A Phase II, Randomized, Parallel-group, Open-label, Multicenter Study to Evaluate the Effects of Rituximab on Immune Responses in Subjects With Active Rheumatoid Arthritis Receiving Background Methotrexate
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 103
- 试验地点
- 34
- 主要终点
- Percentage of Patients With a Positive Immune Response to Tetanus Toxoid Adsorbed Booster Vaccine
研究概览
简要总结
This was a Phase II, randomized, open-label, multicenter study designed to evaluate the immune response to vaccines after administration of 1000 mg of rituximab in subjects with active rheumatoid arthritis (RA) who were receiving background methotrexate (MTX).
详细描述
Patients were randomized to 2 groups in this study: Group A (active group) and Group B (control group). Patients with active rheumatic arthritis treated with rituximab in combination with methotrexate (Group A) were compared with patients treated with methotrexate alone (Group B).
Group A
Group A patients received rituximab 1000 mg intravenously (IV) on Days 3 and 17 of the 36 week treatment period.
At Day 1 and at Week 24, patients received an intradermal injection of 0.1 mL of C. albicans on the volar surface of the forearm. Forty-eight to 72 hours after each injection, patients were evaluated for a delayed-type hypersensitivity response by measuring the diameter of induration (palpable raised, hardened area of the forearm skin).
At Week 24, patients received a tetanus toxoid adsorbed booster vaccine (1 mg in 0.5 mL) intramuscular (IM) injection in the deltoid muscle. Serum levels of tetanus toxoid titers were obtained at Day 3 immediately prior to the first administration of rituximab, and immediately prior to and 4 weeks after administration of the tetanus toxoid adsorbed vaccine.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years.
- •Diagnosis of rheumatoid arthritis (RA) for at least 6 months.
- •Receiving treatment for RA on an outpatient basis.
- •Use of methotrexate (MTX) at a dose of 10-25 mg/wk (oral [PO] or subcutaneous [SC]) for at least 12 weeks prior to Day 1, with the dose stable during the last 4 weeks prior to Day 1 (first day of the treatment period).
- •If taking a background corticosteroid, use of the corticosteroid must be for at least 12 weeks prior to Day 1 at a stable dose during the last 4 weeks prior to Day
- •If taking one non-steroidal anti-inflammatory drug (NSAID), use of a stable dose for at least 2 weeks prior to Day 1.
排除标准
- •Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA; Sjogren's syndrome with RA is permitted.
研究组 & 干预措施
Methotrexate (Group B)
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
干预措施: 23-valent pneumococcal polysaccharide vaccine (Biological)
Methotrexate (Group B)
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
干预措施: Keyhole limpet hemocyanin (Biological)
Rituximab + methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
干预措施: Rituximab (Drug)
Rituximab + methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
干预措施: Methotrexate (Drug)
Rituximab + methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
干预措施: Methylprednisone (Drug)
Rituximab + methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
干预措施: C. albicans (Biological)
Rituximab + methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
干预措施: Tetanus toxoid adsorbed booster vaccine (Biological)
Rituximab + methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
干预措施: 23-valent pneumococcal polysaccharide vaccine (Biological)
Rituximab + methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
干预措施: Keyhole limpet hemocyanin (Biological)
Methotrexate (Group B)
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
干预措施: Methotrexate (Drug)
Methotrexate (Group B)
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
干预措施: C. albicans (Biological)
Methotrexate (Group B)
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
干预措施: Tetanus toxoid adsorbed booster vaccine (Biological)
结局指标
主要结局
Percentage of Patients With a Positive Immune Response to Tetanus Toxoid Adsorbed Booster Vaccine
时间窗: Week 24 to Week 28 for Group A and Day 1 to Week 4 for Group B
The immune response to tetanus toxoid adsorbed booster vaccine was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The tetanus antibody test was an ELISA that used tetanus toxoid as a capturing reagent and alkaline phosphatase-conjugated anti-human IgG (γ) for detection. For patients with pre-vaccination tetanus antibody titers \< 0.1 IU/mL, a positive immune response was defined as an antibody titer ≥ 0.2 IU/mL. For patients with pre-vaccination tetanus antibody titers ≥ 0.1 IU/mL, a positive immune response to the booster immunization was defined as a 4-fold increase in antibody titer.
次要结局
- Percentage of Patients Who Maintained a Positive Response to the C. Albicans Skin Test From Day 1 to Week 24 for Group A or From Day 1 to Week 12 for Group B(Day 1 to Week 24 for Group A and Day 1 to Week 12 for Group B)
- Serum Level of Anti-tetanus Antibody Measured Immediately Prior to and 4 Weeks After Administration of a Tetanus Toxoid Adsorbed Booster Vaccine(Week 24 to Week 28 for Group A and Day 1 to Week 4 for Group B)
- Percentage of Patients With a Positive Immune Response to Each of the 12 Anti-pneumococcal Antibody Serotypes in Response to the 23-valent Pneumococcal Polysaccharide Vaccine(Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B)
- Percentage of Patients With a Positive Immune Response to at Least 50% (≥ 6 of 12) of the 12 Anti-pneumococcal Antibody Serotypes in Response to the 23-valent Pneumococcal Polysaccharide Vaccine(Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B)
- Percentage of Patients With a Positive Immune Response to at Least k (for k = 1, 2, 3, 4, 5) of the 12 Anti-pneumococcal Antibody Serotypes in Response to the 23-valent Pneumococcal Polysaccharide Vaccine(Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B)
- Serum Level of Anti-pneumococcal Antibody Measured Immediately Prior to and 4 Weeks After Administration of a 23-valent Pneumococcal Polysaccharide Vaccine(Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B)
- Serum Level of Anti-keyhole Limpet Hemocyanin Antibody Measured Immediately Prior to and 4 Weeks After the First Administration of Keyhole Limpet Hemocyanin(Week 32 to Week 36 for Group A and Week 8 to Week 12 for Group B)
- Percentage of Patients in Group A With an Improvement of at Least 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Week 24(Week 24)
- Percentage of Patients With a 2-fold Increase in Tetanus Antibody Titers or With Tetanus Antibody Titers ≥ 0.2 IU/mL in Response to Tetanus Toxoid Adsorbed Booster Vaccine(Week 24 to Week 28 for Group A and Day 1 to Week 4 for Group B)