An Exploratory, Randomized, Double-blind, Parallel-group, Multicenter Study to Compare Secukinumab 300 mg With Placebo After 16 Weeks of Treatment in Adults With Moderate to Severe Plaque Psoriasis and Subclinical Enthesitis Measured by Musculoskeletal Ultrasound
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 主要终点
- Change from Baseline in the Outcome Measures in Rheumatology (OMERACT) ultrasound enthesitis score
研究概览
简要总结
Given the role of IL-17 in the development of entheseal-driven pathology, a therapeutic strategy aimed at blocking IL-17 would be a logical option for the treatment of subclinical enthesitis in psoriasis patients. This study will be the first randomized trial of a biologic therapy versus placebo in participants with plaque psoriasis and subclinical psoriatic arthritis, using musculoskeletal ultrasound.
详细描述
The primary objective of this study is to estimate the difference in effect between secukinumab 300 mg s.c. and placebo, based on change from baseline to Week 16 in the OMERACT ultrasound enthesitis score.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of chronic plaque-type psoriasis confirmed through physical examination by a dermatologist, with at least six months of clinical history prior to the baseline visit
- •Moderate to severe plaque psoriasis at baseline as defined as:
- •≥ 10 % Body Surface Area (BSA) involvement, or
- •≥ 3% to <10% Body Surface Area with involvement of special regions (nails, scalp, or intertriginous skin), or with a history of psoriatic arthritis in a parent
- •Candidate for systemic therapy, defined as having psoriasis inadequately controlled by current topical and/or systemic treatment(s) (including topical corticosteroids), phototherapy, or previous systemic therapies
- •Presence of sonographic enthesitis at screening, in at least one enthesis, defined by the presence of at least abnormal thickening and hypoechogenicity of the tendon insertion, with or without presence of Doppler signal (Grade 0-3), or by the presence of grade ≥ 2 Doppler signal, independent of gray scale abnormalities
排除标准
- •Diagnosis of PsA as per CASPAR confirmed by a rheumatologist (including the presence of inflammatory pain in entheses or joints), and any other known rheumatological disease affecting the assessed joints
- •Exposure to any IL-17 or IL-23(p19) inhibitor for the treatment of psoriasis (approved or investigational) within twelve months prior to screening, or exposure to any inhibitors of TNF-ɑ and IL12/23 within six months prior to screening
- •Previous exposure to non-biologic systemic therapy for psoriasis, including methotrexate, PDE-4 inhibitors, or systemic corticosteroids within 12 weeks or 5 half-lives (whichever is longer) prior to screening
- •A degree of obesity that impedes proper ultrasound examination of entheses and joints
- •Forms of diagnosed psoriasis other than chronic plaque psoriasis (e.g., erythrodermic, generalized or localized pustular psoriasis, or new onset guttate psoriasis)
- •Other protocol-defined inclusion/exclusion criteria may apply
结局指标
主要结局
Change from Baseline in the Outcome Measures in Rheumatology (OMERACT) ultrasound enthesitis score
时间窗: Baseline and Week 16
Twelve (12) entheses (bilateral AT, LE, PP, DP, PA, QT) will be scored in terms of inflammatory and morphological components according to the OMERACT enthesitis composite semi-quantitative scale (0 to 3). The lowest OMERACT score a participant can have at baseline is 2 (based on Inclusion Criterion number 6, which requires at least 2 points in the B-mode or the Doppler mode in at least one enthesis). The highest OMERACT score expected at baseline will be 72, assuming that each of the 12 entheses assessed shows a maximum of 3 points in the gray scale score, and a maximum of 3 points in the Doppler score. The largest change expected from baseline to Week 16 is -60 points (improvement). This assumes that the presence of structural changes (calcifications, enthesophytes and erosions) may add a maximum of 12 points to the score, and it may not be modifiable with study treatment during the study period.
次要结局
- Change from Baseline in Body Surface Area (BSA)(Baseline and Week 16)
- Change from Baseline in Dermatology Life Quality Index (DLQI) score(Baseline and Week 16)
- Number of participants who achieve complete resolution of enthesitis based on OMERACT criteria (yes, no)(Baseline and Week 16)
- Change from Baseline in HAQ-DI score(Baseline and Week 16)
- Change from Baseline in the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) ultrasound enthesitis score(Baseline and Week 16)
- Number of participants who achieve Psoriasis Area and Severity Index 100 (PASI 100) (yes, no)(Baseline and Week 16)
- Number of participants who achieve Investigator's Global Assessment modified 2011 (IGA mod 2011) score of 0 or 1 (yes, no)(Baseline and Week 16)
- Change from Baseline in the PsASon13 unilateral ultrasound composite score of synovitis(Baseline and Week 16)
- Number of participants who achieve Psoriasis Area and Severity Index 90 (PASI 90) (yes, no)(Baseline and Week 16)
- Number of participants who achieve HAQ-DI change from baseline ≤ -0.35 (yes, no)(Baseline and Week 16)
- Number of participants who achieve Dermatology Life Quality Index (DLQI) score of 0 or 1 (yes, no)(Baseline and Week 16)