U-ACT-EARLY: A Multi-center, Randomized, Double Blind, Placebo Controlled Study to Evaluate Remission in DMARD and Biological naïve Early Rheumatoid Arthritis (RA) Subjects Treated With Tocilizumab (TCZ) Plus Tight Control Methotrexate (MTX) , TCZ Monotherapy or Tight Control MTX Monotherapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 317
- 主要终点
- Percentage of Participants Achieving Sustained Remission Rate At Week 104
研究概览
简要总结
This randomized, double-blind, placebo-controlled study will compare the efficacy with regard to sustained remission and safety of tocilizumab and methotrexate, in combination or as monotherapy, in treatment-naïve patients with early rheumatoid arthritis. Patients will be randomized to receive either tocilizumab (8mg/kg iv every 4 weeks) plus weekly methotrexate (po in ascending doses), or tocilizumab (8mg/kg iv every 4 weeks) plus placebo, or methotrexate plus placebo. Anticipated time on study treatment is 2 years, and target sample size is 300.
详细描述
Multi-center, randomized, double-blind, placebo-controlled (double placebo) three-arm parallel group, comparative study. Patients were randomized in a 1:1:1 ratio to one of the following treatments:
- TCZ 8 milligram (mg)/kilogram (kg) + MTX (Group I: TCZ+MTX)
- TCZ 8 mg/kg + placeboMTX (Group II: TCZ+placebo)
- MTX + placeboTCZ (Group III: MTX+placebo)
Randomization was stratified by participating center and baseline Disease Activity Score, scoring 28 joints (DAS28) level (<5.1 vs. ≥5.1). Patients were evaluated every 4 weeks and at each visit a decision on dosage changes was made based on efficacy parameters (DAS28) and occurrence of adverse events (AEs). Patients received MTX/placeboMTX in climbing dosages. Hydroxychloroquine (HCQ) was added when remission was not reached with the maximum tolerable dosage (MTD) of MTX/placeboMTX. If after 12 additional weeks remission was not reached, HCQ was stopped and replaced by standard of care therapy (in Group I) or placebo therapy was replaced by the corresponding verum resulting in TCZ+MTX combination therapy (in Groups II and III). In case remission was reached, MTX/placeboMTX and TCZ/placeboTCZ had to be decreased. Patients were followed for a maximum of 24 months
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
- •early rheumatoid arthritis (disease symptoms <1 year) according to ACR criteria
- •disease activity DAS28 >2.6
- •body weight </=110kg, BMI </=36
排除标准
- •rheumatic autoimmune disease other than RA
- •current inflammatory joint disease other than RA
- •previous treatment with any DMARD or biologic drug used in the treatment of RA
- •intra-articular, parenteral or oral glucocorticoids used for the arthritis
研究组 & 干预措施
Tocilizumab + Methotrexate
Participants will receive intravenous (IV) TCZ 8 mg/kg every four weeks for a maximum of 26 infusions + oral capsules of MTX 10-30 mg/week in climbing dosages of 5 mg starting at 10 mg up till a maximum dosage of 30 mg/week. The weekly dose of MTX will be taken on one particular day of the week.
干预措施: methotrexate (Drug)
Tocilizumab + Methotrexate
Participants will receive intravenous (IV) TCZ 8 mg/kg every four weeks for a maximum of 26 infusions + oral capsules of MTX 10-30 mg/week in climbing dosages of 5 mg starting at 10 mg up till a maximum dosage of 30 mg/week. The weekly dose of MTX will be taken on one particular day of the week.
干预措施: tocilizumab [RoActemra/Actemra] (Drug)
Tocilizumab + Placebo Methotrexate
Participants will receive IV TCZ 8 mg/kg every four weeks for a maximum of 26 infusions + weekly oral matching placebo MTX capsules in climbing dosages. The weekly dose of placebo MTX will be taken on one particular day of the week.
干预措施: placebo MTX (Drug)
Tocilizumab + Placebo Methotrexate
Participants will receive IV TCZ 8 mg/kg every four weeks for a maximum of 26 infusions + weekly oral matching placebo MTX capsules in climbing dosages. The weekly dose of placebo MTX will be taken on one particular day of the week.
干预措施: tocilizumab [RoActemra/Actemra] (Drug)
Methotrexate + Placebo Tocilizumab
Participants will receive weekly oral MTX in climbing dosages of 5 mg starting at 10 mg up till a maximum dosage of 30 mg/week + matching placebo TCZ IV 8 mg/kg every four week for a maximum of 26 infusions. The weekly dose of MTX will be taken on one particular day of the week.
干预措施: methotrexate (Drug)
Methotrexate + Placebo Tocilizumab
Participants will receive weekly oral MTX in climbing dosages of 5 mg starting at 10 mg up till a maximum dosage of 30 mg/week + matching placebo TCZ IV 8 mg/kg every four week for a maximum of 26 infusions. The weekly dose of MTX will be taken on one particular day of the week.
干预措施: placebo TCZ (Drug)
结局指标
主要结局
Percentage of Participants Achieving Sustained Remission Rate At Week 104
时间窗: Week 104
Sustained remission rate (SRR) is defined as Disease Activity Score 28 (DAS28) \<2.6 during ≥ 23 weeks and no more than 4 swollen joints (28 joint count) due to RA at Week 24 of remission, with the exception of up to 2 in-between DAS28 values which could be between 2.6 and 3.2. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores indicate worsening. DAS28 \<2.6 equals (=) remission.
次要结局
- Median Time to First Disease Activity Score 28 Remission(Up to Week 104)
- Mean Duration of First Disease Activity Score 28 Remission(Up to Week 104)
- Percentage of Participants With Cumulative Remission Rate at Weeks 12, 24, 52, and 104(Weeks 12, 24, 52, and 104)
- Absolute Change From Baseline in Disease Activity Score 28 at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52, and 104)
- Median Time to First Sustained Remission(Up to Week 104)
- Mean Duration of First Sustained Remission(Up to Week 104)
- Number of Participants Achieving Disease Activity Score 28 Remission at Weeks 12, 24, 52, and 104(Weeks 12, 24, 52, and 104)
- Percentage of Participants With American College of Rheumatology 70 Response Rate at Weeks 12, 24, 52 and 104(Weeks 12, 24, 52 and 104)
- Percentage of Participants With American College of Rheumatology 90 Response Rate at Weeks 12, 24, 52 and 104(Weeks 12, 24, 52 and 104)
- Mean Percent Change From Baseline in Pain Visual Analog Scale at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52, and 104)
- Number of Participants With Change in The Therapy Strategy During The Study(From Baseline to Week 104)
- Median Change From Baseline in Clinical Disease Activity Index Score at Weeks 24, 52, and 104(From Baseline (Week 0) to Weeks 24, 52, and 104)
- Mean Percent Change From Baseline in The Physician Health Visual Analog Scale at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52, and 104)
- Percentage of Participants Who Withdraw Due to Lack of Sufficient Therapeutic Response(Up to Week 104)
- Mean Change From Baseline in The EuroQol Score of Quality of Life at Weeks 12, 24, 52 and 104(From Baseline (Week 0) to Weeks 12, 24, 52 and 104)
- Mean Change From Baseline in Patient Pain Visual Analog Scale Score of Quality of Life at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52 and 104)
- Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Score of Quality of Life at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52 and 104)
- Median Change From Baseline in Simplified Disease Activity Index Scores at Weeks 24, 52, and 104(From Baseline (Week 0) to Weeks 24, 52, and 104)
- Median Time to First European League Against Rheumatism Response(Up to Week 104)
- Mean Percent Change From Baseline in the Swollen Joint Count (SJC) at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52, and 104)
- Mean Percent Change From Baseline in Patient Health Visual Analog Scale at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52, and 104)
- Mean Change From Baseline in The Dutch Consensus Health Assessment Questionnaire of Quality of Life at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52 and 104)
- Mean Change From Baseline in Physician Global Health Visual Analog Scale Score of Quality of Life at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52 and 104)
- Number of Participants With Clinically Significant Laboratory Values at Week 12(Week 12)
- Number of Participants With Good European League Against Rheumatism Response Rate at Weeks 24, 52, and 104(Weeks 24, 52, and 104)
- Mean Percent Change From Baseline in the Tender Joint Count (TJC) at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52, and 104)
- Mean Change From Baseline in Patient Global Health Visual Analog Scale Score of Quality of Life at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52 and 104)
- Mean Change From Baseline in Modified Sharp/Van Der Heijde Score at Weeks 52 and 104(From Baseline (Week 0) to Weeks 52 and 104)
- Mean Change From Baseline in The IPQ-R Score of Quality of Life at Week 24(From Baseline (Week 0) to Week 24)
- Number of Participants With Any Adverse Events, Any Serious Adverse Events, and Adverse Events Leading to Discontinuation(Up to Week 104)
- Percentage of Participants With American College of Rheumatology 20 Response Rate at Weeks 12, 24, 52 and 104(Weeks 12, 24, 52 and 104)
- Percentage of Participants With American College of Rheumatology 50 Response Rate at Weeks 12, 24, 52 and 104(Weeks 12, 24, 52 and 104)
- Mean Percent Change From Baseline in CRP at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52, and 104)
- Mean Change From Baseline in The IPQ-R Score of Quality of Life at Week 52(From Baseline (Week 0) to Week 52)
- Number of Participants With Clinically Significant Laboratory Values at Week 24(Week 24)
- Mean Change From Baseline in 36-Item Short Form Health Survey of Quality of Life at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52 and 104)
- Mean Change From Baseline in Patient General Wellbeing Visual Analog Scale Score of Quality of Life at Weeks 12, 24, 52, and 104(From Baseline (Week 0) to Weeks 12, 24, 52 and 104)
- Mean Change From Baseline in The Revised Illness Perception Questionnaire (IPQ-R) Score of Quality of Life at Week 12(From Baseline (Week 0) to Week 12)
- Mean Change From Baseline in The IPQ-R Score of Quality of Life at Week 104(From Baseline (Week 0) to Week 104)
- Number of Participants With Clinically Significant Laboratory Values at Week 52(Week 52)
- Number of Participants With Clinically Significant Laboratory Values at Week 104(Week 104)