Biomarkers in Participants With Hidradenitis Suppurativa Receiving Guselkumab.

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.

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.

Study Overview

• Status: Withdrawn
• Conditions: Hidradenitis Suppurativa
• Intervention / Treatment: Drug: Guselkumab

Detailed Description

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
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Rockefeller Unviersity

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Guselkumab 200mg q4 weekly	Drug: Guselkumab; Guselkumab

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rockefeller University
• Collaborators: Janssen Scientific Affairs, LLC

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): July 30, 2020
• Study Completion (Anticipated): July 30, 2020

Study Registration Dates

• First Submitted: September 9, 2019
• First Submitted That Met QC Criteria: September 9, 2019
• First Posted (Actual): September 10, 2019

Study Record Updates

• Last Update Posted (Actual): June 5, 2020
• Last Update Submitted That Met QC Criteria: June 3, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Sweat Gland Diseases; Skin Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Suppuration; Skin Diseases, Bacterial; Hidradenitis Suppurativa; Hidradenitis
• Other Study ID Numbers: JFR-0992

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No