A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab in Rheumatoid Arthritis Patients Currently Receiving Treatment With Methotrexate
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Abbott
- 入组人数
- 619
- 试验地点
- 87
- 主要终点
- Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 24
研究概览
简要总结
The purpose of the study was to assess the safety, immunogenicity, and clinical efficacy of adalimumab compared with placebo (during double-blind phase) and to to evaluate the long-term safety and maintenance of efficacy following repeated administration of adalimumab (during open-label extension phase) in patients with persistently active rheumatoid arthritis who were receiving concurrent methotrexate therapy.
详细描述
This was a 10-year study which had an initial 52-week, double-blind, placebo-controlled phase followed by an open-label extension phase up to 9 years in duration. Data were analyzed for the double-blind phase using all patients who were randomized and received at least one dose of study drug through Week 52 and for all patients who received at least one dose of adalimumab during the 10-year study (the Intent-to-Treat [ITT] population).
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
- •Age 18 or older and in good health (Investigator discretion) with a recent stable medical history
- •Met American College of Rheumatology (ACR) criteria for diagnosis of active rheumatoid arthritis (RA) and had at both screening and baseline visits >=6 swollen joints and >=9 tender joints, despite a minimum of 3-months treatment with methotrexate (MTX). (Distal interphalangeal joints [DIPs] were not to be included in joint count for inclusion. The screening and baseline visits could be 3 to 28 days apart for patients not previously receiving disease-modifying anti-rheumatic drugs [DMARDs] other than MTX or 4 to 6 weeks for patients requiring a DMARD washout period.)
- •Insufficient efficacy with MTX 12.5 to 25 mg per week (10 mg per week if MTX intolerant).
- •If patient on a second-line treatment (DMARD) other than MTX, he/she had to discontinue it for at least 28 days before the baseline visit (the washout period).
- •Treatment with oral folic acid 1-3 mg/day or, if appropriate, up to 10 mg leucovorin per week.
- •Both rheumatoid factor positivity and a C-reactive protein value >=1 mg/dL, or at least one joint erosion on X-ray.
排除标准
- •Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study.
- •Female subject who was pregnant or breast-feeding or considering becoming pregnant.
- •Preceding treatment with any tumor necrosis factor (TNF) antagonist, including adalimumab.
- •Prior exposure to alkylating agents, such as chlorambucil or cyclophosphamide.
- •Intra-articular, intramuscular, or intravenous administration of corticosteroids within 4 weeks prior to the screening visit.
- •Subject was wheelchair bound or bedridden.
研究组 & 干预措施
DB adalimumab 20 mg ew
Subjects received 20 mg adalimumab subcutaneously (SC) once weekly (ew) and concomitant methotrexate (MTX) during the double-blind (DB) phase.
干预措施: Adalimumab (Biological)
DB adalimumab 40 mg eow
Subjects received 40 mg adalimumab subcutaneously (SC) every other week (eow) and concomitant methotrexate (MTX) during the double-blind (DB) phase. Subjects received placebo injections SC and concomitant MTX on the alternate weeks during the DB phase.
干预措施: Adalimumab (Biological)
DB placebo ew
Subjects received placebo subcutaneously (SC) once weekly (ew) and concomitant methotrexate (MTX) during the double-blind (DB) phase.
干预措施: Placebo (Drug)
DB adalimumab 20 mg ew/OL adalimumab 40 mg eow
Subjects received adalimumab 20 mg subcutaneously (SC) once weekly (ew) during the double-blind (DB) phase, then adalimumab 40 mg SC every other week (eow) during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).
干预措施: Adalimumab (Biological)
DB adalimumab 40 mg eow/OL adalimumab 40 mg eow
Subjects received adalimumab 40 mg subcutaneously (SC) every other week (eow) with placebo on alternate weeks during the double-blind (DB) phase, then adalimumab 40 mg SC eow during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).
干预措施: Adalimumab (Biological)
DB placebo ew/OL adalimumab 40 mg eow
Subjects received placebo subcutaneously (SC) once weekly (ew) during the double-blind phase, then adalimumab 40 mg SC every other week (eow) during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).
干预措施: Adalimumab (Biological)
结局指标
主要结局
Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 24
时间窗: Week 24
Patients were responders if they had: \>= 20% improvement in tender joint count; \>= 20% improvement in swollen joint count; and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
Change From Baseline in Modified Total Sharp X-ray Score at Week 52
时间窗: Baseline and Week 52
Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 52. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 \[normal\] to 398 \[maximal disease\]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.
Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 52
时间窗: Baseline and Week 52
Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from baseline in the disability index of the HAQ indicated improvement.
次要结局
- Number of Participants Meeting ACR20 Response Criteria at Week 52(Week 52)
- Change From Baseline in Modified Total Sharp X-ray Score at Week 24(Baseline and Week 24)
- Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 24(Baseline and Week 24)
- Maintenance of the Disability Index of the HAQ at Week 52 for Participants Who Were Responders at Week 12 or Week 24(Week 52)
- Maintenance of ACR20 Response at Week 52 for Participants Who Were ACR20 Responders at Week 24(Week 52)
- Number of Participants With a Continuous ACR70 Response for 6 Months During 52 Weeks of Treatment(Baseline through Week 52)
- Time to First Response According to ACR20 Criteria - Number of Participants Meeting ACR20 Criteria for the First Time at Each Time Point(Baseline through Week 52)
- Time to First Response According to ACR50 Criteria - Number of Participants Meeting ACR50 Criteria for the First Time at Each Time Point(Baseline through Week 52)
- Time to First Response According to ACR70 Criteria - Number of Participants Meeting ACR70 Criteria for the First Time at Each Time Point(Baseline through Week 52)
- Estimated Yearly Progression of Rheumatoid Arthritis(Baseline and Week 52)