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Biomarkers in Participants With Hidradenitis Suppurativa Receiving Guselkumab.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04084665
Recruitment Status : Withdrawn (COVID-19 Pandemic)
First Posted : September 10, 2019
Last Update Posted : June 5, 2020
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Rockefeller University

Tracking Information
First Submitted Date  ICMJE September 9, 2019
First Posted Date  ICMJE September 10, 2019
Last Update Posted Date June 5, 2020
Estimated Study Start Date  ICMJE June 1, 2020
Estimated Primary Completion Date July 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 9, 2019)
  • Biomarkers at Week 12 [ Time Frame: 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
  • Biomarkers at Week 24 [ Time Frame: 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
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Week 0 to Week 24 ]
    Incidence of Grade 2/3 adverse events during the study
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2019)
  • Clinical Response at Week 12 (as measured by HiSCR) [ Time Frame: Week 12 compared with Baseline ]
    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
  • Clinical Response at Week 12 (as measured by modified Sartorius Score) [ Time Frame: Week 12 compared with Baseline ]
    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.
  • Clinical Response at Week 12 (as measured by IHS4) [ Time Frame: Week 12 compared with Baseline ]
    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)
  • Clinical Response at Week 24 (as measured by HiSCR) [ Time Frame: Week 24 compared with Baseline ]
    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
  • Clinical Response at Week 24 (as measured by modified Sartorius Score) [ Time Frame: Week 24 compared with Baseline ]
    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.
  • Clinical Response at Week 24 (as measured by IHS4) [ Time Frame: Week 24 compared with Baseline ]
    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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Biomarkers in Participants With Hidradenitis Suppurativa Receiving Guselkumab.
Official Title  ICMJE 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Single Arm Open Label
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Hidradenitis Suppurativa
Intervention  ICMJE Drug: Guselkumab
Guselkumab
Study Arms  ICMJE Experimental: Intervention
Guselkumab 200mg q4 weekly
Intervention: Drug: Guselkumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: June 3, 2020)
0
Original Estimated Enrollment  ICMJE
 (submitted: September 9, 2019)
10
Estimated Study Completion Date  ICMJE July 30, 2020
Estimated Primary Completion Date July 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04084665
Other Study ID Numbers  ICMJE JFR-0992
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Rockefeller University
Study Sponsor  ICMJE Rockefeller University
Collaborators  ICMJE Janssen Scientific Affairs, LLC
Investigators  ICMJE
Principal Investigator: John W Frew, MD Rockefeller University
PRS Account Rockefeller University
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP