A National, Open-Label, Single-Arm, Phase IIIb Study to Evaluate the Efficacy of Weekly Tocilizumab Subcutaneous, Administered as Monotherapy or in Combination With Methotrexate and/or Other DMARDs in Rheumatoid Arthritis (RA) Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 227
- 试验地点
- 49
- 主要终点
- Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
研究概览
简要总结
This open-label, single arm, Phase 3b study will evaluate the efficacy of tocilizumab (RoActemra), administered as monotherapy or in combination with methotrexate and/or other DMARDs, in participants with moderate to severe active RA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria
- •Moderate to severe RA (CDAI at least [>/=] 10 and DAS28 >/=3.2) at screening
- •Tumor necrosis factor inhibitors-inadequate responder (TNF-IR), methotrexate-inadequate responder (MTX-IR), and/or DMARDs-inadequate responder (DMARDs-IR)
- •Oral corticosteroids (less than or equal to [</=] 10 mg per day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if on a stable dose regimen for >/=4 weeks prior to baseline
- •Permitted non-biologic DMARDs are allowed if at a stable dose for >/=4 weeks prior to baseline
- •Receiving treatment on an outpatient basis, not including tocilizumab
- •Females of childbearing potential and males with female partners of childbearing potential must agree to use a reliable means of contraception for at least 3 months following the last dose of tocilizumab
排除标准
- •Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 12 months following baseline
- •Rheumatic autoimmune disease other than RA; secondary Sjögren's syndrome with RA is permitted
- •Functional Class IV as defined by the ACR Classification of Functional Status in RA
- •Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16
- •Prior history of or current inflammatory joint disease other than RA
- •Exposure to tocilizumab (either intravenous [IV] or SC) at any time prior to baseline
- •Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
- •Previous treatment with any cell-depleting therapies
- •Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
- •History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
- •Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal disease
- •Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections
- •Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening
- •Active tuberculosis (TB) requiring treatment within the previous 3 years
- •Positive for hepatitis B surface antigen or hepatitis C antibody
- •Primary or secondary immunodeficiency (history of or currently active)
- •Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (except for basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years
- •Pregnant or breast feeding women
- •Neuropathies or other conditions that might interfere with pain evaluation
研究组 & 干预措施
Tocilizumab
Tocilizumab at a fixed dose of 162 milligrams (mg) will be administered as subcutaneous (SC) injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants can continue the study treatment with SC tocilizumab until it becomes commercially available in Italy.
干预措施: Tocilizumab (Drug)
Tocilizumab
Tocilizumab at a fixed dose of 162 milligrams (mg) will be administered as subcutaneous (SC) injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants can continue the study treatment with SC tocilizumab until it becomes commercially available in Italy.
干预措施: DMARDs (Drug)
结局指标
主要结局
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
时间窗: Baseline, Week 24
The CDAI is a numerical sum of 4 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, patient's global assessment of disease activity (PtGDA) and physician global assessment of disease activity (PGDA) assessed on 0-10 centimeters (cm) visual analogue scale (VAS). Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score less than or equal to (\</=) 2.8 indicates disease remission, greater than (\>) 2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.
Change From Baseline in CDAI at Week 20
时间窗: Baseline, Week 20
The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.
Change From Baseline in CDAI at Week 16
时间窗: Baseline, Week 16
The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.
Change From Baseline in CDAI at Week 12
时间窗: Baseline, Week 12
The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.
Change From Baseline in CDAI at Week 8
时间窗: Baseline, Week 8
The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.
Change From Baseline in CDAI at Week 4
时间窗: Baseline, Week 4
The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.
Change From Baseline in CDAI at Week 2
时间窗: Baseline, Week 2
The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.
次要结局
- Number of Participants Achieving Clinical Remission According to CDAI up to Week 52(Baseline up to Week 52 (Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 38, and 52))
- Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52(Baseline, Weeks 2, 24, and 52)
- Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52(Baseline, Weeks 2, 24, and 52)
- Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response(Weeks 2, 24, and 52)
- Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28(Baseline, Weeks 2, 24, and 52)
- Change From Baseline in Total TJC at Weeks 2, 24, and 52(Baseline, Weeks 2, 24, and 52)
- Change From Baseline in Total SJC at Weeks 2, 24, and 52(Baseline, Weeks 2, 24, and 52)
- Association Between Disease Activity Parameters: DAS28-ESR and CDAI, Assessed Using Correlation Coefficient(Weeks 2, 24, 52)
- Association Between Disease Activity Parameters: DAS28-ESR and SDAI, Assessed Using Correlation Coefficient(Weeks 2, 24, 52)
- Association Between Disease Activity Parameters: CDAI and SDAI, Assessed Using Correlation Coefficient(Weeks 2, 24, 52)
- Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient(Weeks 2, 24, 52)
- Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient(Weeks 2, 24, 52)
- Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient(Weeks 2, 24, 52)
- Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient(Weeks 2, 24, 52)
- Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient(Weeks 2, 24, 52)
- Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient(Weeks 2, 24, 52)
- Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons(Baseline up to Week 52)
- Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons(Baseline up to Week 52)
- Change From Baseline in PtGDA VAS Score at Weeks 2, 24, and 52(Baseline, Weeks 2, 24, and 52)
- Change From Baseline in PGDA VAS Score at Weeks 2, 24, and 52(Baseline, Weeks 2, 24, and 52)
- Participant Pain VAS Score at Weeks 2, 24, and 52(Weeks 2, 24, and 52)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 24, and 52(Baseline, Weeks 2, 24, and 52)
- Missed Working Days Assessed Using Short Form-Health and Labor Questionnaire (SF-HLQ) Score at Weeks 24 and 52(Weeks 24 and 52)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Total Score at Weeks 2, 24, and 52(Baseline, Weeks 2, 24, and 52)
- Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) at Weeks 24 and 52(Baseline, Weeks 24 and 52)
- Treatment Compliance, as Assessed Using Participant Diary Cards and Return Records(Weeks 24 and 52)
- Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) of Special Interest(Baseline up to 95 weeks)
- Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab(Baseline, Weeks 12, 24, 38, 52, at 8 weeks after last dose (up to Week 60), at early withdrawal (up to Week 52), at Follow-up Visits 1 (Week 64), 2 (Week 76), and 3 (Week 88))
- Mean Tocilizumab Concentration(Baseline, Weeks 12, 24, 38, 52, at early withdrawal (up to Week 52), at Follow-up Visit 2 (Week 76))
- Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration(Baseline, Weeks 12, 24, 38, 52, at early withdrawal (up to Week 52), at Follow-up Visit 2 (Week 76))