Mechanism of Action Study of Anti-IL17 Treatment in Spondyloarthritis: Impact on Cellular and Molecular Pathways of Synovial Inflammation and Tissue Remodeling
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Changes of cellular infiltrate in the target tissue (synovium)
研究概览
简要总结
The purpose of this study is to determine the mechanism of action on target tissue level of anti Interleukine-17 (anti-IL-17) an therapy in peripheral spondyloarthritis.
Patients will be treated with anti-IL-17 therapy (secukinumab) for 12 weeks and with a 2 year extension period thereafter.
At week 0 and 12 peripheral blood, synovial tissue and skin will be analysed with different techniques, including immunohistochemistry, RNA analysis and tissue culture to assess the effect of the therapy on inflammatory pathways.
详细描述
Background of the study:
Spondyloarthritis is the second most frequent form of chronic inflammatory arthritis with a prevalence of 0.5%. It effects mainly young adults and leads to major functional handicap due to inflammation of axial and peripheral joints as well as progressive ankylosis and structural damage.
In the late nineties Tumor Necrosis Factor (TNF) blockade was introduced as a successful treatment, but: only 50% responds well and tolerates, a-TNF does not halt the structural damage and TNF blockade does not induce long lasting remission as almost all patients relapse within a few weeks after interruption of the treatment. There is thus a high unmet need for alternatives.
The rationale for anti-IL17 therapy is based on various auto-inflammatory and auto immune models, preliminary efficacy data in psoriasis and Rheumatoid arthritis (RA) and an association of SpA with Interleukin 23 Receptor (IL23R) single nucleotide polymorphism (SNP).
Efficacy data on anti-IL17 shows that it is a highly effective treatment for signs and symptoms in SpA, moreover sub-analysis of the anti-TNF naïve patients shows the same trend.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or non-pregnant/non-lactating females age 18-70
- •Diagnosis of SpA according to ESSG criteria and/or ASAS criteria
- •Active disease defined by ≥1 swollen and ≥ 1 tender joint, and at least 1 swollen knee or ankle joint at baseline
排除标准
- •Evidence for infectious or malignant process (on chest X ray/MRI etc)
- •Patients taking opioid analgetics
- •Previous IL-17 therapy exposure
- •Previous use of cell-depleting therapies, biological immunomodulators (except for TNF blockade , as 25% may have been previously treated with 1 TNF blocking agent)
- •Significant medical problems or diseases
研究组 & 干预措施
Secukinumab
All patients will be treated with active treatment. (anti-IL17)
干预措施: Secukinumab (Drug)
结局指标
主要结局
Changes of cellular infiltrate in the target tissue (synovium)
时间窗: week 0 and week 12
Changes in cell count measured by immunohistochemistry (on a 0-4 semi-quantitative analysis scale)
Biological changes induced by therapy on target tissue (synovium)
时间窗: week 0 and week 12
Molecular changes of the synovium as measured by expression of several cytokines/chemokines by quantitative polymerase chain reaction (qPCR) as measured by a change in cytokine expression between baseline and week 12.
次要结局
- Adverse events(between day0 and 2 yrs of treatment)
- Vessel wall inflammation(week 0 and week 12)
研究者
D.L.P. Baeten
Professor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)