A Multicenter, Randomized, Double-Blind, Study Comparing the Efficacy and Safety of Continuing Versus Withdrawing Adalimumab Therapy in Maintaining Remission in Subjects With Non-Radiographic Axial Spondyloarthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 673
- 主要终点
- Number of Participants Who Did Not Experience a Flare During Period 2 by Week 68
研究概览
简要总结
The objective of this multicenter, randomized, double-blind study was to evaluate the efficacy and safety of continuing versus withdrawing therapy with adalimumab 40 mg given every other week SC in maintaining remission in subjects with moderate to severe non-radiographic axial spondyloarthritis.
详细描述
The study duration included a 42-day Screening Period, a 28-week open-label 40 mg adalimumab every other week (eow) treatment period (Period 1), a 40-week double-blind placebo controlled eow treatment period (Period 2) with an opportunity to receive at least 12 weeks of rescue therapy with open-label adalimumab (participants that flared at Weeks 60, 64 or 68 were allowed 12 weeks of rescue therapy and final visits were at Weeks 72, 76 or 80 respectively), plus a 70-day follow-up phone call. Participants in sustained Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease were randomized at Week 28 at a 1:1 ratio to receive either blinded adalimumab 40 mg eow or matching placebo. The length of exposure to adalimumab depended on remission or flare status and ranged from 20 (first time Ankylosing Spondylitis Disease Activity Score [ASDAS] remission was calculated) to 80 weeks of treatment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult participants with inadequate response to ≥2 nonsteroidal anti-inflammatory drugs (NSAIDs)
- •Participants with non-radiographic axial spondyloarthritis fulfilling the Assessment of Spondyloarthritis International Society (ASAS) axial SpA classification criteria, but not fulfilling the radiologic criterion of the modified New York criteria for ankylosing spondylitis
- •Participants must have baseline disease activity as defined by having an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥ 2.100, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 and Patient's Assessment of Total Back Pain score ≥ 4 based on a Numeric Rating Scale (NRS) at both the screening and baseline visits
- •Participants with evidence of active inflammation in the sacroiliac (SI) joints or spine on MRI, or elevated high sensitivity C-reactive protein (hs-CRP) at screening
- •Negative tuberculosis (TB) screening assessment
- •Ability to administer subcutaneous injections or have a qualified person available to administer injections
- •If female, either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy) or of childbearing potential and practicing an approved method of birth control throughout the study and for 150 days after last dose of study drug.
- •Participant 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, and a 12-lead electrocardiogram performed at screening
排除标准
- •Prior anti-Tumor Necrosis Factor (TNF) therapy; biologic therapy with a potential therapeutic impact on SpA or treated with an investigational drug of chemical or biologic nature within 30 days or 5 half-lives prior to the baseline visit.
- •Fulfillment of the radiologic criterion of the modified New York criteria for Ankylosing Spondylitis at or prior to the screening visit
- •Recent infection 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
- •Significant medical events or conditions that may put participants at risk for participation
- •Female participants who are pregnant or breast-feeding or considering becoming pregnant during the study
- •Known hypersensitivity to adalimumab or its excipients as stated in the label
研究组 & 干预措施
Double-Blind Adalimumab
40 mg every other week (eow), Weeks 28-68. Blinded adalimumab was discontinued in participants who met the criteria for flare.
干预措施: adalimumab (Biological)
Open-label (OL) Adalimumab
40 mg every other week (eow), Weeks 0-28. If participants flared during the double-blind period, they had an opportunity to receive at least 12 weeks of open-label adalimumab 40 mg eow.
干预措施: adalimumab (Biological)
Placebo
Placebo every other week (eow), Weeks 28-68. Placebo was discontinued in participants who met the criteria for flare.
干预措施: Placebo (Biological)
结局指标
主要结局
Number of Participants Who Did Not Experience a Flare During Period 2 by Week 68
时间窗: From Week 28 through 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A flare was defined as having any 2 consecutive study visits with ASDAS ≥ 2.100.
次要结局
- Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at 12 Weeks After Initiation of Rescue Therapy(Rescue Therapy Week 12)
- Number of Participants Achieving ASAS Partial Remission at 12 Weeks After Initiation of Rescue Therapy(Rescue Therapy Week 12)
- Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at 12 Weeks After Initiation of Rescue Therapy(Baseline and Rescue Therapy Week 12)
- Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at 12 Weeks After Initiation of Rescue Therapy(Baseline and Rescue Therapy Week 12)
- Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at Weeks 28 and 68(Baseline, Weeks 28 and 68)
- Time to Flare at Week 68(From Week 28 through 68)
- Number of Participants Achieving ASDAS Major Improvement at 12 Weeks After Initiation of Rescue Therapy(Baseline and Rescue Therapy Week 12)
- Number of Participants Achieving ASDAS Clinically Important Improvement at 12 Weeks After Initiation of Rescue Therapy(Baseline and Rescue Therapy Week 12)
- Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at 12 Weeks After Initiation of Rescue Therapy(Baseline and Rescue Therapy Week 12)
- Number of Participants Achieving an ASAS 5/6 Response at 12 Weeks After Initiation of Rescue Therapy(Baseline and Rescue Therapy Week 12)
- Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at 12 Weeks After Initiation of Rescue Therapy(Baseline and Rescue Therapy Week 12)
- Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at Weeks 28 and 68(Weeks 28 and 68)
- Number of Participants Achieving an ASAS 5/6 Response at Weeks 28 and 68(Baseline, Weeks 28 and 68)
- Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at Weeks 28 and 68(Baseline, Weeks 28 and 68)
- Time to Partial Flare at Week 68(From Week 28 through 68)
- Number of Participants Achieving ASDAS Major Improvement at Weeks 28 and 68(Baseline, Weeks 28 and 68)
- Number of Participants Achieving ASDAS Clinically Important Improvement at Weeks 28 and 68(Baseline, Weeks 28 and 68)
- Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at Weeks 28 and 68(Baseline, Weeks 28 and 68)
- Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Weeks 28 and 68(Baseline, Weeks 28 and 68)
- Number of Participants Achieving ASAS Partial Remission at Weeks 28 and 68(Baseline, Weeks 28 and 68)
- Number of Participants Reaching Partial Flare Definition by Week 68(From Week 28 through 68)
- Number of Participants Reaching Flare Definition by Week 68(From Week 28 through 68)