A Double-Blind, Randomized, Parallel-Arm, Multicenter Study to Determine the Dose Response of Methotrexate (MTX) in Combination Therapy With Adalimumab in Subjects With Early Rheumatoid Arthritis (CONCERTO)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 395
- 试验地点
- 68
- 主要终点
- Percentage of Participants With 28-Joint Disease Activity Score of C-reactive Protein (DAS28[CRP]) Low Disease Activity at Week 26
研究概览
简要总结
The purpose of this study is to determine the effects of different doses of methotrexate (MTX) when taken with adalimumab in subjects with early rheumatoid arthritis (RA).
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
- •Male and female subjects at least 18 years of age
- •Subject has a diagnosis of Rheumatoid Arthritis (RA) as defined by either the 1987-revised American College of Rheumatology (ACR) classification criteria or the new ACR/ European League Against Rheumatism (EULAR) diagnostic criteria for RA 2010 and has a disease duration of less than 1 year from diagnosis by a licensed health care provider
- •Subject must meet the following criteria:
- •Disease Activity Score of C-reactive Protein (DAS28[CRP]) ≥ 3.2 (at the Baseline visit only)
- •At least 6 swollen joints out of 66 assessed (at the Screening and Baseline visits)
- •At least 8 tender joints out of 68 assessed (at the Screening and Baseline visits)
- •C-reactive protein (CRP) ≥ 1.5 mg/dL (at the Screening visit only), or erythrocyte sedimentation rate (ESR) ≥ 28 mm/1h (at the Screening and Baseline visits)
- •Fulfill at least one of the following three criteria: Rheumatoid Factor (RF) positive, have at least 1 bony erosion, anti-cyclic citrullinated peptide (anti-CCP) antibody positive
- •Subject is judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during Screening
排除标准
- •Subject has previous exposure to any systemic biologic therapy including adalimumab
- •Subject has been previously treated with greater than 1 disease modifying antirheumatic drugs (DMARDs) or with methotrexate (MTX)
- •Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study)
- •Subject has chronic arthritis diagnosed before age 17 years
- •History of invasive infection (e.g., listeriosis and histoplasmosis), chronic or active Hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active tuberculosis (TB)
- •Hepatitis B virus: hepatitis B surface antigen (HBs Ag) positive (+) or detected sensitivity on the hepatitis B virus DNA (HBV DNA) polymerase chain reaction (PCR) qualitative test
- •Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline visit
- •Female subject who is pregnant or breast-feeding or considering becoming pregnant
研究组 & 干预措施
ADA + 2.5 mg MTX
2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks
干预措施: adalimumab (Biological)
ADA + 2.5 mg MTX
2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks
干预措施: methotrexate (Drug)
ADA + 5 mg MTX
5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks
干预措施: adalimumab (Biological)
ADA + 5 mg MTX
5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks
干预措施: methotrexate (Drug)
ADA + 10 mg MTX
10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks
干预措施: adalimumab (Biological)
ADA + 10 mg MTX
10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks
干预措施: methotrexate (Drug)
ADA + 20 mg MTX
MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
干预措施: adalimumab (Biological)
ADA + 20 mg MTX
MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
干预措施: methotrexate (Drug)
结局指标
主要结局
Percentage of Participants With 28-Joint Disease Activity Score of C-reactive Protein (DAS28[CRP]) Low Disease Activity at Week 26
时间窗: Week 26
Percentage of participants achieving low disease activity as defined by a clinical response (DAS28\[CRP\] \< 3.2). The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score \>5.1 indicates high disease activity, a DAS28 score \<3.2 indicates low disease activity, and a DAS28 score \<2.6 indicates clinical remission.
次要结局
- Percentage of Participants With American College of Rheumatology (ACR) 70 Criteria Response at Week 26(Baseline, Week 26)
- Percentage of Participants With American College of Rheumatology (ACR) 100 Criteria Response at Week 26(Baseline, Week 26)
- Percentage of Participants With DAS28(CRP) Remission at Week 26(Week 26)
- Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26(Baseline, Week 26)
- Percentage of Participants With American College of Rheumatology (ACR) 20 Criteria Response at Week 26(Baseline, Week 26)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 26(Baseline, Week 26)
- Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ -0.22 at Week 26(Baseline, Week 26)
- Percentage of Participants With No Radiographic Progression at Week 26(Baseline, Week 26)
- Percentage of Participants With American College of Rheumatology (ACR) 50 Criteria Response at Week 26(Baseline, Week 26)
- Percentage of Participants With American College of Rheumatology (ACR) 90 Criteria Response at Week 26(Baseline, Week 26)
- Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Week 26(Week 26)
- Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Week 26(Week 26)