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This 3 arm randomized open label study will evaluate the safety, tolerability and efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis, who have had inadequate response to or are unable to tolerate DMARDs. The protocol incorporates risk mitigation strategies developed in partnership with the FDA to manage known and potential risks associated with the treatment of tocilizumab. Patients will be randomized to receive tocilizumab either 4 mg/kg intravenous (iv) or 8 mg/kg iv with concomitant non-biologic DMARDs, or 8 mg/kg iv without concomitant non-biologic DMARDs, every 4 weeks, for a total of 6 infusions. The anticipated time on study treatment is 3-12 months, and the target sample size is 500-1000 individuals.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tocilizumab 8 mg/kg Monotherapy | Experimental | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion. |
|
| Tocilizumab 4 mg/kg + DMARD | Experimental | Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion. |
|
| Tocilizumab 8 mg/kg + DMARD | Experimental | Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tocilizumab [RoActemra/Actemra] | Drug | 8 mg/kg intravenous every 4 weeks for 24 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Experiencing at Least One Serious Adverse Event (SAE) During the 24 Week Treatment Period | An SAE was any adverse event that at any dose fulfilled at least one of the following criteria:
| 24 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Experiencing Serious Adverse Events of Special Interest | Serious Adverse Events of Special interest include:
| 24 Weeks |
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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 |
|---|---|---|---|---|---|---|
| Anniston | Alabama | 36207 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22972745 | Derived | Weinblatt ME, Kremer J, Cush J, Rigby W, Teng LL, Devenport J, Singh N, Lepley D, Genovese MC. Tocilizumab as monotherapy or in combination with nonbiologic disease-modifying antirheumatic drugs: twenty-four-week results of an open-label, clinical practice study. Arthritis Care Res (Hoboken). 2013 Mar;65(3):362-71. doi: 10.1002/acr.21847. |
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1129 patients were screened for the study. Of these 1129 patients, 886 patients were enrolled and 243 patients were screen failures.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tocilizumab 8 mg/kg Monotherapy | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| 24 Week Treatment Period |
|
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| tocilizumab [RoActemra/Actemra] | Drug | 4 mg/kg every 4 weeks for 24 weeks |
|
| Nonbiologic DMARDs of investigator's choice | Drug | Nonbiologic disease-modifying antirheumatic drugs (DMARDs) As prescribed |
|
| Percentage of Participants Experiencing Non-serious Adverse Events of Special Interest | Non-serious adverse Events of Special interest include:
| 24 Weeks |
| Percentage of Participants Achieving Clinical Remission at Weeks 8, 16, and 24 | Clinical Remission is defined as a Disease Activity Score 28 [DAS28] < 2.6. The DAS28 is a combined index for measuring disease activity in RA. The index includes tender joint count (TJC) -28 joints and swollen joint count (SJC)-28 joints, acute phase response (CRP) and general health status. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. | Weeks 8,16,24 |
| Change From Baseline in DAS28 Score at Weeks 8, 16 and 24 | The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes tender joint count (TJC) -28 joints and swollen joint count (SJC)-28 joints, acute phase response C-reactive protein (CRP) and general health status. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of < 2.6 represents clinical remission, a score of ≤ 3.2 represents low disease activity, and a score of > 5.1 represents high disease activity. The Change from Baseline to Weeks 8, 16 and 24 is reported. | Baseline, Weeks 8,16,24 |
| Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24 | The ACR response rates ACR20, ACR50, and ACR70 are defined as ≥20%, ≥50%, and ≥70% improvement from baseline, respectively, in:
| Baseline, Weeks 8,16,24 |
| Percentage of Participants With Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Week 8 | Dosage could be increased from 4 mg/kg Tocilizumab to 8 mg/kg due to failure to achieve 20% improvement from baseline in swollen and tender joint counts. | Baseline, Week 8 |
| Number of Participants Having Their Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Weeks 12, 16, and 20 | Dosage of Tocilizumab 4 mg/kg could be increased to 8 mg/kg at the discretion of the investigator based on assessment of the patient's benefit-risk after Week 12. | Weeks 12,16, 20 |
| Change From Baseline in Routine Assessment Patient Index Data (RAPID3) Score at Weeks 8, 16, and 24 | The RAPID3 is a combined index derived from the Multidimensional Health Assessment Questionnaire that includes physical function score, pain Visual Analog Scale (VAS), and global assessment of disease activity VAS. The total RAPID3 score ranges from 0 to 10 where higher scores represent worse outcomes. A negative change from baseline indicates improvement. | Baseline, Weeks 8,16,24 |
| Change From Baseline in Fatigue Visual Analogue Scale (VAS) at Weeks 8, 16, and 24 | The fatigue VAS is a single-item, patient-reported outcome that measures the severity of the fatigue over the past week. Patients rate their fatigue on a scale of 0 (fatigue is no problem) to 100 (fatigue is a major problem). Higher scores represent higher disease activity and a negative change from baseline indicates improvement. | Baseline, Weeks 8,16,24 |
| Birmingham |
| Alabama |
| 35205 |
| United States |
| Birmingham | Alabama | 35294 | United States |
| Huntsville | Alabama | 35801 | United States |
| Mobile | Alabama | 36608 | United States |
| Montgomery | Alabama | 36111 | United States |
| Tuscaloosa | Alabama | 35406 | United States |
| Hot Springs | Arizona | 71913 | United States |
| Paradise Valley | Arizona | 85253 | United States |
| Peoria | Arizona | 85381 | United States |
| Scottsdale | Arizona | 85251 | United States |
| Scottsdale | Arizona | 85258 | United States |
| Tucson | Arizona | 85704 | United States |
| Fayetteville | Arkansas | 27203 | United States |
| Fort Smith | Arkansas | 72903 | United States |
| Jonesboro | Arkansas | 72401 | United States |
| Little Rock | Arkansas | 72205 | United States |
| Covina | California | 91723 | United States |
| Escondido | California | 92025 | United States |
| Fullerton | California | 92835 | United States |
| Huntington Beach | California | 92646 | United States |
| La Jolla | California | 92037 | United States |
| Lakewood | California | 90712 | United States |
| Long Beach | California | 90808 | United States |
| Los Angeles | California | 90048 | United States |
| Murrieta | California | 92563 | United States |
| Newport Beach | California | 92663 | United States |
| Pasadena | California | 91107 | United States |
| Sacramento | California | 95825 | United States |
| San Diego | California | 92108 | United States |
| San Leandro | California | 94578 | United States |
| Santa Barbara | California | 93108 | United States |
| Santa Maria | California | 93454 | United States |
| Sherman Oaks | California | 91423 | United States |
| Van Nuys | California | 91405 | United States |
| Victorville | California | 92295 | United States |
| Westlake Village | California | 91361 | United States |
| Whittier | California | 90606 | United States |
| Colorado Springs | Colorado | 80910 | United States |
| Denver | Colorado | 80230 | United States |
| Bridgeport | Connecticut | 06606 | United States |
| Danbury | Connecticut | 06810 | United States |
| Hamden | Connecticut | 06518 | United States |
| Trumbull | Connecticut | 06611 | United States |
| Lewes | Delaware | 19958 | United States |
| Aventura | Florida | 33180 | United States |
| Boca Raton | Florida | 33486 | United States |
| Clearwater | Florida | 33761 | United States |
| Dunedin | Florida | 34698 | United States |
| Fort Lauderdale | Florida | 33334 | United States |
| Gainesville | Florida | 30501 | United States |
| Gainesville | Florida | 32608 | United States |
| Jacksonville | Florida | 32209 | United States |
| Lake Mary | Florida | 32746 | United States |
| Melbourne | Florida | 32901 | United States |
| Miami | Florida | 33126 | United States |
| Miami | Florida | 33133 | United States |
| Naples | Florida | 34102 | United States |
| Ocala | Florida | 34474 | United States |
| Orlando | Florida | 32806 | United States |
| Palm Harbor | Florida | 34684 | United States |
| Sarasota | Florida | 34239 | United States |
| South Miami | Florida | 33143 | United States |
| St. Petersburg | Florida | 33710 | United States |
| Tampa | Florida | 33614 | United States |
| Tampa | Florida | 33618 | United States |
| Atlanta | Georgia | 30342 | United States |
| Gainesville | Georgia | 30501 | United States |
| Boise | Idaho | 83702 | United States |
| Idaho Falls | Idaho | 83404 | United States |
| Nampa | Idaho | 83686 | United States |
| Chicago | Illinois | 60616 | United States |
| Maywood | Illinois | 60153 | United States |
| Moline | Illinois | 61265 | United States |
| Morton Grove | Illinois | 60053 | United States |
| Peoria | Illinois | 61602 | United States |
| Schaumburg | Illinois | 60195 | United States |
| Springfield | Illinois | 62704 | United States |
| Vernon Hills | Illinois | 60061 | United States |
| Evansville | Indiana | 47714 | United States |
| Fort Wayne | Indiana | 46804 | United States |
| South Bend | Indiana | 46601 | United States |
| Cedar Rapids | Iowa | 52401 | United States |
| Lees Summit | Kansas | 64086 | United States |
| Wichita | Kansas | 67208 | United States |
| Lexington | Kentucky | 40515 | United States |
| Baton Rouge | Louisiana | 70808 | United States |
| Baton Rouge | Louisiana | 70810 | United States |
| Monroe | Louisiana | 71203 | United States |
| New Orleans | Louisiana | 70121 | United States |
| Columbia | Maryland | 21045 | United States |
| Ellicott City | Maryland | 21042 | United States |
| Frederick | Maryland | 21702 | United States |
| Wheaton | Maryland | 20902 | United States |
| Boston | Massachusetts | 02115 | United States |
| Fall River | Massachusetts | 02720 | United States |
| Pascagoula | Massachusetts | 39581 | United States |
| Peabody | Massachusetts | 01960 | United States |
| Plymouth | Massachusetts | 02360 | United States |
| Worcester | Massachusetts | 01605 | United States |
| Worcester | Massachusetts | 01610 | United States |
| Battle Creek | Michigan | 49015 | United States |
| Kalamazoo | Michigan | 49048 | United States |
| Lansing | Michigan | 48910 | United States |
| Petoskey | Michigan | 49770 | United States |
| Saint Clair Shores | Michigan | 48080 | United States |
| Duluth | Minnesota | 55805 | United States |
| Eagan | Minnesota | 55121 | United States |
| Edina | Minnesota | 55435 | United States |
| Saint Louis Park | Minnesota | 55426 | United States |
| Flowood | Mississippi | 39232 | United States |
| Hattiesburg | Mississippi | 39402 | United States |
| Jackson | Mississippi | 39202 | United States |
| Tupelo | Mississippi | 38802 | United States |
| Florissant | Missouri | 63031 | United States |
| St Louis | Missouri | 63110 | United States |
| St Louis | Missouri | 63117 | United States |
| St Louis | Missouri | 63128 | United States |
| St Louis | Missouri | 63141 | United States |
| Kalispell | Montana | 59901 | United States |
| Grand Island | Nebraska | 68803 | United States |
| Lincoln | Nebraska | 68516 | United States |
| Reno | Nevada | 89502 | United States |
| Dover | New Hampshire | 03820 | United States |
| Lebanon | New Hampshire | 03756 | United States |
| Clifton | New Jersey | 07012 | United States |
| Haddon Heights | New Jersey | 08035 | United States |
| Manalapan | New Jersey | 07726 | United States |
| Morristown | New Jersey | 07962 | United States |
| New Brunswick | New Jersey | 08903 | United States |
| Trenton | New Jersey | 08360 | United States |
| Voorhees Township | New Jersey | 08043 | United States |
| Las Cruces | New Mexico | 88011 | United States |
| Albany | New York | 12206 | United States |
| Binghamton | New York | 13905 | United States |
| Brooklyn | New York | 11201 | United States |
| Cooperstown | New York | 13326 | United States |
| Hewlett | New York | 11557 | United States |
| Lake Success | New York | 11042 | United States |
| New York | New York | 10016 | United States |
| Olean | New York | 14760 | United States |
| Orchard Park | New York | 14127 | United States |
| Plainview | New York | 11803 | United States |
| Rochester | New York | 14618 | United States |
| Roslyn | New York | 11576 | United States |
| Smithtown | New York | 11787 | United States |
| Syracuse | New York | 13210 | United States |
| Utica | New York | 13504 | United States |
| Asheville | North Carolina | 28803 | United States |
| Belmont | North Carolina | 28012 | United States |
| Charlotte | North Carolina | 28204 | United States |
| Charlotte | North Carolina | 28207 | United States |
| Charlotte | North Carolina | 28210 | United States |
| Durham | North Carolina | 27704 | United States |
| Greenville | North Carolina | 27834 | United States |
| Raleigh | North Carolina | 27609 | United States |
| Rock Hill | North Carolina | 29732 | United States |
| Wilmington | North Carolina | 28401 | United States |
| Bismarck | North Dakota | 58501 | United States |
| Akron | Ohio | 44333 | United States |
| Cincinnati | Ohio | 45219 | United States |
| Cincinnati | Ohio | 45255 | United States |
| Columbus | Ohio | 43210 | United States |
| Columbus | Ohio | 43215 | United States |
| Dayton | Ohio | 45402 | United States |
| Gallipolis | Ohio | 45631 | United States |
| Mayfield | Ohio | 44143 | United States |
| Middleburg Heights | Ohio | 44130 | United States |
| Perryburg | Ohio | 43551 | United States |
| Zanesville | Ohio | 43701 | United States |
| Oklahoma City | Oklahoma | 73103 | United States |
| Oklahoma City | Oklahoma | 73109 | United States |
| Tulsa | Oklahoma | 74135 | United States |
| Lake Oswego | Oregon | 97035 | United States |
| Bethlehem | Pennsylvania | 18015 | United States |
| Camp Hill | Pennsylvania | 17011 | United States |
| Duncansville | Pennsylvania | 16635 | United States |
| Lebanon | Pennsylvania | 17042 | United States |
| Philadelphia | Pennsylvania | 19141 | United States |
| Philadelphia | Pennsylvania | 19152 | United States |
| Pottstown | Pennsylvania | 19464 | United States |
| West Reading | Pennsylvania | 19611 | United States |
| Wexford | Pennsylvania | 15090 | United States |
| Willow Grove | Pennsylvania | 19090 | United States |
| Charleston | South Carolina | 29406 | United States |
| Columbia | South Carolina | 29204 | United States |
| Hickory Grove | South Carolina | 28602 | United States |
| Myrtle Beach | South Carolina | 29572 | United States |
| Hendersonville | Tennessee | 37073 | United States |
| Hixson | Tennessee | 37343 | United States |
| Jackson | Tennessee | 38305 | United States |
| Knoxville | Tennessee | 37909 | United States |
| Nashville | Tennessee | 37027 | United States |
| Amarillo | Texas | 79106 | United States |
| Amarillo | Texas | 79124 | United States |
| Austin | Texas | 78705 | United States |
| Austin | Texas | 78749 | United States |
| Carrollton | Texas | 75007 | United States |
| Dallas | Texas | 75231-4406 | United States |
| Dallas | Texas | 75231 | United States |
| Dallas | Texas | 75246 | United States |
| Fort Worth | Texas | 76107 | United States |
| Houston | Texas | 77074 | United States |
| Houston | Texas | 77090 | United States |
| Lubbock | Texas | 79424 | United States |
| Mesquite | Texas | 75150 | United States |
| Nassau Bay | Texas | 77058 | United States |
| San Antonio | Texas | 78217 | United States |
| San Antonio | Texas | 78229 | United States |
| San Antonio | Texas | 78258 | United States |
| Tyler | Texas | 75701 | United States |
| Waco | Texas | 76708 | United States |
| Burlington | Vermont | 05401 | United States |
| Arlington | Virginia | 22205 | United States |
| Burke | Virginia | 22015 | United States |
| Richmond | Virginia | 23294 | United States |
| Virginia Beach | Virginia | 23454 | United States |
| Olympia | Washington | 98502 | United States |
| Spokane | Washington | 99204 | United States |
| Tacoma | Washington | 98405 | United States |
| Beckley | West Virginia | 25801 | United States |
| Clarksburg | West Virginia | 26301 | United States |
| Brookfield | Wisconsin | 53045 | United States |
| Franklin | Wisconsin | 53132 | United States |
| Glendale | Wisconsin | 53217 | United States |
| Milwaukee | Wisconsin | 53209 | United States |
| Onalaska | Wisconsin | 54605 | United States |
| Tocilizumab 4 mg/kg + DMARD |
Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. |
| FG002 | Tocilizumab 8 mg/kg + DMARD | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. |
| Intent-to-Treat (ITT) |
|
| Safety Set |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Long-term Extension Period |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Tocilizumab 8 mg/kg Monotherapy | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. |
| BG001 | Tocilizumab 4 mg/kg + DMARD | Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. |
| BG002 | Tocilizumab 8 mg/kg + DMARD | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. |
| BG003 | 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 | Baseline measures are based on the number of participants in the Safety Population who received at least one dose of study drug and who had at least one post baseline safety assessment. | Mean | Standard Deviation | years |
| ||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| 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 Experiencing at Least One Serious Adverse Event (SAE) During the 24 Week Treatment Period | An SAE was any adverse event that at any dose fulfilled at least one of the following criteria:
| Safety Population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy. | Posted | Number | Percentage of Participants | 24 Weeks |
|
|
| ||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Experiencing Serious Adverse Events of Special Interest | Serious Adverse Events of Special interest include:
| Safety Population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy. | Posted | Number | Percentage of Participants | 24 Weeks |
| ||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Experiencing Non-serious Adverse Events of Special Interest | Non-serious adverse Events of Special interest include:
| Safety Population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy. | Posted | Number | Percentage of Participants | 24 Weeks |
| ||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Achieving Clinical Remission at Weeks 8, 16, and 24 | Clinical Remission is defined as a Disease Activity Score 28 [DAS28] < 2.6. The DAS28 is a combined index for measuring disease activity in RA. The index includes tender joint count (TJC) -28 joints and swollen joint count (SJC)-28 joints, acute phase response (CRP) and general health status. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. | Intent-to-treat population includes participants who received at least one dose of study drug. Patients were included in the treatment group to which they were randomized or assigned, regardless of the treatment actually received. "n" in each of the categories is the number of participants with data available for analysis at the given time point. | Posted | Number | Percentage of Participants | Weeks 8,16,24 |
| ||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in DAS28 Score at Weeks 8, 16 and 24 | The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes tender joint count (TJC) -28 joints and swollen joint count (SJC)-28 joints, acute phase response C-reactive protein (CRP) and general health status. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of < 2.6 represents clinical remission, a score of ≤ 3.2 represents low disease activity, and a score of > 5.1 represents high disease activity. The Change from Baseline to Weeks 8, 16 and 24 is reported. | Intent-to-treat includes participants who received at least one dose of study drug. Patients were included in the treatment group to which they were randomized or assigned, regardless of the treatment actually received. "n" in each of the categories is the number of participants with data available for analysis at the given time point. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Weeks 8,16,24 |
| |||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24 | The ACR response rates ACR20, ACR50, and ACR70 are defined as ≥20%, ≥50%, and ≥70% improvement from baseline, respectively, in:
| Intent-to-treat population includes all participants who received at least one dose of study drug. Patients were included in the treatment group to which they were randomized or assigned, regardless of the treatment actually received. | Posted | Number | Percentage of Participants | Baseline, Weeks 8,16,24 |
| ||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Week 8 | Dosage could be increased from 4 mg/kg Tocilizumab to 8 mg/kg due to failure to achieve 20% improvement from baseline in swollen and tender joint counts. | Safety Population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy. | Posted | Number | Percentage of Participants | Baseline, Week 8 |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Having Their Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Weeks 12, 16, and 20 | Dosage of Tocilizumab 4 mg/kg could be increased to 8 mg/kg at the discretion of the investigator based on assessment of the patient's benefit-risk after Week 12. | Safety population includes participants who received at least one dose of study drug. "n" in each of the categories is the number of participants previously on 4mg/kg + DMARD and receiving a dose at the current visit. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. | Posted | Number | Participants | Weeks 12,16, 20 |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Routine Assessment Patient Index Data (RAPID3) Score at Weeks 8, 16, and 24 | The RAPID3 is a combined index derived from the Multidimensional Health Assessment Questionnaire that includes physical function score, pain Visual Analog Scale (VAS), and global assessment of disease activity VAS. The total RAPID3 score ranges from 0 to 10 where higher scores represent worse outcomes. A negative change from baseline indicates improvement. | Intent-to-treat population includes all participants who received at least 1 dose of study drug. Patients were included in the treatment group to which they were randomized or assigned, regardless of the treatment actually received. "n" in each of the categories is the number of participants with data available for analysis at the given time point. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Weeks 8,16,24 |
| |||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Fatigue Visual Analogue Scale (VAS) at Weeks 8, 16, and 24 | The fatigue VAS is a single-item, patient-reported outcome that measures the severity of the fatigue over the past week. Patients rate their fatigue on a scale of 0 (fatigue is no problem) to 100 (fatigue is a major problem). Higher scores represent higher disease activity and a negative change from baseline indicates improvement. | Intent-to-treat population includes all participants who received at least 1 dose of study drug. Patients were included in the treatment group to which they were randomized or assigned, regardless of the treatment actually received. "n" in each of the categories is the number of participants with data available for analysis at the given time point. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Weeks 8,16,24 |
|
Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks)
Safety population. Patients were included in the TCZ dose group according to the first infusion they actually received. Patients were assigned as using a nonbiologic DMARD if they took at least 1 dose of nonbiologic DMARD during the treatment period. Patients who did not take at least 1 dose of nonbiologic DMARD were considered as on monotherapy.
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 8 mg/kg Monotherapy | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. | 11 | 138 | 63 | 138 | ||
| EG001 | Tocilizumab 4 mg/kg + DMARD | Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. | 45 | 364 | 185 | 364 | ||
| EG002 | Tocilizumab 8 mg/kg + DMARD | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. | 40 | 381 | 189 | 381 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Abscess intestinal | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Arthritis bacterial | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Bursitis infective | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Clostridial infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Empyema | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Epiglottitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Osteomyelitis acute | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Pelvic abscess | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Pneumonia streptococcal | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Subcutaneous abscess | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Large intestine perforation | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Colitis ischaemic | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Crohn's disease | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hiatus hernia | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Oesophageal spasm | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Oesophagitis haemorrhagic | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Rectal ulcer | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Sick sinus syndrome | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Muscle strain | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Patella fracture | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Joint destruction | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Spinal column stenosis | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Temporomandibular joint syndrome | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Acute prerenal failure | Renal and urinary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Vesical fistula | Renal and urinary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Aortic aneurysm | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Thrombophlebitis superficial | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Knee arthroplasty | Surgical and medical procedures | MedDRA (14.0) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Cellulitis staphylococcal | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Pneumonia pneumococcal | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Pyothorax | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Small intestinal perforation | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Cardiac valve rupture | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Traumatic haematoma | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Renal tubular necrosis | Renal and urinary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Breast cancer in situ | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.0) | Systematic Assessment |
| |
| Lung neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.0) | Systematic Assessment |
| |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.0) | Systematic Assessment |
| |
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Skin mass | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Forearm fracture | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Hypercoagulation | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (14.0) | 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 | Hoffman-LaRoche | 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
Not provided
| Insufficient therapeutic response |
|
| Protocol Violation |
|
| Refused treatment/did not cooperate |
|
| Failure to return |
|
| Administrative |
|
| Male |
|
| OG002 | Tocilizumab 8 mg/kg + DMARD | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. |
|
|
| OG002 | Tocilizumab 8 mg/kg + DMARD | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. |
|
|
| OG002 | Tocilizumab 8 mg/kg + DMARD | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. |
|
|
| OG002 | Tocilizumab 8 mg/kg + DMARD | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. |
|
|
| OG002 | Tocilizumab 8 mg/kg + DMARD | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. |
|
|
|
|
|
|
| OG002 | Tocilizumab 8 mg/kg + DMARD | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. |
|
|
| OG002 | Tocilizumab 8 mg/kg + DMARD | Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusion plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. The dosage could be decreased to 4 mg/kg for safety reasons at the investigator's discretion. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase. |
|
|