Multicenter Comparative Randomised Double-blind Placebo-controlled Clinical Trial to Evaluate Efficacy and Safety of Acellbia® (JSC "BIOCAD") With Methotrexate in First Line of Biological Therapy of Patients With Active Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Biocad
- 入组人数
- 159
- 主要终点
- Percentage of patients who developed ACR20 response on 24 week of therapy
研究概览
简要总结
The mail goal of this study is to establish superiority in efficacy of Acellbia® applied in a dose of 600 mg (Day 1 and Day 15) in combination with methotrexate in patients with active RA seropositive previously untreated with biological therapy, compared to standard therapy with methotrexate.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent. Age from 18 to 80 years. Rheumatoid arthritis diagnosed at least 6 months before informed consent signing Presence of more than 8 swollen and more than 8 painful joints at screening. C-reactive protein 7 mg/l or more AND/OR erythrocyte sedimentation rate 28 mm/hour or more.
- •Antibodies to citrullinated cyclic peptide 20 U/ml or more AND/OR rheumatoid factor-IgM higher than upper normal limit.
- •Documented regular methotrexate intake for 12 weeks, stable dose from 10 to 25 mg/week during last 4 weeks before signing informed consent.
排除标准
- •Methotrexate intolerance. Felty's syndrome. Patient functional status - IV class according to ACR. Previous use of biologic drugs to treat rheumatoid arthritis, biologic drugs that deplete CD20-lymphocytes, azathioprine use in the last 28 days prior to informed consent signing, leflunomide use in the last 8 weeks prior to informed consent signing, sulphasalazine/hydroxyquinoline use in the last 28 days prior to informed consent signing, intraarticular use of corticosteroids in the last 4 weeks prior to informed consent signing, patient requires prednisolone (or analogues) in a dose more than 10 mg/day or dose is unstable during 4 weeks prior to informed consent signing, requirement in non-steroid antiinflammatory drugs if their dose was not stable during last 8 weeks prior to informed consent signing.
- •Patient has inflammatory joint disease otherwise than rheumatoid arthritis or systemic autoimmune diseases.
- •Full list of inclusion and exclusion criteria can be found in Study Protocol.
研究组 & 干预措施
Acellbia + methotrexate
106 patients of this group will receive methotrexate in combination with a drug Acellbia to be used at a dose of 600 mg as a slow intravenous infusion carried out on day 1 and day 15.
If a follow-up examination at 24 weeks or later (up to 48 weeks) reveals that the patient still has active arthritis (evaluation index DAS28-4 (ESR)> 2,6 points), the therapy with Acellbia is repeated by the same scheme - 2 infusion at a dose of 600 mg at intervals of 14 days.
干预措施: Acellbia (Biological)
Acellbia + methotrexate
106 patients of this group will receive methotrexate in combination with a drug Acellbia to be used at a dose of 600 mg as a slow intravenous infusion carried out on day 1 and day 15.
If a follow-up examination at 24 weeks or later (up to 48 weeks) reveals that the patient still has active arthritis (evaluation index DAS28-4 (ESR)> 2,6 points), the therapy with Acellbia is repeated by the same scheme - 2 infusion at a dose of 600 mg at intervals of 14 days.
干预措施: Methotrexate (Drug)
Placebo + methotrexate
53 patients of this group will receive methotrexate in combination with a placebo to be used as a slow intravenous infusion carried out on day 1 and day 15.
If a follow-up examination at 24 weeks or later (up to 48 weeks) reveals that the patient still has active arthritis (evaluation index DAS28-4 (ESR)> 2,6 points), the patient receives open therapy with Acellbia is initiated: 2 infusion at a dose of 600 mg at intervals of 14 days.
干预措施: Acellbia (Biological)
Placebo + methotrexate
53 patients of this group will receive methotrexate in combination with a placebo to be used as a slow intravenous infusion carried out on day 1 and day 15.
If a follow-up examination at 24 weeks or later (up to 48 weeks) reveals that the patient still has active arthritis (evaluation index DAS28-4 (ESR)> 2,6 points), the patient receives open therapy with Acellbia is initiated: 2 infusion at a dose of 600 mg at intervals of 14 days.
干预措施: Placebo (Drug)
Placebo + methotrexate
53 patients of this group will receive methotrexate in combination with a placebo to be used as a slow intravenous infusion carried out on day 1 and day 15.
If a follow-up examination at 24 weeks or later (up to 48 weeks) reveals that the patient still has active arthritis (evaluation index DAS28-4 (ESR)> 2,6 points), the patient receives open therapy with Acellbia is initiated: 2 infusion at a dose of 600 mg at intervals of 14 days.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Percentage of patients who developed ACR20 response on 24 week of therapy
时间窗: Week 24
The proportion of patients achieving at least a 20% improvement in ACR criteria at 24 weeks of therapy.
次要结局
- Percentage of patients with progression of disease according to modified Steinbrocker method of assessment after 52 weeks of treatment(Week 52)
- Frequency of AE 3-4 grade CTCAE 4.03(52 weeks)
- Percentage of patients who developed ACR20, ACR50 and ACR70 response on 16 week of therapy(Week 16)
- Change in average HAQ-DI score after 24 weeks of therapy(Week 24)
- Change in average score of joint spase narrowing according to modified Sharp method of assessment after 24 weeks of therapy(Week 24)
- Percentage of patients who developed ACR20, ACR50 and ACR70 response on 52 week of therapy(Week 52)
- Change in average HAQ-DI score after 52 weeks of therapy(Week 52)
- Percentage of patients who developed ACR50 and ACR70 response on 24 week of therapy(Week 24)
- Change in average DAS28-4 (ESR) score after 24 weeks of therapy(Week 24)
- Change in average score according to modified Sharp method of assessment after 24 weeks of therapy(Week 24)
- Change in average score of joint space narrowing according to modified Sharp method of assessment after 52 weeks of therapy(Week 52)
- Frequency of premature withdrawal due to AE/SAE(52 weeks)
- Change in average score of erosions according to modified Sharp method of assessment after 24 weeks of therapy(Week 24)
- Percentage of patients with progression of disease according to modified Steinbrocker method of assessment after 24 weeks of treatment(Week 24)
- Change in average DAS28-4 (ESR) score after 52 weeks of therapy(Week 52)
- Percentage of patients who have developed binding and neutralizing antibodies to rituximab on week 24 and week 52(Week 24, Week 52)
- Change in average score according to modified Sharp method of assessment after 52 weeks of therapy(Week 52)
- Change in average score of erosions according to modified Sharp method of assessment after 52 weeks of therapy(Week 52)
- Frequency and severity of AE/SAE(52 weeks)