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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Guselkumab
Rockefeller Unviersity
New York, New York, United States
Biomarkers at Week 12
Change in lesional tissue levels of IL-17A, IL-17C, IL-17F and IL-23, measured in pg/mL
Time frame: Week 12 compared with baseline (Week 0).
Biomarkers at Week 24
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
Time frame: Week 24 compared with baseline (Week 0).
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Incidence of Grade 2/3 adverse events during the study
Time frame: Week 0 to Week 24
Clinical Response at Week 12 (as measured by HiSCR)
Clinical Response compared to baseline as assessed by the HiSCR (Hidradenitis Suppurativa Clinical Response) Defined as a greater than or equal to 50% reduction in inflammatory lesion count (abscesses plus inflammatory nodules), and no increase in abscesses or draining fistulas at Week 12 when compared with baseline
Time frame: Week 12 compared with Baseline
Clinical Response at Week 12 (as measured by modified Sartorius Score)
Clinical Response compared to baseline as assessed by the modified Sartorius Score as follows: Sum of separate scoring for each affected area using the data recorded as follows: a) 3 points per anatomical region involved; b) 6 points for each fistula and 1 point for each nodule or abscess; c) 1 point when the longest distance between two relevant lesions in each affected area is \<5 cm; 3 points when it is 5-10 cm; and 9 points when it is \>10 cm; d) 9 points when there is no clear separation of lesions from adjacent normal skin and 0 points when there is.
Time frame: Week 12 compared with Baseline
Clinical Response at Week 12 (as measured by IHS4)
Clinical Response compared to baseline as assessed by IHS4 (International Hidradenitis Suppurativa Severity Score) using the scoring system as follows: Total= (Number of nodules x1) + (Number of abscesses x2) + (Number of draining sinuses/fistulae x4)
Time frame: Week 12 compared with Baseline
Clinical Response at Week 24 (as measured by HiSCR)
Clinical Response compared to baseline as assessed by the HiSCR (Hidradenitis Suppurativa Clinical Response) Defined as a greater than or equal to 50% reduction in inflammatory lesion count (abscesses plus inflammatory nodules), and no increase in abscesses or draining fistulas at Week 24 when compared with baseline
Time frame: Week 24 compared with Baseline
Clinical Response at Week 24 (as measured by modified Sartorius Score)
Clinical Response compared to baseline as assessed by the modified Sartorius Score as follows: Sum of separate scoring for each affected area using the data recorded as follows: a) 3 points per anatomical region involved; b) 6 points for each fistula and 1 point for each nodule or abscess; c) 1 point when the longest distance between two relevant lesions in each affected area is \<5 cm; 3 points when it is 5-10 cm; and 9 points when it is \>10 cm; d) 9 points when there is no clear separation of lesions from adjacent normal skin and 0 points when there is.
Time frame: Week 24 compared with Baseline
Clinical Response at Week 24 (as measured by IHS4)
Clinical Response compared to baseline as assessed by IHS4 (International Hidradenitis Suppurativa Severity Score) using the scoring system as follows: Total= (Number of nodules x1) + (Number of abscesses x2) + (Number of draining sinuses/fistulae x4)
Time frame: Week 24 compared with Baseline
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