Biomarkers in Participants With Hidradenitis Suppurativa Receiving Guselkumab.

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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.

Conditions
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Hidradenitis Suppurativa

Intervention / Treatment
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* Drug: Guselkumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Single Arm Open Label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Guselkumab 200mg q4 weekly | Drug: Guselkumab<br>* Guselkumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers at Week 12 | Change in lesional tissue levels of IL-17A, IL-17C, IL-17F and IL-23, measured in pg/mL | 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 | 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 | Week 0 to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 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) | 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 | 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. | 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) | Week 24 compared with Baseline |