A Pilot Study to Examine Safety, Activity and Biomarkers in Participants With Hidradenitis Suppurativa Receiving a Previously Tested Subcutaneous Dose of Anti-IL-23 Monoclonal Antibody Guselkumab.
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Biomarkers at Week 12
研究概览
简要总结
Hidradenitis Suppurativa (HS) is a severe, chronic debilitating disease with a variable and incomplete response to current treatments. Existing immunological studies have found dysregulation in the TH17:Treg axis with an increase in inflammatory mediators including TNFalpha, IL-17 IL-23 (amongst others) in lesional skin. Multiple cell typesincluding CD4+ cells, dendritic cells and macrophages infiltrate active lesions of HS and produce this major contribution from the Th17 axis.
One of the main barriers to the development of novel and effective treatments for HS is the lack of biomarker(s) of disease activity, as well as our incomplete understanding of the pathogenesis of this disease. Given the pronounced contribution of Th17 pathway (including interleukin-23) in the inflammation in HS, further investigation into the role of this axis in the pathogenicity of HS is essential. Guselkumab is a fully human interluekin-23 antagonist, FDA approved for the treatment of moderate to severe psoriasis in participants 18 years and over. Guselkumab is a novel potential therapy.
详细描述
Hidradenitis Suppurativa (HS) is a severe, chronic debilitating disease with a variable and incomplete response to current treatments. Existing immunological studies have found dysregulation in the TH17:Treg axis with an increase in inflammatory mediators including TNFalpha, IL-17 IL-23 (amongst others) in lesional skin. Multiple cell typesincluding CD4+ cells, dendritic cells and macrophages infiltrate active lesions of HS and produce this major contribution from the Th17 axis.
One of the main barriers to the development of novel and effective treatments for HS is the lack of biomarker(s) of disease activity, as well as our incomplete understanding of the pathogenesis of this disease. Markers such as C- Reactive Protein, IL-6, soluble IL-2 receptor, S100A8/9, lipocalin-2 and the neutrophil/lymphocyte rati7 have been proposed as potential biomarkers but lack high specificity and correlation with disease severity. Given the pronounced contribution of Th17 pathway (including interleukin-23) in the inflammation in HS, further investigation into the role of this axis in the pathogenicity of HS is essential. Guselkumab is a fully human interluekin-23 antagonist, FDA approved for the treatment of moderate to severe psoriasis in participants 18 years and over. Guselkumab is a novel potential therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
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
- •Have moderate to severe Hidradenitis Suppurativa (HS) for at least 1 year (365 days) prior to the baseline visit as determined by the investigator through participant interview and/or review of medical history
- •Have HS lesions present in at least 2 distinct anatomical areas
- •Had an inadequate response to an adequate course of appropriate oral antibiotics for treatment of HS (or demonstrated intolerance to, or had contraindications to oral antibiotic treatment of their HS
- •Have a total abscess and inflammatory nodule (AN) count greater than or equal to 3 at the screening and baseline visit
- •Must agree with daily use (throughout the study of one of the following over the counter treatments to body areas affected with HS lesions: either soap and water, a topical antiseptic was containing chlorhexidine gluconate, triclosan or benzoyl peroxide, or a dilute bleach bath.
排除标准
- •HIV Positive
- •Active Hepatitis B or C Infection
- •Pregnant or Breastfeeding
- •No concurrent use of any systemic antibiotics/retinoids/immunosuppressants (require washout period of 5 half lives)
- •Any medical, psychological or social condition that, in the opinion of the investigator would jeopardize the health or well being of the participant during any study procedures or integrity of the data
- •Has a draining fistula count greater than 20 at baseline visit Any other active skin disease (bacterial fungal or viral infection) that could have interfered with the assessment of HS
研究组 & 干预措施
Intervention
Guselkumab 200mg q4 weekly
干预措施: Guselkumab (Drug)
结局指标
主要结局
Biomarkers at Week 12
时间窗: Week 12 compared with baseline (Week 0).
Change in lesional tissue levels of IL-17A, IL-17C, IL-17F and IL-23, measured in pg/mL
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
时间窗: Week 0 to Week 24
Incidence of Grade 2/3 adverse events during the study
Biomarkers at Week 24
时间窗: Week 24 compared with baseline (Week 0).
Primary Outcomes would be the change in lesional tissue levels of IL-17A, IL-17C, IL-17F and IL-23 measured in pg/mL measured in pg/mL
次要结局
- Clinical Response at Week 12 (as measured by HiSCR)(Week 12 compared with Baseline)
- Clinical Response at Week 12 (as measured by IHS4)(Week 12 compared with Baseline)
- Clinical Response at Week 24 (as measured by HiSCR)(Week 24 compared with Baseline)
- Clinical Response at Week 24 (as measured by modified Sartorius Score)(Week 24 compared with Baseline)
- Clinical Response at Week 24 (as measured by IHS4)(Week 24 compared with Baseline)
- Clinical Response at Week 12 (as measured by modified Sartorius Score)(Week 12 compared with Baseline)