A Multi-center Randomized, Phase 2/3, Double-blind, Parallel-group, Placebo-controlled Study to Assess the Safety and Efficacy of Adalimumab Administered as Subcutaneous Injections in Adult Chinese Rheumatoid Arthritis Subjects Treated With Methotrexate
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Abbott
- 入组人数
- 302
- 试验地点
- 14
- 主要终点
- Number of Participants With American College of Rheumatology (ACR)20 at Week 12 of the Double-Blind Period
研究概览
简要总结
A study to assess the safety and efficacy of adalimumab administered as a subcutaneous injection in adult Chinese subjects with rheumatoid arthritis and treated with methotrexate
详细描述
This was a multi-center, Phase 2/3, randomized, double-blind (DB), parallel group, placebo controlled, safety and efficacy study in adult Chinese RA subjects. The duration of the study was approximately 116 weeks. This included a 4-week (28 days) Screening period, a 12-week Double-Blind (DB) period, a 90-week Open-Label (OL) Period, and a 10-week (70 days) Follow-up period. The 70-day Safety Follow-up period was initiated after the last dose of study medication.
During the DB period, 302 Chinese subjects with RA and concomitantly treated with MTX were enrolled at 11 clinical sites located throughout China. Subjects were randomly assigned to one of the three treatment groups in a 2:2:1 ratio: 80 mg adalimumab, 40 mg adalimumab, or placebo. From Week 0 to Week 10, subjects received blinded study drug. Subjects who successfully participated and completed Week 12 of the DB portion of the study participated in the OL period. All subjects in the OL period received adalimumab 40 mg. Throughout the study, the study drug was administered subcutaneously (SC) every other week (eow).
Subjects that completed the Week 24 visit, prior to the approval of Protocol Amendment 1, had 70 days from the last dose of study drug to re-enter the study. The Investigator confirmed that the subject did not develop any of the exclusion criteria and completed the procedures defined by the OL Screening visit.
Results through Week 24 of this study were presented in the regulatory dossier for the marketing authorization application of Humira in China, fulfilling the requirement for clinical data in Chinese patients. However, in order to continue to provide treatment to patients who responded well to adalimumab, subjects had the option to continue in the OL extension of this study until Week 92.
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, Investigator, Outcomes Assessor)
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
- •Met ACR criteria for diagnosis of active rheumatoid arthritis (RA) and have had at both the Screening visit and Week 0 visit at least four swollen joints (out of 66 assessed) and at least six tender joints(out of 68 assessed)
- •Subjects must have failed prior treatment with one or more disease-modifying antirheumatic drugs (DMARDs)
- •DMARDs (other than methotrexate [MTX]) must have been discontinued for >= 28 days or at least 5 half-lives, whichever is greater, before the Week 0 visit
- •Traditional Chinese Medicines must have been discontinued for >= 28 days before the Week 0 visit
- •Subjects must have received at least three months of treatment with MTX (minimum 7.5 mg/week) and remained on a stable dose of MTX for >= 28 days prior to the Screening visit
- •Glucocorticoids equivalent to <= 10 mg of prednisone and prednisone equivalent must have remained unchanged for at least 28 days prior to the Week 0 visit
- •Must have been able and willing to give written informed consent and to comply with the requirements of this study protocol
排除标准
- •A history of, or current, acute inflammatory joint disease of different origin (e.g., mixed connective tissue disease, seronegative spondyloarthropathy, psoriatic arthritis, Reiter's syndrome, systemic lupus erythematosus, fibromyalgia or any arthritide with onset prior to age 16 years
- •Wheelchair-bound or bedridden
- •Joint surgery involving joints to be assessed within this study, within two months prior to the Screening visit
- •Intra-articular, intramuscular or intravenous administration of corticosteroids within 28 days prior to the Screening visit
- •Prior treatment with any TNF antagonist, including adalimumab
- •Subject considered by the investigator, for any reason, to be an unsuitable candidate
- •Female subject who is pregnant or breast-feeding or considering becoming pregnant
结局指标
主要结局
Number of Participants With American College of Rheumatology (ACR)20 at Week 12 of the Double-Blind Period
时间窗: Week 12
American College of Rheumatology (ACR) criteria improvement consisting of 20% (ACR20) reduction in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) physician's global assessment of disease activity, 2) subject's assessment of disease activity, 3) subject's assessment of pain, 4) subject's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit. Week 12 = end of Double-Blind period.
次要结局
- Number of Participants Achieving American College of Rheumatology (ACR)20 Response Through Week 92 of Open-Label Period(Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92)
- Number of Participants Achieving American College of Rheumatology (ACR)50/70 at Week 12 of the Double-Blind Period(Week 12)
- Number of Participants Achieving American College of Rheumatology (ACR)50 Response Through Week 92 of Open-Label Period(Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92)
- Number of Participants Achieving American College of Rheumatology (ACR)70 Response Through Week 92 of Open-Label Period(Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92)
- Mean Change in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12 of the Double-Blind Period(Baseline, Week 12)
- Mean Change in Tender Joint Count (TJC) Through Week 92 of the Open-Label Period(Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92)
- Mean Change in Swollen Joint Count (SJC) Through Week 92 of the Open-Label Period(Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92)
- Mean Change in Visual Analog Scale (VAS) Score at Week 12 of the Double-Blind Period(Baseline, Week 12)
- Mean Change in Physician's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period(Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92)
- Mean Change in Patient's Assessment of Pain (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period(Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92)
- Mean Change in Patient's Global Assessment of Disease Activity (Visual Analog Scale [VAS]) Through Week 92 of the Open-Label Period(Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92)
- Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Scores From Baseline to Week 12 of the Double-Blind Period(Baseline, Week 12)
- Mean Change in the Disability Index of the Health Assessment Questionnaire (HAQ) Through Week 92 of the Open-Label Period(Baseline, Week 0, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92)
- Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) and Mental Component Summary (MCS) at Week 12 of the Double-Blind Period(Baseline, Week 12)
- Mean Change in the SF-36 Health Survey Index Physical Component Summary (PCS) Through Week 92 of the Open-Label Period(Baseline, Week 0, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92)
- Mean Change in the SF-36 Health Survey Index Mental Component Summary (MCS) Through Week 92 of the Open-Label Period(Baseline, Week 0, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 92)