Randomized, Phase IV, Placebo-controlled, Comparative Study to Evaluate the Efficacy and Safety of Tapering Methotrexate (MTX) Dosage Versus Maintaining the Dosage in Patients With Severe Active Rheumatoid Arthritis (RA) Who Have Demonstrated an Inadequate Response (IR) to Prior Disease-modifying Anti-rheumatic Drugs (DMARDs) Treatment and Have Initiated RoActemra (RoActemra, TCZ) in Combination With MTX
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 427
- 主要终点
- Percentage of Participants Maintaining Previous Disease Activity (European League Against Rheumatism [EULAR] Response) From Week 24 (Time of Randomization) to Week 60
研究概览
简要总结
This randomized, placebo-controlled, double-blind study will compare the safety and efficacy of tapering methotrexate (MTX) versus maintaining MTX dosage in patients with severe active rheumatoid arthritis and an inadequate response to disease-modifying antirheumatic drugs (DMARDs) initiated on treatment with tocilizumab. Participants will receive tocilizumab 8 mg/kg intravenously every 4 weeks and MTX orally weekly throughout the study. At Week 24, participants achieving a good/moderate EULAR response will be randomized receiving the MTX Tapering arm or MTX Maintenance arm. Up to Week 56 participants will receive either tapering or stable dose MTX in combination with tocilizumab. From Week 56 to Week 72 participants will receive tocilizumab monotherapy.
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
- Double (Participant, Investigator)
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 patients, >/= 18 years of age
- •Active severe rheumatoid arthritis (DAS28 > 5.1) according to European League of Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria
- •Inadequate response to a trial of 2 DMARDs, including methotrexate, a trial being defined as 6 months with 2 months at standard dose; no previous treatment with a biologic agent such as a tumor necrosis factor (TNF) inhibitor
- •Oral corticosteroids must have been at a stable dose of </= 10 mg/day prednisolone or equivalent for at least 25 out of 28 days prior to start of treatment (Day 1)
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 rheumatoid arthritis
- •Functional class IV as defined by the ACR Classification of Functional Status in RA
- •Prior history of or current inflammatory joint disease other than RA
- •Previous treatment with tocilizumab
- •Previous treatment with any biologic drug (e.g. TNF inhibitor) that is used in the treatment of RA
- •Intraarticular or parenteral corticosteroids within 6 weeks prior to enrollment
- •Inadequate liver, bone marrow or hepatic function
- •Positive for hepatitis B, hepatitis C or HIV infection
- •Pregnant or breastfeeding women
- •Females of child-bearing potential who are not using reliable means of contraception
- •History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
- •Active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections
- •History of, or currently active, primary or secondary immunodeficiency
研究组 & 干预措施
Methotrexate (MTX) Tapering Dosage
At Week 0 participants will start open-label tocilizumab and open-label MTX for 24 weeks. At Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response will be randomized to the MTX Tapering group or MTX Maintenance group. In this arm participants will receive a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. Participants will also continue to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants will receive tocilizumab monotherapy.
干预措施: Tocilizumab (Drug)
Methotrexate (MTX) Tapering Dosage
At Week 0 participants will start open-label tocilizumab and open-label MTX for 24 weeks. At Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response will be randomized to the MTX Tapering group or MTX Maintenance group. In this arm participants will receive a double-blind MTX dose according to the MTX tapering scheme between Week 24 and Week 56. Participants will also continue to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants will receive tocilizumab monotherapy.
干预措施: Methotrexate (tapering dose) (Drug)
Methotrexate (MTX) Maintenance Dosage
At Week 0 participants will start open-label tocilizumab and open-label MTX for 24 weeks. At Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response will be randomized to the MTX Tapering group or MTX Maintenance group. In this arm participants will continue to be administered a stable dose of MTX in a double-blind fashion between Week 24 and Week 56. Participants will also continue to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants will receive tocilizumab monotherapy.
干预措施: Methotrexate (stable dose) (Drug)
Methotrexate (MTX) Maintenance Dosage
At Week 0 participants will start open-label tocilizumab and open-label MTX for 24 weeks. At Week 24, participants achieving a good/moderate European League Against Rheumatism (EULAR) disease response will be randomized to the MTX Tapering group or MTX Maintenance group. In this arm participants will continue to be administered a stable dose of MTX in a double-blind fashion between Week 24 and Week 56. Participants will also continue to receive open-label tocilizumab between Week 24 and Week 56. From Week 56 to Week 72 participants will receive tocilizumab monotherapy.
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Percentage of Participants Maintaining Previous Disease Activity (European League Against Rheumatism [EULAR] Response) From Week 24 (Time of Randomization) to Week 60
时间窗: From randomization to Week 60
Response was determined using EULAR criteria based upon (Disease Activity Score In 28 Joints) DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit. Participants with a score lesser than or equal to (\<=) 3.2 and reduction of greater than (\>) 1.2 points were assessed as having a 'good' response. Participants with a score \>3.2 with reduction of \>1.2 points, or a score \<=5.1 with reduction of \>0.6 to \<=1.2 points, were assessed as having a 'moderate' response. Participants with a score \>5.1 with reduction of \>0.6 to \<=1.2 points, or any score with reduction \<=0.6 points, were assessed as non-responders with response recorded as 'none.'
次要结局
- Percentage of Participants Who Achieve a Disease Activity Score In 28 Joints (DAS28) <= 3.2(Week 60, 72)
- Change From Baseline in Disease Activity Score In 28 Joints (DAS28) Score at Week 60(Randomization (Week 24), Week 60)
- Change From Baseline in Disease Activity Score In 28 Joints (DAS28) Score at Week 72(Randomization (Week 24), Week 72)
- Percentage of Participants Who Achieve Score of <=1 in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 60 and 72(Week 60, 72)
- Percentage of Participants Who Achieve DAS28 Remission (DAS28 < 2.6)(Week 60, 72)
- Percentage of Participants Who Achieve Simplified Disease Activity Index (SDAI) Remission (SDAI < 3.3) at Week 60 and 72(Randomization (Week 24), Week 60, 72)
- Percentage of Participants Who Achieve Change in Disease Activity Score (cDAS) >=1.2(Week 60, 72)
- Percentage of Participants Who Achieve Clinical Disease Activity Index (CDAI) Remission (CDAI < 2.8) at Week 60 and 72(Randomization (Week 24), Week 60, 72)
- Percentage of Participants With Improvement in Physical Function Using Health Assessment Questionnaire [HAQ] at Week 60 and 72(Randomization (Week 24), Week 60, 72)
- Percentage of Participants With Improvement in Physical Function Using Functional Assessment of Chronic Illness Therapy - Fatigue [FACIT-F] at Week 60 and 72(Randomization (Week 24), Week 60, 72)
- Percentage of Participants With Anemia(Week 0 up to Week 72)
- Change in Productivity and Regular Daily Activities Affected by Rheumatoid Arthritis Assessed Using the WPAI-SHP(Randomization (Week 24), Week 60, 72)
- Percentage of Participants With Improvement in Physical Function Using 12-item Short Form Health Survey [SF-12]) at Week 60 and 72(Randomization (Week 24), Week 60, 72)
- Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP)(Randomization (Week 24), Week 60, 72)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Week 0 up to Week 72)
- Percentage of Participants Able to Discontinue Methotrexate(Week 0 up to Week 60)
- Hours Actually Worked and Work Hours Missed Assessed Using the WPAI-SHP(Randomization (Week 24), Week 60, Week 72)