A Randomized, Double-blind, Parallel Group Study of the Safety and Effect on Clinical Outcome of Tocilizumab SC Versus Tocilizumab IV, in Combination With Traditional Disease Modifying Anti-rheumatic Drugs (DMARDs), in Patients With Moderate to Severe Active Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,262
- 主要终点
- Percentage of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Assessments
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult participants, ≥ 18 years of age
- •Rheumatoid arthritis of ≥ 6 months duration, according to American College of Rheumatology (ACR) criteria
- •Swollen joint count (SJC) ≥ 4 (66 joint count), tender joint count (TJC) ≥ 4 (68 joint count) at screening and baseline
- •Inadequate response to current DMARD therapy
- •Permitted DMARDs must be at stable dose for ≥ 8 weeks prior to baseline
- •Oral corticosteroids (≤ 10 mg/day prednisone or equivalent) and NSAIDs (up to maximum recommended dose) must be at stable dose for ≥ 4 weeks prior to baseline
排除标准
- •Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization
- •Rheumatic autoimmune disease other than RA
- •Functional class IV (ACR classification)
- •Diagnosis of juvenile idiopathic arthritis (JIA) or juvenile rheumatoid arthritis (JRA) and/or RA before the age of 16
- •Prior history of or current inflammatory joint disease other than RA
- •Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
- •Previous treatment with tocilizumab
- •Active current or history of recurrent infection
研究组 & 干预措施
Tocilizumab SC
Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.
干预措施: tocilizumab SC (Drug)
Tocilizumab SC
Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.
干预措施: placebo to tocilizumab IV (Drug)
Tocilizumab SC
Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.
干预措施: Disease-modifying antirheumatic drugs (DMARDs) (Drug)
Tocilizumab IV
Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.
干预措施: tocilizumab IV (Drug)
Tocilizumab IV
Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.
干预措施: placebo to tocilizumab SC (Drug)
Tocilizumab IV
Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.
干预措施: Disease-modifying antirheumatic drugs (DMARDs) (Drug)
Tocilizumab SC Then Tocilizumab IV
Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.
干预措施: tocilizumab SC (Drug)
Tocilizumab SC Then Tocilizumab IV
Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.
干预措施: tocilizumab IV (Drug)
Tocilizumab SC Then Tocilizumab IV
Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.
干预措施: placebo to tocilizumab IV (Drug)
Tocilizumab SC Then Tocilizumab IV
Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.
干预措施: Disease-modifying antirheumatic drugs (DMARDs) (Drug)
Tocilizumab IV Then Tocilizumab SC
Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
干预措施: tocilizumab SC (Drug)
Tocilizumab IV Then Tocilizumab SC
Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
干预措施: tocilizumab IV (Drug)
Tocilizumab IV Then Tocilizumab SC
Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
干预措施: placebo to tocilizumab SC (Drug)
Tocilizumab IV Then Tocilizumab SC
Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.
干预措施: Disease-modifying antirheumatic drugs (DMARDs) (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Assessments
时间窗: 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 (ACR20) Response at Week 24
时间窗: Baseline, 24 weeks
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 \[ESR\]).
次要结局
- Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR70) Response at Week 24(Baseline, 24 weeks)
- Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR50) Response at Week 24(Baseline, 24 weeks)
- Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 24(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(Baseline, 24 Weeks)
- Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 24(24 Weeks)
- Change From Baseline in Serum Soluble Interleukin-6 Receptor (sIL-6R) Concentration at Week 97(Baseline, Week 97)
- Percentage of Participants With American College of Rheumatology Criteria (ACR20, ACR50, ACR70) at Week 97(Week 97)
- Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 97(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(Baseline, Week 97)
- Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 97(Week 97)
- Area Under the Serum Concentration Curve of Tocilizumab After First SC Injection or IV Infusion(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(Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose.)
- Percentage of Participants Who Developed Antibodies To Tocilizumab at Week 97(Week 97)
- Minimum Serum Concentration (Cmin) of Tocilizumab(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(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(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(Baseline, Week 25)