This randomized, double-blind, parallel group study compares the efficacy and safety of subcutaneous (sc) versus intravenous (iv) administration of tocilizumab in participants with moderate to severe active rheumatoid arthritis. Participants were randomized to receive either tocilizumab 162 mg sc weekly plus iv placebo every 4 weeks, or tocilizumab 8 mg/kg iv every 4 weeks plus sc placebo weekly during the double-blind period from baseline to Week 24. The double-blind period was followed by a 72-week open-label treatment with some switching of sc and iv administration. No placebo was administered in the open-label phase. Participants continued on their stable dose of disease-modifying antirheumatic drugs (DMARDs) throughout the study. Anticipated time on study treatment was 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
1,262
Tocilizumab supplied in a single-use pre-filled syringe, with a needle safety device, delivering 162 mg/0.9 mL solution for subcutaneous injection once a week.
Tocilizumab supplied in vials as a sterile solution for 8 mg/kg intravenous infusion every 4 weeks.
Placebo tocilizumab supplied as a single-use pre-filled syringe with a needle safety device, delivering 0.9 mL sodium chloride for subcutaneous injection once a week for 24 weeks in the double-blind period.
Placebo to tocilizumab supplied as a solution in 10 mL vials containing polysorbate 80 and sucrose in water for infusion every 4 weeks for a total of 24 weeks in the double-blind period.
stable dose as prescribed
Unnamed facility
Huntsville, Alabama, United States
Unnamed facility
Tuscaloosa, Alabama, United States
Unnamed facility
Tucson, Arizona, United States
Unnamed facility
Tucson, Arizona, United States
Unnamed facility
Long Beach, California, United States
Unnamed facility
Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR20) Response at Week 24
ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the five additional ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) where left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either C-reactive protein \[CRP\] or Erythrocyte Sedimentation Rate \[ESR\]).
Time frame: Baseline, 24 weeks
Percentage of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Assessments
Time frame: Baseline to up to 3 months after last dose of study drug (approximately up to 2 years)
Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR50) Response at Week 24
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the five additional ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) where left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either C-reactive protein or Erythrocyte Sedimentation Rate).
Time frame: Baseline, 24 weeks
Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR70) Response at Week 24
ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the five additional ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) where left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either C-reactive protein or Erythrocyte Sedimentation Rate).
Time frame: Baseline, 24 weeks
Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 24
The DAS28 (ESR) score is a measure of the subject's disease activity. It is calculated using the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity VAS where left side of the line 0=no disease activity to right side of the line 100=extreme disease activity and ESR. DAS28-(ESR) total scores range from 0 - 10. Remission is defined as achieving a DAS28-ESR score of less than 2.6.
Time frame: Week 24
Percentage of Participants Achieving a Decrease of ≥ 0.3 in the Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 24
The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a participant completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A decrease indicates improvement.
Time frame: Baseline, 24 Weeks
Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 24
The percentage of participants who withdrew from the study because they were not responding to treatment with the study drug.
Time frame: 24 Weeks
Percentage of Participants With American College of Rheumatology Criteria (ACR20, ACR50, ACR70) at Week 97
ACR20, ACR50 and ACR70: ≥20%, ≥50% and ≥70% reduction from baseline for both TJC68 and SJC66, as well as for 3 of 5 additional ACR variables: Patient's Assessment of Pain in last 24 hours using a Visual Analog Scale (VAS) (0=no pain and 100=unbearable pain); Patient's and Physician's Global Assessment of Disease Activity in last 24 hours using a VAS (0=no disease activity and100=maximum disease activity); Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either CRP or ESR). CRP was used for calculation of ACR. If missing, ESR was used. LOCF was used for missing joint counts, no imputation for other ACR components.
Time frame: Week 97
Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 97
The DAS28 (ESR) score is a measure of the subject's disease activity. It is calculated using the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity VAS where left side of the line 0=no disease activity to right side of the line 100=extreme disease activity and ESR. DAS28-(ESR) total scores range from 0 - 10. Remission is defined as achieving a DAS28-ESR score of less than 2.6. LOCF used for tender and swollen joint counts, no imputation used for ESR and Patient's Global Assessment of Disease Activity VAS.
Time frame: Week 97
Percentage of Participants Achieving a Decrease of ≥0.3 in the Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 97
The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A decrease indicates improvement. No imputation of missing scores was made other than for missing baseline scores, for which last score prior to baseline will be carried forward. For participants who prematurely withdrew, data collected at withdrawal visit was used and data thereafter is missing.
Time frame: Baseline, Week 97
Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 97
The percentage of participants who withdrew from the study because they were not responding to treatment with the study drug.
Time frame: Week 97
Area Under the Serum Concentration Curve of Tocilizumab After First SC Injection or IV Infusion
Time frame: Week 0: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after first dose
Area Under the Serum Concentration Curve of Tocilizumab at Steady State for SC and IV Treatment
Time frame: Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose.
Minimum Serum Concentration (Cmin) of Tocilizumab
Time frame: Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose
Maximum Serum Concentration (Cmax) of Tocilizumab
Time frame: Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose
Time to Maximum Serum Concentration (Tmax) of Tocilizumab
Time frame: Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose
Change From Baseline in Serum Interleukin-6 (IL-6) Concentration at Week 25
Time frame: Baseline, Week 25
Change From Baseline in Serum Soluble Interleukin-6 Receptor (sIL-6R) Concentration at Week 97
Time frame: Baseline, Week 97
Percentage of Participants Who Developed Antibodies To Tocilizumab at Week 97
Time frame: Week 97
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Los Angeles, California, United States
Unnamed facility
Upland, California, United States
Unnamed facility
Van Nuys, California, United States
Unnamed facility
Denver, Colorado, United States
Unnamed facility
Bridgeport, Connecticut, United States
...and 206 more locations