A Study Of Tocilizumab in Patients With Moderate to Severe Active Rheumatoid Arthritis Who Have an Inadequate Response to or Are Unable to Tolerate Biologic and Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs)
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT00891020
Collaborator
(none)
886
227
3
22
3.9
0.2
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
886 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab in Patients With Active Rheumatoid Arthritis on Background Non-biologic DMARDs and Monotherapy Who Have an Inadequate Response to Current Non-Biologic or Biologic DMARDs
Study Start Date
:
May 1, 2009
Actual Primary Completion Date
:
Jul 1, 2010
Actual Study Completion Date
:
Mar 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 at the investigator's discretion. |
Drug: tocilizumab [RoActemra/Actemra]
8 mg/kg intravenous every 4 weeks for 24 weeks
|
| Experimental: 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 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. |
Drug: tocilizumab [RoActemra/Actemra]
8 mg/kg intravenous every 4 weeks for 24 weeks
Drug: tocilizumab [RoActemra/Actemra]
4 mg/kg every 4 weeks for 24 weeks
Drug: Nonbiologic DMARDs of investigator's choice
Nonbiologic disease-modifying antirheumatic drugs (DMARDs) As prescribed
|
| Experimental: Tocilizumab 8 mg/kg + DMARD 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. |
Drug: tocilizumab [RoActemra/Actemra]
8 mg/kg intravenous every 4 weeks for 24 weeks
Drug: Nonbiologic DMARDs of investigator's choice
Nonbiologic disease-modifying antirheumatic drugs (DMARDs) As prescribed
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Experiencing at Least One Serious Adverse Event (SAE) During the 24 Week Treatment Period [24 Weeks]
An SAE was any adverse event that at any dose fulfilled at least one of the following criteria: Was fatal (results in death) Was life-threatening Required in-patient hospitalization or prolongation of existing hospitalization Resulted in persistent or significant disability/incapacity Was a congenital anomaly/birth defect Was medically significant or required intervention to prevent one or other of the outcomes listed above.
Secondary Outcome Measures
- Percentage of Participants Experiencing Serious Adverse Events of Special Interest [24 Weeks]
Serious Adverse Events of Special interest include: Serious infections including opportunistic infections Complications of diverticulitis (including lower gastrointestinal [GI] perforations) Myocardial infarction/acute coronary syndrome Stroke Spontaneous or serious bleeding Malignant neoplasms
- Percentage of Participants Experiencing Non-serious Adverse Events of Special Interest [24 Weeks]
Non-serious adverse Events of Special interest include: Serious/Medically Significant Hepatic Events Spontaneous /Serious Bleeding Malignant Neoplasms
- Percentage of Participants Achieving Clinical Remission at Weeks 8, 16, and 24 [Weeks 8,16,24]
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.
- Change From Baseline in DAS28 Score at Weeks 8, 16 and 24 [Baseline, Weeks 8,16,24]
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.
- Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24 [Baseline, Weeks 8,16,24]
The ACR response rates ACR20, ACR50, and ACR70 are defined as ≥20%, ≥50%, and ≥70% improvement from baseline, respectively, in: Swollen Joint Count (66 joints) and Tender Joint Count (68 joints) and At least 3 of the following 5 assessments: Patient's global assessment of pain-Visual Analog Scale (VAS) Patient global assessment of disease activity-(VAS) Physician global assessment of disease activity-(VAS) Patient assessment of disability (physical function scale of the Multidimensional Health Assessment Questionnaire) Acute phase response C-Reactive Protein (CRP)
- Percentage of Participants With Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Week 8 [Baseline, 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.
- Number of Participants Having Their Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Weeks 12, 16, and 20 [Weeks 12,16, 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.
- Change From Baseline in Routine Assessment Patient Index Data (RAPID3) Score at Weeks 8, 16, and 24 [Baseline, Weeks 8,16,24]
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.
- Change From Baseline in Fatigue Visual Analogue Scale (VAS) at Weeks 8, 16, and 24 [Baseline, Weeks 8,16,24]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
adult patients, >=18 years of age;
-
moderate to severe active rheumatoid arthritis for >6 months;
-
inadequate clinical response or unable to tolerate current or prior biologic or non-biologic Disease-modifying antirheumatic drug (DMARD) therapy;
-
Swollen joint count (SJC) >/=4 and Tender joint count (TJC) >/=4
-
body weight </=150kg
-
current permitted non-biologic DMARDs must be on stable dose for >/= 7 weeks prior to baseline;
Exclusion Criteria:
-
history of autoimmune disease or inflammatory joint disease other than rheumatoid arthritis;
-
functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in rheumatoid arthritis;
-
treatment with rituximab within 6 months before screening;
-
intraarticular corticosteroids within 8 weeks or intramuscular (im)/ intravenous (iv) corticosteroids within 12 weeks prior to screening;
-
known active current or history of recurrent infections, or any major episode of infection requiring hospitalization or treatment with iv antibiotics within 4 weeks of screening, or oral antibiotics within 2 weeks prior to screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Anniston | Alabama | United States | 36207 | |
| 2 | Birmingham | Alabama | United States | 35205 | |
| 3 | Birmingham | Alabama | United States | 35294 | |
| 4 | Huntsville | Alabama | United States | 35801 | |
| 5 | Mobile | Alabama | United States | 36608 | |
| 6 | Montgomery | Alabama | United States | 36111 | |
| 7 | Tuscaloosa | Alabama | United States | 35406 | |
| 8 | Hot Springs | Arizona | United States | 71913 | |
| 9 | Paradise Valley | Arizona | United States | 85253 | |
| 10 | Peoria | Arizona | United States | 85381 | |
| 11 | Scottsdale | Arizona | United States | 85251 | |
| 12 | Scottsdale | Arizona | United States | 85258 | |
| 13 | Tucson | Arizona | United States | 85704 | |
| 14 | Fayetteville | Arkansas | United States | 27203 | |
| 15 | Fort Smith | Arkansas | United States | 72903 | |
| 16 | Jonesboro | Arkansas | United States | 72401 | |
| 17 | Little Rock | Arkansas | United States | 72205 | |
| 18 | Covina | California | United States | 91723 | |
| 19 | Escondido | California | United States | 92025 | |
| 20 | Fullerton | California | United States | 92835 | |
| 21 | Huntington Beach | California | United States | 92646 | |
| 22 | La Jolla | California | United States | 92037 | |
| 23 | Lakewood | California | United States | 90712 | |
| 24 | Long Beach | California | United States | 90808 | |
| 25 | Los Angeles | California | United States | 90048 | |
| 26 | Murrieta | California | United States | 92563 | |
| 27 | Newport Beach | California | United States | 92663 | |
| 28 | Pasadena | California | United States | 91107 | |
| 29 | Sacramento | California | United States | 95825 | |
| 30 | San Diego | California | United States | 92108 | |
| 31 | San Leandro | California | United States | 94578 | |
| 32 | Santa Barbara | California | United States | 93108 | |
| 33 | Santa Maria | California | United States | 93454 | |
| 34 | Sherman Oaks | California | United States | 91423 | |
| 35 | Van Nuys | California | United States | 91405 | |
| 36 | Victorville | California | United States | 92295 | |
| 37 | Westlake Village | California | United States | 91361 | |
| 38 | Whittier | California | United States | 90606 | |
| 39 | Colorado Springs | Colorado | United States | 80910 | |
| 40 | Denver | Colorado | United States | 80230 | |
| 41 | Bridgeport | Connecticut | United States | 06606 | |
| 42 | Danbury | Connecticut | United States | 06810 | |
| 43 | Hamden | Connecticut | United States | 06518 | |
| 44 | Trumbull | Connecticut | United States | 06611 | |
| 45 | Lewes | Delaware | United States | 19958 | |
| 46 | Aventura | Florida | United States | 33180 | |
| 47 | Boca Raton | Florida | United States | 33486 | |
| 48 | Clearwater | Florida | United States | 33761 | |
| 49 | Dunedin | Florida | United States | 34698 | |
| 50 | Fort Lauderdale | Florida | United States | 33334 | |
| 51 | Gainesville | Florida | United States | 30501 | |
| 52 | Gainesville | Florida | United States | 32608 | |
| 53 | Jacksonville | Florida | United States | 32209 | |
| 54 | Lake Mary | Florida | United States | 32746 | |
| 55 | Melbourne | Florida | United States | 32901 | |
| 56 | Miami | Florida | United States | 33126 | |
| 57 | Miami | Florida | United States | 33133 | |
| 58 | Naples | Florida | United States | 34102 | |
| 59 | Ocala | Florida | United States | 34474 | |
| 60 | Orlando | Florida | United States | 32806 | |
| 61 | Palm Harbor | Florida | United States | 34684 | |
| 62 | Sarasota | Florida | United States | 34239 | |
| 63 | South Miami | Florida | United States | 33143 | |
| 64 | St. Petersburg | Florida | United States | 33710 | |
| 65 | Tampa | Florida | United States | 33614 | |
| 66 | Tampa | Florida | United States | 33618 | |
| 67 | Atlanta | Georgia | United States | 30342 | |
| 68 | Gainesville | Georgia | United States | 30501 | |
| 69 | Boise | Idaho | United States | 83702 | |
| 70 | Idaho Falls | Idaho | United States | 83404 | |
| 71 | Nampa | Idaho | United States | 83686 | |
| 72 | Chicago | Illinois | United States | 60616 | |
| 73 | Maywood | Illinois | United States | 60153 | |
| 74 | Moline | Illinois | United States | 61265 | |
| 75 | Morton Grove | Illinois | United States | 60053 | |
| 76 | Peoria | Illinois | United States | 61602 | |
| 77 | Schaumburg | Illinois | United States | 60195 | |
| 78 | Springfield | Illinois | United States | 62704 | |
| 79 | Vernon Hills | Illinois | United States | 60061 | |
| 80 | Evansville | Indiana | United States | 47714 | |
| 81 | Fort Wayne | Indiana | United States | 46804 | |
| 82 | South Bend | Indiana | United States | 46601 | |
| 83 | Cedar Rapids | Iowa | United States | 52401 | |
| 84 | Lees Summit | Kansas | United States | 64086 | |
| 85 | Wichita | Kansas | United States | 67208 | |
| 86 | Lexington | Kentucky | United States | 40515 | |
| 87 | Baton Rouge | Louisiana | United States | 70808 | |
| 88 | Baton Rouge | Louisiana | United States | 70810 | |
| 89 | Monroe | Louisiana | United States | 71203 | |
| 90 | New Orleans | Louisiana | United States | 70121 | |
| 91 | Columbia | Maryland | United States | 21045 | |
| 92 | Ellicott City | Maryland | United States | 21042 | |
| 93 | Frederick | Maryland | United States | 21702 | |
| 94 | Wheaton | Maryland | United States | 20902 | |
| 95 | Boston | Massachusetts | United States | 02115 | |
| 96 | Fall River | Massachusetts | United States | 02720 | |
| 97 | Pascagoula | Massachusetts | United States | 39581 | |
| 98 | Peabody | Massachusetts | United States | 01960 | |
| 99 | Plymouth | Massachusetts | United States | 02360 | |
| 100 | Worcester | Massachusetts | United States | 01605 | |
| 101 | Worcester | Massachusetts | United States | 01610 | |
| 102 | Battle Creek | Michigan | United States | 49015 | |
| 103 | Kalamazoo | Michigan | United States | 49048 | |
| 104 | Lansing | Michigan | United States | 48910 | |
| 105 | Petoskey | Michigan | United States | 49770 | |
| 106 | St Clair Shores | Michigan | United States | 48080 | |
| 107 | Duluth | Minnesota | United States | 55805 | |
| 108 | Eagan | Minnesota | United States | 55121 | |
| 109 | Edina | Minnesota | United States | 55435 | |
| 110 | St. Louis Park | Minnesota | United States | 55426 | |
| 111 | Flowood | Mississippi | United States | 39232 | |
| 112 | Hattiesburg | Mississippi | United States | 39402 | |
| 113 | Jackson | Mississippi | United States | 39202 | |
| 114 | Tupelo | Mississippi | United States | 38802 | |
| 115 | Florissant | Missouri | United States | 63031 | |
| 116 | Saint Louis | Missouri | United States | 63117 | |
| 117 | Saint Louis | Missouri | United States | 63128 | |
| 118 | St Louis | Missouri | United States | 63110 | |
| 119 | St Louis | Missouri | United States | 63141 | |
| 120 | Kalispell | Montana | United States | 59901 | |
| 121 | Grand Island | Nebraska | United States | 68803 | |
| 122 | Lincoln | Nebraska | United States | 68516 | |
| 123 | Reno | Nevada | United States | 89502 | |
| 124 | Dover | New Hampshire | United States | 03820 | |
| 125 | Lebanon | New Hampshire | United States | 03756 | |
| 126 | Clifton | New Jersey | United States | 07012 | |
| 127 | Haddon Heights | New Jersey | United States | 08035 | |
| 128 | Manalapan | New Jersey | United States | 07726 | |
| 129 | Morristown | New Jersey | United States | 07962 | |
| 130 | New Brunswick | New Jersey | United States | 08903 | |
| 131 | Trenton | New Jersey | United States | 08360 | |
| 132 | Voorhees | New Jersey | United States | 08043 | |
| 133 | Las Cruces | New Mexico | United States | 88011 | |
| 134 | Albany | New York | United States | 12206 | |
| 135 | Binghamton | New York | United States | 13905 | |
| 136 | Brooklyn | New York | United States | 11201 | |
| 137 | Cooperstown | New York | United States | 13326 | |
| 138 | Hewlett | New York | United States | 11557 | |
| 139 | Lake Success | New York | United States | 11042 | |
| 140 | New York | New York | United States | 10016 | |
| 141 | Olean | New York | United States | 14760 | |
| 142 | Orchard Park | New York | United States | 14127 | |
| 143 | Plainview | New York | United States | 11803 | |
| 144 | Rochester | New York | United States | 14618 | |
| 145 | Roslyn | New York | United States | 11576 | |
| 146 | Smithtown | New York | United States | 11787 | |
| 147 | Syracuse | New York | United States | 13210 | |
| 148 | Utica | New York | United States | 13504 | |
| 149 | Asheville | North Carolina | United States | 28803 | |
| 150 | Belmont | North Carolina | United States | 28012 | |
| 151 | Charlotte | North Carolina | United States | 28204 | |
| 152 | Charlotte | North Carolina | United States | 28207 | |
| 153 | Charlotte | North Carolina | United States | 28210 | |
| 154 | Durham | North Carolina | United States | 27704 | |
| 155 | Greenville | North Carolina | United States | 27834 | |
| 156 | Raleigh | North Carolina | United States | 27609 | |
| 157 | Rock Hill | North Carolina | United States | 29732 | |
| 158 | Wilmington | North Carolina | United States | 28401 | |
| 159 | Bismarck | North Dakota | United States | 58501 | |
| 160 | Akron | Ohio | United States | 44333 | |
| 161 | Cincinnati | Ohio | United States | 45219 | |
| 162 | Cincinnati | Ohio | United States | 45255 | |
| 163 | Columbus | Ohio | United States | 43210 | |
| 164 | Columbus | Ohio | United States | 43215 | |
| 165 | Dayton | Ohio | United States | 45402 | |
| 166 | Gallipolis | Ohio | United States | 45631 | |
| 167 | Mayfield | Ohio | United States | 44143 | |
| 168 | Middleburg Heights | Ohio | United States | 44130 | |
| 169 | Perryburg | Ohio | United States | 43551 | |
| 170 | Zanesville | Ohio | United States | 43701 | |
| 171 | Oklahoma City | Oklahoma | United States | 73103 | |
| 172 | Oklahoma City | Oklahoma | United States | 73109 | |
| 173 | Tulsa | Oklahoma | United States | 74135 | |
| 174 | Lake Oswego | Oregon | United States | 97035 | |
| 175 | Bethlehem | Pennsylvania | United States | 18015 | |
| 176 | Camp Hill | Pennsylvania | United States | 17011 | |
| 177 | Duncansville | Pennsylvania | United States | 16635 | |
| 178 | Lebanon | Pennsylvania | United States | 17042 | |
| 179 | Philadelphia | Pennsylvania | United States | 19141 | |
| 180 | Philadelphia | Pennsylvania | United States | 19152 | |
| 181 | Pottstown | Pennsylvania | United States | 19464 | |
| 182 | West Reading | Pennsylvania | United States | 19611 | |
| 183 | Wexford | Pennsylvania | United States | 15090 | |
| 184 | Willow Grove | Pennsylvania | United States | 19090 | |
| 185 | Charleston | South Carolina | United States | 29406 | |
| 186 | Columbia | South Carolina | United States | 29204 | |
| 187 | Hickory | South Carolina | United States | 28602 | |
| 188 | Myrtle Beach | South Carolina | United States | 29572 | |
| 189 | Hendersonville | Tennessee | United States | 37073 | |
| 190 | Hixson | Tennessee | United States | 37343 | |
| 191 | Jackson | Tennessee | United States | 38305 | |
| 192 | Knoxville | Tennessee | United States | 37909 | |
| 193 | Nashville | Tennessee | United States | 37027 | |
| 194 | Amarillo | Texas | United States | 79106 | |
| 195 | Amarillo | Texas | United States | 79124 | |
| 196 | Austin | Texas | United States | 78705 | |
| 197 | Austin | Texas | United States | 78749 | |
| 198 | Carrollton | Texas | United States | 75007 | |
| 199 | Dallas | Texas | United States | 75231-4406 | |
| 200 | Dallas | Texas | United States | 75231 | |
| 201 | Dallas | Texas | United States | 75246 | |
| 202 | Fort Worth | Texas | United States | 76107 | |
| 203 | Houston | Texas | United States | 77074 | |
| 204 | Houston | Texas | United States | 77090 | |
| 205 | Lubbock | Texas | United States | 79424 | |
| 206 | Mesquite | Texas | United States | 75150 | |
| 207 | Nassau Bay | Texas | United States | 77058 | |
| 208 | San Antonio | Texas | United States | 78217 | |
| 209 | San Antonio | Texas | United States | 78229 | |
| 210 | San Antonio | Texas | United States | 78258 | |
| 211 | Tyler | Texas | United States | 75701 | |
| 212 | Waco | Texas | United States | 76708 | |
| 213 | Burlington | Vermont | United States | 05401 | |
| 214 | Arlington | Virginia | United States | 22205 | |
| 215 | Burke | Virginia | United States | 22015 | |
| 216 | Richmond | Virginia | United States | 23294 | |
| 217 | Virginia Beach | Virginia | United States | 23454 | |
| 218 | Olympia | Washington | United States | 98502 | |
| 219 | Spokane | Washington | United States | 99204 | |
| 220 | Tacoma | Washington | United States | 98405 | |
| 221 | Beckley | West Virginia | United States | 25801 | |
| 222 | Clarksburg | West Virginia | United States | 26301 | |
| 223 | Brookfield | Wisconsin | United States | 53045 | |
| 224 | Franklin | Wisconsin | United States | 53132 | |
| 225 | Glendale | Wisconsin | United States | 53217 | |
| 226 | Milwaukee | Wisconsin | United States | 53209 | |
| 227 | Onalaska | Wisconsin | United States | 54605 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00891020
Other Study ID Numbers:
- ML22533
First Posted:
Apr 30, 2009
Last Update Posted:
Oct 25, 2012
Last Verified:
Oct 1, 2012
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 1129 patients were screened for the study. Of these 1129 patients, 886 patients were enrolled and 243 patients were screen failures. |
| Arm/Group Title | Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Period Title: 24 Week Treatment Period | |||
| STARTED | 163 | 363 | 360 |
| Intent-to-Treat (ITT) | 163 | 362 | 358 |
| Safety Set | 138 | 364 | 381 |
| COMPLETED | 126 | 303 | 302 |
| NOT COMPLETED | 37 | 60 | 58 |
| Period Title: 24 Week Treatment Period | |||
| STARTED | 55 | 196 | 193 |
| COMPLETED | 49 | 172 | 170 |
| NOT COMPLETED | 6 | 24 | 23 |
Baseline Characteristics
| Arm/Group Title | Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 138 | 364 | 381 | 883 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
53.5
(12.63)
|
55.6
(11.92)
|
54.0
(12.11)
|
54.6
(12.13)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
110
79.7%
|
273
75%
|
296
77.7%
|
679
76.9%
|
| Male |
28
20.3%
|
91
25%
|
85
22.3%
|
204
23.1%
|
Outcome Measures
| Title | Percentage of Participants Experiencing at Least One Serious Adverse Event (SAE) During the 24 Week Treatment Period |
|---|---|
| Description | An SAE was any adverse event that at any dose fulfilled at least one of the following criteria: Was fatal (results in death) Was life-threatening Required in-patient hospitalization or prolongation of existing hospitalization Resulted in persistent or significant disability/incapacity Was a congenital anomaly/birth defect Was medically significant or required intervention to prevent one or other of the outcomes listed above. |
| Time Frame | 24 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD |
|---|---|---|---|
| Arm/Group Description | Participants received Tocilizumab (TCZ) 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. | 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. | 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. |
| Measure Participants | 138 | 364 | 381 |
| Number [Percentage of Participants] |
5.8
4.2%
|
8.0
2.2%
|
8.4
2.2%
|
| Title | Percentage of Participants Experiencing Serious Adverse Events of Special Interest |
|---|---|
| Description | Serious Adverse Events of Special interest include: Serious infections including opportunistic infections Complications of diverticulitis (including lower gastrointestinal [GI] perforations) Myocardial infarction/acute coronary syndrome Stroke Spontaneous or serious bleeding Malignant neoplasms |
| Time Frame | 24 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 138 | 364 | 381 |
| Serious Infections (including opportunistic) |
2.9
2.1%
|
3.6
1%
|
3.9
1%
|
| Gastrointestinal Perforations and Related Events |
0
0%
|
0.8
0.2%
|
0
0%
|
| Myocardial Infarction/Acute Coronary Syndrome |
0
0%
|
0
0%
|
0.3
0.1%
|
| Stroke |
0
0%
|
0.3
0.1%
|
0
0%
|
| Spontaneous/Serious Bleeding |
0
0%
|
0.3
0.1%
|
0.3
0.1%
|
| Malignant Neoplasms |
0
0%
|
0
0%
|
0.3
0.1%
|
| Title | Percentage of Participants Experiencing Non-serious Adverse Events of Special Interest |
|---|---|
| Description | Non-serious adverse Events of Special interest include: Serious/Medically Significant Hepatic Events Spontaneous /Serious Bleeding Malignant Neoplasms |
| Time Frame | 24 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 138 | 364 | 381 |
| Serious/Medically Significant Hepatic Events |
0
0%
|
0
0%
|
0.3
0.1%
|
| Spontaneous/Serious Bleeding |
4.3
3.1%
|
3.3
0.9%
|
7.3
1.9%
|
| Malignant Neoplasms |
0
0%
|
0.3
0.1%
|
0.3
0.1%
|
| Title | Percentage of Participants Achieving Clinical Remission at Weeks 8, 16, and 24 |
|---|---|
| Description | 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. |
| Time Frame | Weeks 8,16,24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 163 | 362 | 358 |
| Week 8 (n=147, 337, 334) |
8.8
6.4%
|
6.8
1.9%
|
12.9
3.4%
|
| Week 16 (n=127, 317, 304) |
15.7
11.4%
|
17.4
4.8%
|
22.0
5.8%
|
| Week 24 (n=126, 286, 302) |
19.8
14.3%
|
20.6
5.7%
|
25.2
6.6%
|
| Title | Change From Baseline in DAS28 Score at Weeks 8, 16 and 24 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Weeks 8,16,24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 163 | 362 | 358 |
| Week 8 (n=147, 337, 334) |
-1.75
(1.213)
|
-1.00
(1.189)
|
-1.54
(1.187)
|
| Week 16 (n=127, 317, 304) |
-2.07
(1.406)
|
-1.66
(1.244)
|
-1.87
(1.322)
|
| Week 24 (n=126, 286, 302) |
-2.03
(1.384)
|
-1.81
(1.264)
|
-1.94
(1.380)
|
| Title | Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24 |
|---|---|
| Description | The ACR response rates ACR20, ACR50, and ACR70 are defined as ≥20%, ≥50%, and ≥70% improvement from baseline, respectively, in: Swollen Joint Count (66 joints) and Tender Joint Count (68 joints) and At least 3 of the following 5 assessments: Patient's global assessment of pain-Visual Analog Scale (VAS) Patient global assessment of disease activity-(VAS) Physician global assessment of disease activity-(VAS) Patient assessment of disability (physical function scale of the Multidimensional Health Assessment Questionnaire) Acute phase response C-Reactive Protein (CRP) |
| Time Frame | Baseline, Weeks 8,16,24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 163 | 362 | 358 |
| Week 8 ACR20 responders |
40.5
29.3%
|
37.8
10.4%
|
40.8
10.7%
|
| Week 8 ACR50 responders |
14.7
10.7%
|
11.9
3.3%
|
16.8
4.4%
|
| Week 8 ACR70 responders |
4.3
3.1%
|
3.3
0.9%
|
5.6
1.5%
|
| Week 16 ACR20 responders |
46.6
33.8%
|
43.9
12.1%
|
45.3
11.9%
|
| Week 16 ACR50 responders |
23.3
16.9%
|
19.9
5.5%
|
22.3
5.9%
|
| Week 16 ACR70 responders |
7.4
5.4%
|
8.6
2.4%
|
9.8
2.6%
|
| Week 24 ACR20 responders |
47.9
34.7%
|
44.8
12.3%
|
49.7
13%
|
| Week 24 ACR50 responders |
24.5
17.8%
|
24.3
6.7%
|
27.1
7.1%
|
| Week 24 ACR70 responders |
7.4
5.4%
|
8.8
2.4%
|
10.3
2.7%
|
| Title | Percentage of Participants With Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Week 8 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Tocilizumab 4 mg/kg + DMARD |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 364 |
| Number [Percentage of Participants] |
39.9
28.9%
|
| Title | Number of Participants Having Their Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Weeks 12, 16, and 20 |
|---|---|
| Description | 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. |
| Time Frame | Weeks 12,16, 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Tocilizumab 4 mg/kg + DMARD |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 364 |
| Week 12 (n=183) |
41
29.7%
|
| Week 16 (n=138) |
18
13%
|
| Week 20 (n=119) |
5
3.6%
|
| Title | Change From Baseline in Routine Assessment Patient Index Data (RAPID3) Score at Weeks 8, 16, and 24 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Weeks 8,16,24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 163 | 362 | 358 |
| Week 8 (n=156, 348, 343) |
-1.60
(1.803)
|
-1.10
(1.848)
|
-1.28
(1.733)
|
| Week 16 (n=138, 325, 315) |
-1.97
(2.068)
|
-1.42
(1.896)
|
-1.46
(1.897)
|
| Week 24 (n=134, 306, 308) |
-1.83
(1.978)
|
-1.61
(1.972)
|
-1.46
(1.962)
|
| Title | Change From Baseline in Fatigue Visual Analogue Scale (VAS) at Weeks 8, 16, and 24 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Weeks 8,16,24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 163 | 362 | 358 |
| Week 8 (n=156, 350, 344) |
-13.17
(25.584)
|
-10.06
(25.349)
|
-13.33
(24.950)
|
| Week 16 (n=138, 329, 317) |
-19.38
(26.639)
|
-14.00
(26.282)
|
-15.58
(25.802)
|
| Week 24 (n=135, 307, 312) |
-15.85
(26.881)
|
-16.73
(26.261)
|
-16.07
(26.321)
|
Adverse Events
| Time Frame | Includes Adverse Events that occurred during the 24-week Treatment Period and the Long-term Extension Period (up to 72 Weeks) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||||
| Arm/Group Title | Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD | |||
| Arm/Group Description | 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. | 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. | 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. | |||
All Cause Mortality |
||||||
| Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/138 (8%) | 45/364 (12.4%) | 40/381 (10.5%) | |||
| Blood and lymphatic system disorders | ||||||
| Hypercoagulation | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Cardiac disorders | ||||||
| Cardiac failure congestive | 0/138 (0%) | 2/364 (0.5%) | 1/381 (0.3%) | |||
| Coronary artery disease | 0/138 (0%) | 2/364 (0.5%) | 1/381 (0.3%) | |||
| Acute myocardial infarction | 0/138 (0%) | 1/364 (0.3%) | 1/381 (0.3%) | |||
| Cardiac arrest | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Sick sinus syndrome | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Arrhythmia | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Atrial fibrillation | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Ventricular tachycardia | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Endocrine disorders | ||||||
| Adrenal insufficiency | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Gastrointestinal disorders | ||||||
| Large intestine perforation | 0/138 (0%) | 3/364 (0.8%) | 0/381 (0%) | |||
| Small intestinal obstruction | 1/138 (0.7%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Aphthous stomatitis | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Colitis ischaemic | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Crohn's disease | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Hiatus hernia | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Oesophageal spasm | 1/138 (0.7%) | 0/364 (0%) | 0/381 (0%) | |||
| Oesophagitis haemorrhagic | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Rectal ulcer | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Gastrointestinal haemorrhage | 1/138 (0.7%) | 0/364 (0%) | 0/381 (0%) | |||
| Small intestinal perforation | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| General disorders | ||||||
| Chest pain | 1/138 (0.7%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Pyrexia | 1/138 (0.7%) | 0/364 (0%) | 0/381 (0%) | |||
| Non-cardiac chest pain | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Infections and infestations | ||||||
| Pneumonia | 1/138 (0.7%) | 5/364 (1.4%) | 8/381 (2.1%) | |||
| Cellulitis | 2/138 (1.4%) | 6/364 (1.6%) | 3/381 (0.8%) | |||
| Osteomyelitis | 0/138 (0%) | 2/364 (0.5%) | 0/381 (0%) | |||
| Sepsis | 0/138 (0%) | 0/364 (0%) | 2/381 (0.5%) | |||
| Abscess intestinal | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Arthritis bacterial | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Bronchitis | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Bursitis infective | 0/138 (0%) | 1/364 (0.3%) | 1/381 (0.3%) | |||
| Clostridial infection | 1/138 (0.7%) | 0/364 (0%) | 0/381 (0%) | |||
| Empyema | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Epiglottitis | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Gastroenteritis viral | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Herpes zoster | 1/138 (0.7%) | 0/364 (0%) | 0/381 (0%) | |||
| Localised infection | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Osteomyelitis acute | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Pelvic abscess | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Pneumonia streptococcal | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Subcutaneous abscess | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Septic shock | 0/138 (0%) | 1/364 (0.3%) | 1/381 (0.3%) | |||
| Cellulitis staphylococcal | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Cystitis | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Infection | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Pneumonia pneumococcal | 1/138 (0.7%) | 0/364 (0%) | 0/381 (0%) | |||
| Pyothorax | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Staphylococcal infection | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Femur fracture | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Humerus fracture | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Muscle strain | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Patella fracture | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Upper limb fracture | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Wrist fracture | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Cardiac valve rupture | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Traumatic haematoma | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Forearm fracture | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Infusion related reaction | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Hypokalaemia | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Malnutrition | 1/138 (0.7%) | 0/364 (0%) | 0/381 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Joint destruction | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Osteoarthritis | 0/138 (0%) | 2/364 (0.5%) | 1/381 (0.3%) | |||
| Rheumatoid arthritis | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Spinal column stenosis | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Temporomandibular joint syndrome | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Intervertebral disc protrusion | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Breast cancer | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Breast cancer in situ | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Lung neoplasm | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Lung neoplasm malignant | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Nervous system disorders | ||||||
| Cerebrovascular accident | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Paraesthesia | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Syncope | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Psychiatric disorders | ||||||
| Depression | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Renal and urinary disorders | ||||||
| Renal failure acute | 0/138 (0%) | 1/364 (0.3%) | 1/381 (0.3%) | |||
| Acute prerenal failure | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Nephrolithiasis | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Vesical fistula | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Renal tubular necrosis | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Chronic obstructive pulmonary disease | 1/138 (0.7%) | 1/364 (0.3%) | 1/381 (0.3%) | |||
| Asthma | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Interstitial lung disease | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Pleural effusion | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Pneumonitis | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Pulmonary embolism | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Pulmonary fibrosis | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Decubitus ulcer | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Skin mass | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Surgical and medical procedures | ||||||
| Knee arthroplasty | 0/138 (0%) | 0/364 (0%) | 1/381 (0.3%) | |||
| Vascular disorders | ||||||
| Aortic aneurysm | 0/138 (0%) | 1/364 (0.3%) | 1/381 (0.3%) | |||
| Haematoma | 0/138 (0%) | 1/364 (0.3%) | 1/381 (0.3%) | |||
| Thrombophlebitis superficial | 0/138 (0%) | 1/364 (0.3%) | 0/381 (0%) | |||
| Hypertension | 1/138 (0.7%) | 0/364 (0%) | 0/381 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Tocilizumab 8 mg/kg Monotherapy | Tocilizumab 4 mg/kg + DMARD | Tocilizumab 8 mg/kg + DMARD | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 63/138 (45.7%) | 185/364 (50.8%) | 189/381 (49.6%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 9/138 (6.5%) | 25/364 (6.9%) | 14/381 (3.7%) | |||
| Nausea | 5/138 (3.6%) | 25/364 (6.9%) | 16/381 (4.2%) | |||
| General disorders | ||||||
| Chest pain | 7/138 (5.1%) | 4/364 (1.1%) | 1/381 (0.3%) | |||
| Infections and infestations | ||||||
| Upper respiratory tract infection | 14/138 (10.1%) | 36/364 (9.9%) | 41/381 (10.8%) | |||
| Sinusitis | 11/138 (8%) | 33/364 (9.1%) | 36/381 (9.4%) | |||
| Nasopharyngitis | 7/138 (5.1%) | 31/364 (8.5%) | 19/381 (5%) | |||
| Urinary tract infection | 8/138 (5.8%) | 8/364 (2.2%) | 19/381 (5%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 8/138 (5.8%) | 13/364 (3.6%) | 26/381 (6.8%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Rheumatoid arthritis | 12/138 (8.7%) | 40/364 (11%) | 32/381 (8.4%) | |||
| Arthralgia | 7/138 (5.1%) | 20/364 (5.5%) | 22/381 (5.8%) | |||
| Nervous system disorders | ||||||
| Headache | 7/138 (5.1%) | 27/364 (7.4%) | 26/381 (6.8%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 4/138 (2.9%) | 13/364 (3.6%) | 23/381 (6%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffman-LaRoche |
| Phone | 800-821-8590 |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00891020
Other Study ID Numbers:
- ML22533
First Posted:
Apr 30, 2009
Last Update Posted:
Oct 25, 2012
Last Verified:
Oct 1, 2012