A Multicenter, Open-label, Long-term Extension Study of WA22762 and NA25220 to Evaluate Safety and Efficacy of Subcutaneous Tocilizumab in Patients With Moderate to Severe Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 47
- 主要终点
- Percentage of Participants Withdrawn From the Study Due to Lack of Therapeutic Response
研究概览
简要总结
This multicenter, open-label, single arm, long-term extension study will evaluate the safety and efficacy of RoActemra/Actemra (tocilizumab) in participants with moderate to severe rheumatoid arthritis who have completed the 97-week WA22762 or the 96-week NA25220 core study. Participants will receive RoActemra/Actemra 162 milligram (mg) subcutaneously weekly (for participants entering from WA22762) or every two weeks (for participants entering from NA25220) for 96 weeks, with telephone call follow-up visits at Weeks 100 and 104.
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
- •Adult participants, >/= 18 years of age
- •Participants who have completed the 97-week WA22762 or 96-week NA25220 core study on subcutaneous or intravenous RoActemra/Actemra and based on the investigator's judgment may continue to benefit from RoActemra/Actemra treatment in this study investigating the subcutaneous formulation
- •Oral corticosteroids 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-biological disease-modifying anti-rheumatic drugs (DMARDs) are allowed
- •Receiving treatment on an outpatient basis
- •Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception
排除标准
- •Participants who have prematurely withdrawn from the WA22762 or NA25220 core studies for any reason
- •Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies
- •History of severe allergic or anaphylactic reactions to human, humanized or mural monoclonal antibodies
- •Evidence of serious uncontrolled concomitant disease
- •Current liver disease as determined by the principal investigator
- •History of diverticulitis, diverticulosis requiring antibiotic treatment or chronic ulcerative lower gastrointestinal (GI) disease such as Crohn's disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations
- •Known active current or history of recurrent infections
- •Any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
- •Active tuberculosis requiring treatment within the previous 3 years
- •Primary or secondary immunodeficiency (history of or currently active)
- •Pregnant or breast feeding women
- •Body weight > 150 kilogram (kg)
- •Inadequate renal, hepatic or hematologic function
- •Positive for hepatitis B or hepatitis C
研究组 & 干预措施
Tocilizumab Subcutaneous (SC)
Participants received Tocilizumab 162 milligram (mg) given as 0.9 milliliter (mL) of a 180 milligram per milliliter (mg/mL) solution administered once a week (for participants entering from NCT01194414) or once every two weeks (for participants entering from NCT01232569) by SC injection and as a single fixed dose irrespective of body weight.
干预措施: tocilizumab (Drug)
结局指标
主要结局
Percentage of Participants Withdrawn From the Study Due to Lack of Therapeutic Response
时间窗: Baseline up to follow-up (Week 104)
Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 48
时间窗: Baseline, Week 48
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis. The index included swollen joint count (SJC), tender joint count (TJC), acute phase response (ESR or high sensitivity C-reactive protein \[hsCRP\]) and general health status (GH). For this study, ESR was used to calculate DAS28 score. The index was calculated using the following formula: DAS28 = (0.56 × √\[TJC 28\]) + (0.28 × √\[SJC 28\]) + (0.7 × ln\[ESR\]) + (0.014 × GH). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Change in DAS28ESR=DAS28-ESR at Week 48 - DAS28-ESR at Baseline.
Change From Baseline in DAS28-ESR at Week 96
时间窗: Baseline, Week 96
The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis. The index included SJC, TJC, acute phase response (ESR or high sensitivity C-reactive protein \[hsCRP\]) and general health status. For this study, ESR was used to calculate DAS28 score. The index was calculated using the following formula: DAS28 = (0.56 × √\[TJC28\]) + (0.28 × √\[SJC28\]) + (0.7 × ln\[ESR\]) + (0.014 × GH). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Change in DAS28ESR=DAS28-ESR at Week 96 - DAS28-ESR at Baseline.
Percentage of Participants With an Adverse Event (AE)
时间窗: Baseline up to follow-up (Week 104)
An AE was defined as any untoward medical occurrence in a clinical investigation participant that was administered study drug, regardless of causal attribution.
Change From Baseline in SDAI at Week 96
时间窗: Baseline, Week 96
The SDAI was the numerical sum of five outcome parameter: SJC and TJC, PGA and IGA, and level of hsCRP. The index was calculated using the following formula SDAI = TJC28 + SJC28 + PGA + IGA + CRP. Change in SDAI = SDAI at Week 96 - SDAI at Baseline. SDAI total score = 0-86. SDAI \<=3.3 indicates clinical remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity.
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 48
时间窗: Baseline, Week 48
The SDAI was the numerical sum of five outcome parameter: SJC and TJC, Patient Global Assessment of Disease Activity (PGA) and Investigator Global Assessment of Disease Activity (IGA), and level of hsCRP. The index was calculated using the following formula SDAI = TJC28 + SJC28 + PGA + IGA + CRP. Change in SDAI = SDAI at Week 48 - SDAI at Baseline. SDAI total score = 0-86. SDAI \<=3.3 indicates clinical remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high (or severe) disease activity. Here, n signifies the number of subjects evaluable at the specified time points.
Change From Baseline in Total TJC at Week 96
时间窗: Baseline, Week 96
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A smaller number indicated improvement.
Change From Baseline in SJC at Week 96
时间窗: Baseline, Week 96
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. Change in SJC = SJC at Week 96 - SJC at Baseline. A negative number indicated improvement.
Change From Baseline in Swollen Joint Count (SJC) at Week 48
时间窗: Baseline, Week 48
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A negative number indicated improvement.
Change From Baseline in Total Tender Joint Count (TJC) at Week 48
时间窗: Baseline, Week 48
An assessment of 66 joints for swelling and 68 joints for tenderness was made. Joints were assessed and classified as tender/not tender and swollen/not swollen by pressure and joint manipulation on physical examination. A smaller number indicated improvement. Here, 'n' represents the number of participants with a measure at specified time point.
次要结局
- Percentage of Participants With Remission (DAS28 <2.6 or SDAI </=3.3) at Weeks 48 and 96(Week 48, Week 96)
- Percentage of Participants With Disease-Modifying Antirheumatic Drugs (DMARDs)/Corticosteroid Dose Reductions and/or Discontinuation(Randomization of first participant to clinical cutoff date (19MAY2015) (approximately 29 months))
- Patient Global Visual Analog Score (VAS) at Specified Time Points(Baseline, Week 48, Week 96)
- Patient Pain VAS Score at Specified Time Points(Baseline, Week 48, Week 96)
- Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Specified Time Points(Baseline, Week 48, Week 96)