TOSCARA: An Open-label, Single Arm Study to Evaluate the Efficacy, Safety and Tolerability of Tocilizumab (TCZ) Subcutaneous in TCZ-naïve Patients With Active Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 57
- 主要终点
- Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Per Protocol Set (PPS)
研究概览
简要总结
This open-label, single-arm study will evaluate the efficacy, safety and tolerability of subcutaneously administered tocilizumab in monotherapy and/or in combination with methotrexate and other non-biologic disease modifying anti-rheumatic drug (DMARDs) in participants with active rheumatoid arthritis (RA) who are naïve to tocilizumab. Participants will receive tocilizumab 162 milligram (mg) subcutaneously weekly for 24 weeks. Participants who complete the core study achieving at least a moderate European League Against Rheumatism (EULAR) response at Week 24 may enter the extension phase and receive for a further 28 weeks at the most.
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
- •Active moderate to severe rheumatoid arthritis according to the revised (1987) American College of Rheumatology (ACR) criteria or EULAR/ACR (2010) criteria
- •Inadequate response or intolerant to previous therapy with two or more non-biologic disease-modifying anti-rheumatic drugs (DMARDs), one of which is methotrexate, administered in an optimal way during at least 3 months; eligible participants may also be inadequate responders to a maximum of one biologic DMARD
- •Oral corticosteroids (</= 10 milligram per day (mg/day) prednisolone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to the recommended dose) are permitted if on stable dose regimen for >/= 4 weeks prior to baseline
- •Permitted DMARDs are allowed if at stable dose for at least 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 reliable means of contraception as defined by protocol
排除标准
- •Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline or during long term extension (LTE) period
- •Rheumatic autoimmune disease other than rheumatoid arthritis
- •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 (intravenous or subcutaneous) 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
- •Intraarticular 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 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 or hepatitis C
- •Primary or secondary immunodeficiency (history of or currently active)
- •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
Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the long term extension (LTE) period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.
干预措施: tocilizumab (Drug)
结局指标
主要结局
Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Per Protocol Set (PPS)
时间窗: From baseline to Week 24
The DAS28 score is a measure of the participant's disease activity calculated using the TJC28, SJC28, PGA VAS with 0=no disease activity to 100=maximum disease activity displayed on the 100-mm horizontal VAS and acute phase reactant (ESR or CRP) for a total possible score of 0 to 10. For this study ESR was used to calculate the DAS28 score. The index is calculated using the following formula: DAS28 = (0.56\*√\[TJC28\]) + (0.28\*√\[SJC28\]) + (0.70\*ln\[ESR\]) + (0.014\*VAS). Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.
Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Full Analysis Set (FAS)
时间窗: From baseline to Week 24
The DAS28 score is a measure of the participant's disease activity calculated using the tender joint count of 28 joints (TJC28), swollen joint count of 28 joints (SJC28), patient's global assessment of disease activity visual analog scale (PGA VAS) with 0=no disease activity to 100=maximum disease activity displayed on the 100-millimeter (mm) horizontal VAS and acute phase reactant (erythrocyte sedimentation rate \[ESR\] or C-reactive protein \[CRP\]) for a total possible score of 0 to 10. For this study ESR was used to calculate the DAS28 score. The index is calculated using the following formula: DAS28 = (0.56\*√\[TJC28\]) + (0.28\*√\[SJC28\]) + (0.70\*ln\[ESR\]) + (0.014\*VAS). Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.
次要结局
- Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores(From Baseline to Week 2, Week 24, and Week 52)
- Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity(Baseline to Week 2, Week 24 and Week 52)
- Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity(From Baseline to Week 2, Week 24 and Week 52)
- Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity(From Baseline to Week 2, Week 24 and Week 52)
- Percentage of Participants Achieving a Clinically Significant Improvement in DAS28(From Baseline to Week 2, Week 24 and Week 52)
- Change From Baseline in Physician's Global Assessment of Disease Activity VAS(From Baseline to Week 2, Week 24 and Week 52)
- Change From Baseline in Patient's Global Assessment of Disease Activity VAS(From Baseline to Week 2, Week 24 and Week 52)
- Change From Baseline in Patient's Assessment of Pain VAS(From Baseline to Week 2 and Week 24)
- Acute Phase Reactants: Change From Baseline in CRP(From Baseline to Week 2, Week 24 and Week 52)
- Acute Phase Reactants: Change From Baseline in ESR(From Baseline to Week 2, Week 24 and Week 52)
- Percentage of Participants With Responses According to European League Against Rheumatism (EULAR ) Criteria(From Baseline to Week 2, Week 24)
- Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI)(From Baseline to Week 2, Week 24 and Week 52)
- Change in Total Tender/Swollen Joint Counts (TJC/SJC)(From Baseline to Week 2, Week 24 and Week 52)
- Percentage of Participants With Corticosteroid Dose Reduction/Discontinuation(Up to Week 52)
- Change From Baseline in Patient Fatigue VAS(From Baseline to Week 2, Week 24 and Week 52)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)(From Baseline to Week 2, Week 24 and Week 52)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)(From Baseline to Week 2, Week 24 and Week 52)
- Change From Baseline in Pittsburgh Sleep Quality Index (PSQI)(From Baseline to Week 4, Week 24 and Week 52)
- Change From Baseline in Patient Quality of Sleep VAS(From Baseline to Week 2, Week 24 and Week 52)
- Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF)(From Baseline to Week 4, Week 24 and Week 52)
- Change From Baseline in Patient Satisfaction VAS(From Baseline to Week 2, Week 24 and Week 52)
- Change From Baseline in Work Instability Scale for Rheumatoid Arthritis (RA-WIS)(From Baseline to Week 24)
- Treatment Satisfaction Questionnaire for Medication (TSQM ) Scores(Week 24)
- Safety: Percentage of Participants With Adverse Events(Up to 52 weeks)
- Safety: Percentage of Participants With Anti-tocilizumab Antibodies(Baseline, Week 24)