A Randomized, Parallel-group, Open-label, Multicenter Study to Evaluate the Effects of Tocilizumab on Vaccination in Subjects With Active Rheumatoid Arthritis Receiving Background Methotrexate
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 91
- 主要终点
- Percentage of Participants Who Responded to ≥ 6 of 12 Anti-pneumococcal Antibody Serotypes
研究概览
简要总结
This randomized, parallel-group, open-label study will evaluate the effect of Actemra (tocilizumab) on vaccination in patients with active rheumatoid arthritis who have an inadequate response to methotrexate and who have had an inadequate clinical response or were intolerant to treatment with one or more anti-tumor necrosis factor (anti-TNF) therapies.
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
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients, ≥ 18 to < 65 years of age
- •Rheumatoid Arthritis (RA) of > 6 months duration at baseline (American College of Rheumatology criteria)
- •Willing to receive immunization with pneumococcal polysaccharide and tetanus toxoid adsorbed vaccines
- •Previous immunization with pneumococcal polysaccharide must have occurred ≥ 3 years of baseline, with tetanus containing vaccine ≥ 5 years
- •Methotrexate therapy for at least 8 weeks prior to baseline at stable dose of 7.5-25 mg/week (oral or parenteral)
- •Other disease-modifying antirheumatic drugs (DMARDs) must be withdrawn before baseline
- •Oral corticosteroids must be at stable dose of < 10 mg/day prednisone or equivalent
- •Body weight ≤ 150 kg at screening
排除标准
- •Major surgery (including joint surgery) within 12 weeks prior to baseline or planned major surgery within 8 weeks after baseline
- •History of or current inflammatory joint disease or rheumatic autoimmune disease other than RA
- •Pre-existing central nervous system demyelinating or seizure disorders
- •Active current or history of recurrent bacterial, viral fungal, mycobacterial and other infections
- •Any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks prior to baseline or oral antibiotics within 2 weeks prior to baseline
- •Active tuberculosis requiring treatment within 3 years prior to baseline
- •Primary or secondary immunodeficiency (history or currently active)
- •Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
- •Previous treatment with RoActemra/Actemra
研究组 & 干预措施
Methotrexate
Participants continued to receive their standard dose of methotrexate up to Week 8. From Week 8 participants also received 8 mg/kg tocilizumab intravenously every 4 weeks until Week 20. At Week 3 participants received both pneumococcal and tetanus toxoid vaccinations.
干预措施: tocilizumab (Biological)
Methotrexate
Participants continued to receive their standard dose of methotrexate up to Week 8. From Week 8 participants also received 8 mg/kg tocilizumab intravenously every 4 weeks until Week 20. At Week 3 participants received both pneumococcal and tetanus toxoid vaccinations.
干预措施: methotrexate (Drug)
Methotrexate
Participants continued to receive their standard dose of methotrexate up to Week 8. From Week 8 participants also received 8 mg/kg tocilizumab intravenously every 4 weeks until Week 20. At Week 3 participants received both pneumococcal and tetanus toxoid vaccinations.
干预措施: 23-Valent Pneumococcal Polysaccharide Vaccine (Biological)
Methotrexate
Participants continued to receive their standard dose of methotrexate up to Week 8. From Week 8 participants also received 8 mg/kg tocilizumab intravenously every 4 weeks until Week 20. At Week 3 participants received both pneumococcal and tetanus toxoid vaccinations.
干预措施: Tetanus Toxoid Adsorbed Vaccine (Biological)
Tocilizumab + Methotrexate
Participants received 8 mg/kg tocilizumab intravenously at Baseline (Day 1) and every 4 weeks up to Week 20, in addition to their standard dose of methotrexate. At Week 3 participants received both pneumococcal and tetanus toxoid vaccinations.
干预措施: tocilizumab (Biological)
Tocilizumab + Methotrexate
Participants received 8 mg/kg tocilizumab intravenously at Baseline (Day 1) and every 4 weeks up to Week 20, in addition to their standard dose of methotrexate. At Week 3 participants received both pneumococcal and tetanus toxoid vaccinations.
干预措施: methotrexate (Drug)
Tocilizumab + Methotrexate
Participants received 8 mg/kg tocilizumab intravenously at Baseline (Day 1) and every 4 weeks up to Week 20, in addition to their standard dose of methotrexate. At Week 3 participants received both pneumococcal and tetanus toxoid vaccinations.
干预措施: 23-Valent Pneumococcal Polysaccharide Vaccine (Biological)
Tocilizumab + Methotrexate
Participants received 8 mg/kg tocilizumab intravenously at Baseline (Day 1) and every 4 weeks up to Week 20, in addition to their standard dose of methotrexate. At Week 3 participants received both pneumococcal and tetanus toxoid vaccinations.
干预措施: Tetanus Toxoid Adsorbed Vaccine (Biological)
结局指标
主要结局
Percentage of Participants Who Responded to ≥ 6 of 12 Anti-pneumococcal Antibody Serotypes
时间窗: Baseline (Week 3) and Week 8 (5 weeks post-vaccination)
Serum levels of antibody to pneumococcal vaccine were drawn 5 weeks after vaccination with 23-valent pneumococcal polysaccharide vaccine to assess humoral immune response. A positive response to the pneumococcal vaccine was defined as a 2-fold increase in serum antibody titers from Baseline or an increase of \> 1 mg/L from Baseline levels. The 12 serotypes evaluated were pneumococcal serotypes 1, 3, 4, 6B, 8, 9N, 12F, 14, 19F, 23F, 7F, and 18C.
次要结局
- Percentage of Participants Who Responded to Combinations of 12 Anti-Pneumococcal Antibody Serotypes(Baseline (Week 3) and Week 8 (5 weeks post-vaccination))
- Percentage of Participants With a Positive Response to Tetanus Toxoid Vaccination(Baseline (Week 3) and Week 8 (5 weeks post-vaccination))
- Change From Baseline in Levels of Anti-pneumococcal Antibody 5 Weeks After Vaccination(Baseline (Week 3) and Week 8 (5 weeks post-vaccination))
- Change From Baseline in Levels of Anti-tetanus Antibody 5 Weeks After Vaccination(Baseline (Week 3) and Week 8 (5 weeks post-vaccination))
- Percentage of Participants Who Responded to Each of the 12 Anti-Pneumococcal Antibody Serotypes(Baseline (Week 3) and Week 8 (5 weeks post-vaccination))
- Number of Participants With Adverse Events Through Week 8(8 weeks)