Clinical trial NCT04084665: Biomarkers in Participants With Hidradenitis Suppurativa Receiving Guselkumab.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Hidradenitis Suppurativa
Lead sponsor: Rockefeller University
Sponsor class: OTHER
Collaborators: name: Janssen Scientific Affairs, LLC
First posted: 2019-09-10
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Arm Open Label
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Biomarkers at Week 12
timeFrame: Week 12 compared with baseline (Week 0).
measure: Biomarkers at Week 24
timeFrame: Week 24 compared with baseline (Week 0).
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Week 0 to Week 24
Secondary outcomes:
measure: Clinical Response at Week 12 (as measured by HiSCR)
timeFrame: Week 12 compared with Baseline
measure: Clinical Response at Week 12 (as measured by modified Sartorius Score)
timeFrame: Week 12 compared with Baseline
measure: Clinical Response at Week 12 (as measured by IHS4)
timeFrame: Week 12 compared with Baseline
measure: Clinical Response at Week 24 (as measured by HiSCR)
timeFrame: Week 24 compared with Baseline
measure: Clinical Response at Week 24 (as measured by modified Sartorius Score)
timeFrame: Week 24 compared with Baseline
measure: Clinical Response at Week 24 (as measured by IHS4)
timeFrame: Week 24 compared with Baseline
Other outcomes:
Locations:
city: New York
country: United States
facility: Rockefeller Unviersity
state: New York
Study officials:
affiliation: Rockefeller University
name: John W Frew, MD
role: PRINCIPAL_INVESTIGATOR
References: