Tocilizumab SC in Patients With Active Rheumatoid Arthritis and Inadequate Response to DMARDs. A Single-Arm, Open-Label Study to Evaluate Safety, Tolerability and Efficacy. In a Subgroup of Patients Inflammation Will Be Measured by Ultrasound.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 133
- 试验地点
- 27
- 主要终点
- Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12
研究概览
简要总结
This Phase IIIb, open-label, single-arm study will evaluate the safety, efficacy, and tolerability of SC tocilizumab (RoActemra/Actemra) in monotherapy or in combination with methotrexate or other non-biologic DMARDs in participants with active RA who are naive to tocilizumab. Participants will receive tocilizumab 162 milligrams (mg) subcutaneously weekly (QW) for 24 weeks.
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
- •Active RA according to the revised ACR (1987) criteria or EULAR/ACR (2010) criteria
- •Moderate to severe RA with a DAS28-ESR score >3.2 points
- •Inadequate response and/or intolerance to MTX or other non-biologic DMARDs and/or where MTX or other non-biologic DMARDs are inappropriate
- •Oral corticosteroids (less than or equal to [</=] 10 mg per day prednisolone or equivalent) and nonsteroidal anti-inflammatory drugs (NSAIDs) permitted if on stable dose regimen for greater than or equal to [>/=] 4 weeks prior to baseline
- •Permitted non-biologic DMARDs allowed if at stable dose for >/=4 weeks prior to baseline
- •Receiving treatment on an outpatient basis, not including tocilizumab
- •Agreement to use reliable means of contraception as defined by protocol, among females of childbearing potential and males with female partners of childbearing potential
排除标准
- •Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline
- •Rheumatic autoimmune disease other than RA
- •Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
- •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 or any other biologic DMARDs 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
- •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 concomitant disease or disorder
- •Known active current or history of recurrent infection
- •Any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening
- •Active tuberculosis requiring treatment within the previous 3 years
- •Positive for hepatitis B or hepatitis C
- •History of or current active primary or secondary immunodeficiency
- •Pregnant or lactating women
- •Neuropathies or other conditions that might interfere with pain evaluation
- •Inadequate hematologic, renal, or liver function
研究组 & 干预措施
Tocilizumab Alone or Combined with Methotrexate or Other DMARD
All participants will receive tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs, irrespective of body weight, for 24 weeks.
干预措施: Tocilizumab (Drug)
Tocilizumab Alone or Combined with Methotrexate or Other DMARD
All participants will receive tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs, irrespective of body weight, for 24 weeks.
干预措施: Methotrexate (Drug)
Tocilizumab Alone or Combined with Methotrexate or Other DMARD
All participants will receive tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs, irrespective of body weight, for 24 weeks.
干预措施: Non-Biologic DMARDs (Drug)
结局指标
主要结局
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12
时间窗: Baseline, Week 12
CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA disease activity.
次要结局
- Change From Baseline in SJC(Baseline and Weeks 2, 4, 8, 12, 16, 20, 24)
- Number of Participants With Neutralizing Anti-Tocilizumab Antibodies(Baseline to FU Week 8 (up to 32 weeks overall))
- Compliance With Treatment According to Percentage of Injections Administered(Baseline up to Week 24)
- Change From Baseline in TJC(Baseline and Weeks 2, 4, 8, 12, 16, 20, 24)
- Soluble Interleukin-6 Receptor (sIL-6R) Concentration(Predose (30 minutes) at baseline; Weeks 12, 24; and FU Week 8 (up to 32 weeks overall))
- Change From Baseline in Patient Global Assessment of RA-Related Pain According to VAS(Baseline and Weeks 2, 4, 8, 12, 16, 20, 24)
- Change From Baseline in Disease Activity Score 28 (DAS28)-Erythrocyte Sedimentation Rate (ESR) Score(Baseline and Weeks 2, 4, 8, 12, 16, 20, 24)
- Change From Baseline in Simplified Disease Activity Index (SDAI)(Baseline and Weeks 2, 4, 8, 12, 16, 20, 24)
- Percentage of Participants With At Least One Adverse Event Leading to Dosage Modification(Baseline up to Week 24)
- Tocilizumab Concentration(Predose (30 minutes) at baseline; Weeks 12, 24; and FU Week 8 (up to 32 weeks overall))
- Change From Baseline in Patient Global Assessment of Disease Activity According to VAS(Baseline and Weeks 2, 4, 8, 12, 16, 20, 24)
- Percentage of Participants With American College of Rheumatology (ACR) Response(Weeks 2, 4, 8, 12, 16, 20, 24)
- Percentage of Participants With European League Against Rheumatism (EULAR) Response(Weeks 2, 4, 8, 12, 16, 20, 24)
- Change From Baseline in CDAI at Weeks 2, 4, 8, 16, 20, and 24(Baseline and Weeks 2, 4, 8, 16, 20, 24)
- Change From Baseline in HAQ-DI Score(Baseline and Weeks 2, 4, 8, 12, 16, 20, 24)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score(Baseline and Weeks 2, 4, 8, 12, 16, 20, 24)