was at least a 20% improvement, ie, reduction from baseline, in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, left end=no disease activity [symptom-free and no arthritis symptoms], right end=maximum disease activity; patient assessment of pain in previous 24 hours on a VAS (left end=no pain and right end=unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and acute-phase reactant (either C-reactive protein or erythrocyte sedimentation rate). | Baseline to Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Patients With ACR50 and ACR70 Responses at Week 24 | A patient had an ACR50 response if there was at least a 50% improvement in the ACR scores. A patient had an ACR70 response if there was at least a 70% improvement in the ACR scores. | Baseline to Week 24 |
| Time to Onset of ACR20, ACR50, and ACR70 Responses |
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Inclusion Criteria:
Exclusion Criteria:
Other inclusion and exclusion criteria applied to the study.
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peoria | Arizona | 85381 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24942540 | Derived | Kivitz A, Olech E, Borofsky M, Zazueta BM, Navarro-Sarabia F, Radominski SC, Merrill JT, Rowell L, Nasmyth-Miller C, Bao M, Wright S, Pope JE. Subcutaneous tocilizumab versus placebo in combination with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2014 Nov;66(11):1653-61. doi: 10.1002/acr.22384. |
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Of the 656 patients randomized into the study (437 to the tocilizumab arm and 219 to the placebo arm), 438 patients received tocilizumab as their first dose and 218 received placebo as their first dose because of a dose administration error with 1 patient.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tocilizumab 162 mg sc - Double-blind Treatment Period | Patients received tocilizumab 162 mg subcutaneously (sc) every 2 weeks for 24 weeks. |
| FG001 | Placebo sc - Double-blind Treatment Period |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Double-blind Treatment Period |
|
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|
| Placebo | Drug | Placebo will be supplied in a ready-to-use, single-use, pre-filled syringe. Patients and/or caregivers will be trained to administer the injection. |
|
Time to first ACR response was calculated as the number of days between the date of the first ACR response minus the date of the first dose of study drug. Median days are reported. |
| Baseline to Week 24 |
| Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 24 | Joints (28 joints) will be assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation on physical examination. | Baseline to Week 24 |
| Change From Baseline in C-reactive Protein at Week 24 | Baseline to Week 24 |
| Change From Baseline in Erythrocyte Sedimentation Rate at Week 24 | Baseline to Week 24 |
| Change From Baseline in the Patient's and the Physician's Global Assessment of Disease Activity Visual Analog (VAS) Score | Patients and physicians assessed the patient's disease activity in the previous 24 hours on a 100 mm visual analog scale, where the extreme left end of the line represented "no disease activity" (symptom-free and no arthritis symptoms) and the extreme right end represented "maximum disease activity". Scores ranged from 0 to 100 with a higher score indicating more disease activity. A negative change score indicated less disease activity. | Baseline to Week 24 |
| Change From Baseline in the Patient's Pain Visual Analog Score | Patients assessed their pain in the previous 24 hours on a visual analog scale, where the extreme left end of the line represented "no pain" and the extreme right end represented "unbearable pain". Scores ranged from 0 to 100 with a higher score indicating more pain. A negative change score indicated less pain. | Baseline to Week 24 |
| Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 | The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Patients completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement. | Baseline to Week 24 |
| Percentage of Patients With an Improvement of ≥ 0.3 Units From Baseline in the HAQ-DI Score at Week 24 | The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Patients completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement. | Baseline to Week 24 |
| Change From Baseline in Disease Activity Score 28 (DAS28) at Week 24 | The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. | Baseline to Week 24 |
| Percentage of Patients With a DAS28 Score ≤ 3.2 (DAS28 Low Disease Activity) at Week 24 | The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. | Baseline to Week 24 |
| Percentage of Patients With a DAS28 Score < 2.6 (DAS28 Remission) at Week 24 | The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. | Week 24 |
| Percentage of Patients With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24 | Change of the Disease Activity Score 28 score from baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of < -1.2 was a good response, < -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score > 3.2 to ≤ 5.1, a change from baseline of < -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score > 5.1, a change from baseline < -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores > 3.2. | Baseline to Week 24 |
| Change From Baseline in the Van Der Heijde Modified Sharp Radiographic Score at Week 24 | The degree of joint damage was assessed using the van der Heijde modified total Sharp score (mTSS). The methodology quantifies the extent of bone erosions for 44 joints and joint space narrowing (JSN) for 42 joints, with higher scores representing greater damage. The independent read of X-ray images was performed by 2 primary readers. In case of discrepancy between the 2 primary readers, an adjudicator was involved. The mTSS can range from 0 to 448 with a higher score indicating more joint damage. A negative change score indicates improvement. | Baseline to Week 24 |
| Change From Baseline in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Week 24 | The SF-36 Health Survey uses patient-reported symptoms on 8 subscales to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100 with a higher score indicating better HRQoL. A positive change score indicates an improvement in HRQoL. | Baseline to Week 24 |
| Change From Baseline in Hemoglobin at Week 24 | Baseline to Week 24 |
| Scottsdale |
| Arizona |
| 85258 |
| United States |
| Tucson | Arizona | 85723 | United States |
| Tucson | Arizona | 85724 | United States |
| Fullerton | California | 92835 | United States |
| San Diego | California | 92108 | United States |
| San Leandro | California | 94578 | United States |
| West Hills | California | 91307 | United States |
| Trumbull | Connecticut | 06611 | United States |
| Boca Raton | Florida | 33486 | United States |
| Jupiter | Florida | 33458 | United States |
| Ormond Beach | Florida | 32174 | United States |
| Sarasota | Florida | 34292 | United States |
| Gainesville | Georgia | 30501 | United States |
| Idaho Falls | Idaho | 83404 | United States |
| Meridan | Idaho | 83642 | United States |
| Springfield | Illinois | 62704 | United States |
| Vernon Hills | Illinois | 60061 | United States |
| Crofton | Maryland | 21114 | United States |
| Hagerstown | Maryland | 21740 | United States |
| Wheaton | Maryland | 20902 | United States |
| Flowood | Mississippi | 39232 | United States |
| Jackson | Mississippi | 39202 | United States |
| St Louis | Missouri | 63128 | United States |
| St Louis | Missouri | 63141 | United States |
| Lincoln | Nebraska | 68516 | United States |
| Brooklyn | New York | 11201 | United States |
| Belmont | North Carolina | 28012 | United States |
| Charlotte | North Carolina | 28204 | United States |
| Charlotte | North Carolina | 28207 | United States |
| Charlotte | North Carolina | 28211 | United States |
| Oklahoma City | Oklahoma | 73104 | United States |
| Allentown | Pennsylvania | 18103 | United States |
| Bethlehem | Pennsylvania | 18015 | United States |
| Duncansville | Pennsylvania | 16635 | United States |
| Wexford | Pennsylvania | 15090 | United States |
| Wyomissing | Pennsylvania | 19610 | United States |
| Memphis | Tennessee | 38104 | United States |
| Dallas | Texas | 75246 | United States |
| Fort Worth | Texas | 76107 | United States |
| Houston | Texas | 77034 | United States |
| Houston | Texas | 77459 | United States |
| San Antonio | Texas | 78232 | United States |
| Tacoma | Washington | 98405 | United States |
| Buenos Aires | C1015ABO | Argentina |
| Córdoba | 5000 | Argentina |
| San Miguel de Tucumán | 4000 | Argentina |
| Cairns | 4870 | Australia |
| Kogarah | 2217 | Australia |
| Curitiba | 80060-240 | Brazil |
| Goiânia | 74043-011 | Brazil |
| Juiz de Fora | 36010-570 | Brazil |
| Porto Alegre | 90610-000 | Brazil |
| Porto Alegre | 91350-200 | Brazil |
| Rio de Janeiro | 22271-100 | Brazil |
| Salvador | 40050-410 | Brazil |
| São Paulo | 04026-000 | Brazil |
| São Paulo | 04266-010 | Brazil |
| São Paulo | 05437-010 | Brazil |
| São Paulo | 1244030 | Brazil |
| São Paulo | 5403900 | Brazil |
| Vitória | 29055-450 | Brazil |
| Plovdiv | 4002 | Bulgaria |
| Plovdiv | 4003 | Bulgaria |
| Sofia | 1612 | Bulgaria |
| Sofia | 2233 | Bulgaria |
| Varna | 9010 | Bulgaria |
| Calgary | Alberta | T2N 2T9 | Canada |
| Winnipeg | Manitoba | R3A 1M3 | Canada |
| Winnipeg | Manitoba | R3N 0K6 | Canada |
| London | Ontario | N6A 4V2 | Canada |
| Ottawa | Ontario | K1H 1A2 | Canada |
| Pointe-Claire | Quebec | H9R 3J1 | Canada |
| Bogotá | Colombia |
| Chia-cundinamarca | Colombia |
| MedellÃn | Colombia |
| Athens | 11527 | Greece |
| Athens | 15121 | Greece |
| Thessaloniki | 54636 | Greece |
| Guatemala City | 01010 | Guatemala |
| Guatemala City | 01013 | Guatemala |
| Guatemala City | 01015 | Guatemala |
| Budapest | 1036 | Hungary |
| Debrecen | 4004 | Hungary |
| Ashkelon | 78306 | Israel |
| Beersheba | 84101 | Israel |
| Haifa | 31048 | Israel |
| Haifa | 31096 | Israel |
| Ramat Gan | 52621 | Israel |
| Rishon LeZiyyon | Israel |
| Tel Aviv | 64239 | Israel |
| Batu Caves | 68100 | Malaysia |
| Kota Kinabalu | 88586 | Malaysia |
| Kuala Lumpur | 50603 | Malaysia |
| Chihuahua City | 31000 | Mexico |
| Culiacán | 80000 | Mexico |
| Guadalajara | 44158 | Mexico |
| León | 37320 | Mexico |
| Mexicali | 21100 | Mexico |
| Mérida | 97000 | Mexico |
| México | 44620 | Mexico |
| Morelia | 58070 | Mexico |
| Obregón | 85000 | Mexico |
| Querétaro | 76000 | Mexico |
| Querétaro | 76178 | Mexico |
| Otahuhu | 1006 | New Zealand |
| Panama City | 32400 | Panama |
| Cebu | 6000 | Philippines |
| Davao City | 8006 | Philippines |
| Manila | 1780 | Philippines |
| Bytom | 41902 | Poland |
| Działdowo | 13-200 | Poland |
| Elblag | 82-300 | Poland |
| Kościan | 64-000 | Poland |
| Krakow | 31-121 | Poland |
| Torun | 87-100 | Poland |
| Warsaw | 02-653 | Poland |
| Kemerovo | 650099 | Russia |
| Moscow | 115522 | Russia |
| Moscow | 117049 | Russia |
| Moscow | 129327 | Russia |
| Novosibirsk | 630099 | Russia |
| Petrozavodsk | 185019 | Russia |
| Ryazan | 390026 | Russia |
| Saint Petersburg | 190068 | Russia |
| Saint Petersburg | 197022 | Russia |
| Saint Petersburg | 197341 | Russia |
| Ufa | 450005 | Russia |
| Voronezh | 394066 | Russia |
| Durban | 4013 | South Africa |
| Pinelands | 7405 | South Africa |
| Pretoria | 0002 | South Africa |
| A Coruña | 15006 | Spain |
| Oviedo | 33006 | Spain |
| Seville | 41009 | Spain |
| Fribourg | 1708 | Switzerland |
| Geneva | 1211 | Switzerland |
| Lausanne | 1011 | Switzerland |
| Zurich | 8063 | Switzerland |
| Bangkok | 10400 | Thailand |
| Bangkok | 10700 | Thailand |
Patients received placebo sc every 2 weeks for 24 weeks.
| FG002 | Tocilizumab Pre-filled Syringe - Open-label Extension Period | Patients received tocilizumab 162 mg sc via a pre-filled syringe every 2 weeks for 72 weeks. |
| FG003 | Tocilizumab Auto-injector - Open-label Extension Period | Patients received tocilizumab 162 mg sc via auto-injector every 2 weeks for 72 weeks. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Open-label Extension Period |
|
Baseline Characteristics are reported for the safety population which included all patients who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. One patient who received tocilizumab had no post-baseline safety data and was excluded from the safety population.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Tocilizumab 162 mg sc | Patients received tocilizumab 162 mg subcutaneously (sc) every 2 weeks for 24 weeks. |
| BG001 | Placebo sc | Patients received placebo subcutaneously (sc) every 2 weeks for 24 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| 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 Patients With an American College of Rheumatology 20 (ACR20) Response at Week 24 | A patient had an ACR20 response if there was at least a 20% improvement, ie, reduction from baseline, in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, left end=no disease activity [symptom-free and no arthritis symptoms], right end=maximum disease activity; patient assessment of pain in previous 24 hours on a VAS (left end=no pain and right end=unbearable pain); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and acute-phase reactant (either C-reactive protein or erythrocyte sedimentation rate). | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Number | 95% Confidence Interval | Percentage of patients | Baseline to Week 24 |
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| Secondary | Percentage of Patients With ACR50 and ACR70 Responses at Week 24 | A patient had an ACR50 response if there was at least a 50% improvement in the ACR scores. A patient had an ACR70 response if there was at least a 70% improvement in the ACR scores. | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Number | 95% Confidence Interval | Percentage of patients | Baseline to Week 24 |
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| Secondary | Time to Onset of ACR20, ACR50, and ACR70 Responses | Time to first ACR response was calculated as the number of days between the date of the first ACR response minus the date of the first dose of study drug. Median days are reported. | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Median | 95% Confidence Interval | Days | Baseline to Week 24 |
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| Secondary | Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 24 | Joints (28 joints) will be assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation on physical examination. | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Mean | Standard Deviation | Joint count | Baseline to Week 24 |
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| Secondary | Change From Baseline in C-reactive Protein at Week 24 | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Mean | Standard Deviation | mg/dL | Baseline to Week 24 |
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| Secondary | Change From Baseline in Erythrocyte Sedimentation Rate at Week 24 | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Mean | Standard Deviation | mm/hr | Baseline to Week 24 |
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| Secondary | Change From Baseline in the Patient's and the Physician's Global Assessment of Disease Activity Visual Analog (VAS) Score | Patients and physicians assessed the patient's disease activity in the previous 24 hours on a 100 mm visual analog scale, where the extreme left end of the line represented "no disease activity" (symptom-free and no arthritis symptoms) and the extreme right end represented "maximum disease activity". Scores ranged from 0 to 100 with a higher score indicating more disease activity. A negative change score indicated less disease activity. | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Mean | Standard Deviation | Units on a scale | Baseline to Week 24 |
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| Secondary | Change From Baseline in the Patient's Pain Visual Analog Score | Patients assessed their pain in the previous 24 hours on a visual analog scale, where the extreme left end of the line represented "no pain" and the extreme right end represented "unbearable pain". Scores ranged from 0 to 100 with a higher score indicating more pain. A negative change score indicated less pain. | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Mean | Standard Deviation | Units on a scale | Baseline to Week 24 |
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| Secondary | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 | The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Patients completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement. | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Mean | Standard Deviation | Units on a scale | Baseline to Week 24 |
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| Secondary | Percentage of Patients With an Improvement of ≥ 0.3 Units From Baseline in the HAQ-DI Score at Week 24 | The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Patients completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement. | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Number | 95% Confidence Interval | Percentage of patients | Baseline to Week 24 |
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| Secondary | Change From Baseline in Disease Activity Score 28 (DAS28) at Week 24 | The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Mean | Standard Deviation | Units on a scale | Baseline to Week 24 |
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| Secondary | Percentage of Patients With a DAS28 Score ≤ 3.2 (DAS28 Low Disease Activity) at Week 24 | The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Number | 95% Confidence Interval | Percentage of patients | Baseline to Week 24 |
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| Secondary | Percentage of Patients With a DAS28 Score < 2.6 (DAS28 Remission) at Week 24 | The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Number | 95% Confidence Interval | Percentage of patients | Week 24 |
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| Secondary | Percentage of Patients With Good, Moderate, or no European League Against Rheumatism (EULAR) Responses at Week 24 | Change of the Disease Activity Score 28 score from baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of < -1.2 was a good response, < -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score > 3.2 to ≤ 5.1, a change from baseline of < -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score > 5.1, a change from baseline < -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores > 3.2. | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Number | Percentage of patients | Baseline to Week 24 |
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| Secondary | Change From Baseline in the Van Der Heijde Modified Sharp Radiographic Score at Week 24 | The degree of joint damage was assessed using the van der Heijde modified total Sharp score (mTSS). The methodology quantifies the extent of bone erosions for 44 joints and joint space narrowing (JSN) for 42 joints, with higher scores representing greater damage. The independent read of X-ray images was performed by 2 primary readers. In case of discrepancy between the 2 primary readers, an adjudicator was involved. The mTSS can range from 0 to 448 with a higher score indicating more joint damage. A negative change score indicates improvement. | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Mean | Standard Deviation | Units on a scale | Baseline to Week 24 |
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| Secondary | Change From Baseline in the Physical and Mental Component Scores of the Short Form 36 (SF-36) Health Survey at Week 24 | The SF-36 Health Survey uses patient-reported symptoms on 8 subscales to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role-Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role-Emotional, and Mental Health. Each score was scaled from 0 to 100 with a higher score indicating better HRQoL. A positive change score indicates an improvement in HRQoL. | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Mean | Standard Deviation | Units on a scale | Baseline to Week 24 |
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| Secondary | Change From Baseline in Hemoglobin at Week 24 | Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were assigned to the ITT population as randomized, irrespective of the treatment actually received. Only patients with available data were included in the analysis. | Posted | Mean | Standard Deviation | g/L | Baseline to Week 24 |
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Not provided
Safety population: All patients who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. One patient who received tocilizumab had no post-baseline safety data and was excluded from the safety population.
Due to the study design, some participants received tocilizumab throughout the study, others not.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tocilizumab Pre-filled Syringe | Patients received tocilizumab 162 mg sc via a pre-filled syringe every 2 weeks for 24 weeks. In addition, this reporting group includes participants re-randomized at Week 24 to tocilizumab 162 mg sc via a pre-filled syringe every 2 weeks for 72 weeks (Weeks 25-96). | 36 | 437 | 212 | 437 | ||
| EG001 | Placebo Pre-filled Syringe | Patients received placebo subcutaneously (sc) via a pre-filled syringe every 2 weeks for 24 weeks. | 8 | 218 | 65 | 218 | ||
| EG002 | Tocilizumab Pre-filled Syringe to Tocilizumab Auto-injector | Patients received tocilizumab 162 mg sc via a pre-filled syringe every 2 weeks for 24 weeks followed by tocilizumab162 mg sc via an autoinjector every 2 weeks for 72 weeks. | 17 | 168 | 89 | 168 | ||
| EG003 | Placebo Pre-filled Syringe to Tocilizumab Pre-filled Syringe | Patients received placebo sc via a pre-filled syringe every 2 weeks for 24 weeks followed by tocilizumab162 mg sc via a pre-filled syringe every 2 weeks for 72 weeks. | 2 | 61 | 35 | 61 | ||
| EG004 | Placebo Pre-filled Syringe to Tocilizumab Autoinjector | Patients received placebo sc via a pre-filled syringe every 2 weeks for 24 weeks followed by tocilizumab162 mg sc via an autoinjector every 2 weeks for 72 weeks. | 0 | 59 | 33 | 59 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Abscess | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Arthritis bacterial | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Bronchopneumonia | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Coccidioidomycosis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Postoperative wound infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Pulmonary tuberculosis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Spinal column stenosis | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Synovial cyst | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Adenocarcinoma pancreas | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment |
| |
| Renal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment |
| |
| Grand mal convulsion | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Lumbar radiculopathy | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Ovarian cyst | Reproductive system and breast disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Cervical vertebral fracture | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
| |
| Bipolar disorder | Psychiatric disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Joint abscess | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Ludwig angina | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Abdominal adhesions | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Diverticulum intestinal | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Haemorrhagic inguinal hernia | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Myelodysplastic syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment |
| |
| Ovarian epithelial cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment |
| |
| Rectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment |
| |
| Schwannoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.0) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Endometrial hypertrophy | Reproductive system and breast disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Ovarian cyst torsion | Reproductive system and breast disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Calculus ureteric | Renal and urinary disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Pyoderma gangrenosum | Skin and subcutaneous tissue disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Adrenocortical insufficiency | Endocrine disorders | MedDRA (15.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | MedDRA (15.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (15.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Dyslipidaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
| |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | 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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800 821-8590 |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C502936 | tocilizumab |
Not provided
Not provided
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Patients received placebo subcutaneously (sc) every 2 weeks for 24 weeks.
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Patients received placebo subcutaneously (sc) every 2 weeks for 24 weeks.
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