A Study to Evaluate the Efficacy, Safety, and Tolerability of Guselkumab for the Treatment of Participants With Moderate to Severe Hidradenitis Suppurativa (HS)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy, safety, and tolerability of guselkumab in adult participants with moderate to severe hidradenitis suppurativa (HS).

Official Title
-----------------
A Phase 2, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Proof-of-Concept Study to Evaluate Guselkumab for the Treatment of Subjects With Moderate to Severe Hidradenitis Suppurativa

Conditions
-----------------
Hidradenitis Suppurativa

Intervention / Treatment
-----------------
* Drug: Guselkumab dose 1
* Drug: Guselkumab dose 2
* Drug: Guselkumab dose 3
* Drug: Placebo


Participation Criteria
=================
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 the medical history Have HS lesions present in at least 2 distinct anatomic areas (examples include but are not limited to left and right axilla; or left axilla and left inguinocrural fold) Had an inadequate response to an adequate course of appropriate oral antibiotics for treatment of HS (or demonstrated intolerance to, or had a contraindication to oral antibiotics for treatment of their HS) in the investigator's opinion Have a total abscess and inflammatory nodule (AN) count of greater than or equal to (>=) 3 at the screening and baseline visit Must agree to daily use (throughout the entirety of the study) of one of the following over-the-counter treatments to the body areas affected with HS lesions: either soap and water, or a topical antiseptic wash containing chlorhexidine gluconate, triclosan, or benzoyl peroxide, or a dilute bleach bath Exclusion Criteria: Any other active skin disease or condition (example, bacterial, fungal or viral infection) that could have interfered with assessment of HS Has a draining fistula count of greater than (>) 20 at the baseline visit Receipt of prescription topical therapies for the treatment of HS within 14 days prior to the baseline visit Receipt of systemic non-biologic therapies for the treatment of HS less than (<) 4 Weeks prior to the baseline visit Receipt of any oral antibiotic treatment for HS or inflammatory disorders within 4 Weeks prior to the baseline visit

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Guselkumab Regimen 1<br>Participants will receive guselkumab dose 1 administered Intravenously (IV) followed by guselkumab dose 2 administered subcutaneously. | Drug: Guselkumab dose 1<br>* Participants will receive guselkumab dose 1 IV.<br>* Other names: CNTO 1959;Drug: Guselkumab dose 2<br>* Participants will receive guselkumab dose 2 SC in Group 1, 2 and Group 3.<br>* Other names: CNTO 1959;Drug: Placebo<br>* Participants will receive matched placebo SC and IV in group 1, 2 and 3 with an additional placebo SC dose in Group 3.<br>|
| Experimental: Group 2: Guselkumab Regimen 2<br>Participants will receive guselkumab dose 2 subcutaneously. | Drug: Guselkumab dose 2<br>* Participants will receive guselkumab dose 2 SC in Group 1, 2 and Group 3.<br>* Other names: CNTO 1959;Drug: Placebo<br>* Participants will receive matched placebo SC and IV in group 1, 2 and 3 with an additional placebo SC dose in Group 3.<br>|
| Experimental: Group 3: Placebo then Guselkumab<br>Participants will receive placebo IV and SC and an additional SC placebo dose at Week 12 then cross over at Week 16 to receive guselkumab dose 2 and dose 3 SC and placebo SC. | Drug: Guselkumab dose 2<br>* Participants will receive guselkumab dose 2 SC in Group 1, 2 and Group 3.<br>* Other names: CNTO 1959;Drug: Guselkumab dose 3<br>* Participants will receive guselkumab dose 3 SC in Group 3.<br>* Other names: CNTO 1959;Drug: Placebo<br>* Participants will receive matched placebo SC and IV in group 1, 2 and 3 with an additional placebo SC dose in Group 3.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 16 | HiSCR is defined as at least 50 percent (%) reduction in total abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to baseline. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Participant's Total Abscess and Inflammatory Nodule (AN) Count at Week 16 | Change from baseline in total AN count at Week 16 was reported. Abscess and inflammatory nodule were counted for the HS affected anatomical regions. The AN count is the sum of number of abscess and inflammatory nodules across anatomical regions. | Baseline and Week 16 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 16 | DLQI is a simple, compact, and practical questionnaire to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. The participant responds on a four-point scale, ranging from Very Much (score 3) to Not at All or Not relevant (score 0). The DLQI total score is derived by summing all item scores, which has a possible range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best. A lower score (that is, negative change score) indicates improvement in the Quality of Life. | Baseline and Week 16 | 
| Change From Baseline in Hidradenitis Suppurativa (HS)-Related Pain Symptom Score in the Past 24 Hours Based on Hidradenitis Suppurativa Symptom Diary (HSSD) Questionnaire at Week 16 | HSSD is a 7-item patient self-reported questionnaire that assesses 5 HS-related symptoms including pain, tenderness, hot skin feeling, odor, and itchiness. The participants were asked to rate the severity of each symptom on a 0 to 10 numerical rating scale, with 0 indicating no symptom experience and 10 indicating the worst possible symptom experience. All 5 symptoms have a recall period of the past 7 days, except for 2 additional questions on pain which evaluate current pain and pain in the past 24 hours with a score range from 0 (no symptom experience) to 10 (worst possible symptom experience). A total symptom score also ranged from 0 (no symptom) to 10 (worst possible symptom), was derived by averaging the 5 individual scale scores that utilize the past 7-day recall period. Change from baseline in HS-related pain symptom score based on HSSD was reported. | Baseline and Week 16 | 
| Percentage of Participants Who Achieved at Least 50 Percent Reduction in Total Abscess and Inflammatory Nodule Count at Week 16 | Percentage of participants who achieved at least 50 percent reduction in total AN count at Week 16 were reported. Abscess and inflammatory nodule were counted for the HS affected anatomical regions. The AN count is the sum of number of abscess and inflammatory nodules across anatomical regions. | Week 16 | 
| Percentage of Participants Who Achieved at Least 75 Percent Reduction in Total Abscess and Inflammatory Nodule Count at Week 16 | Percentage of participants who achieved at least 75 percent reduction in total AN count at Week 16 were reported. Abscess and inflammatory nodule were counted for the HS affected anatomical regions. The AN count is the sum of number of abscess and inflammatory nodules across anatomical regions. | Week 16 | 
| Percentage of Participants Who Achieved at Least 90 Percent Reduction in Total Abscess and Inflammatory Nodule Count at Week 16 | Percentage of participants who achieved at least 90 percent reduction in total AN count at Week 16 were reported. Abscess and inflammatory nodule were counted for the HS affected anatomical regions. The AN count is the sum of number of abscess and inflammatory nodules across anatomical regions. | Week 16 | 
| Percentage of Participants Who Achieved 100 Percent Reduction in Total Abscess and Inflammatory Nodule Count at Week 16 | Percentage of participants who achieved 100 percent reduction in total AN count at Week 16 were reported. Abscess and inflammatory nodule were counted for the HS affected anatomical regions. The AN count is the sum of number of abscess and inflammatory nodules across anatomical regions. | Week 16 | 
| Percentage of Participants Who Achieved an Abscess and Inflammatory Nodule Count of 0/1 and AN Count of 0/1/2 at Week 16 | Percentage of participants who achieved an AN count of 0/1 and AN Count of 0/1/2 at Week 16 were reported. Abscess and inflammatory nodule were counted for the HS affected anatomical regions. The AN count is the sum of number of abscess and inflammatory nodules across anatomical regions. | Week 16 | 
| Percentage of Participants Who Achieved Abscess Count of 0 at Week 16 For Participants With Baseline Abscess Count Greater Than 0 | Percentage of participants who achieved abscess count of 0 at Week 16 for participants with baseline abscess count greater than (>) 0 were reported. | Week 16 | 
| Change From Baseline in the Number of Abscesses at Week 16 | Change from baseline in number of abscesses at Week 16 was reported. | Baseline and Week 16 | 
| Change From Baseline in HSSD Symptom Scale Total Score at Week 16 | HSSD is a 7-item patient self-reported questionnaire that assesses 5 HS-related symptoms including pain, tenderness, hot skin feeling, odor, and itchiness. The participants were asked to rate the severity of each symptom on a 0 to 10 numerical rating scale, with 0 indicating no symptom experience and 10 indicating the worst possible symptom experience. All 5 symptoms have a recall period of the past 7 days, except for 2 additional questions on pain which evaluate current pain and pain in the past 24 hours. A total symptom score, also ranged from 0 (no symptom) to 10 (worst possible symptom), was derived by averaging the 5 individual scale scores that utilize the past 7-day recall period. | Baseline and Week 16 | 
| Change From Baseline in HSSD Symptom Scale Score (Other Than Pain in the Past 24 Hours) at Week 16 | HSSD is a 7-item patient self-reported questionnaire that assesses 5 HS-related symptoms including pain, tenderness, hot skin feeling, odor, and itchiness. The participants were asked to rate the severity of each symptom on a 0 to 10 numerical rating scale, with 0 indicating no symptom experience and 10 indicating the worst possible symptom experience. All 5 symptoms have a recall period of the past 7 days, except for 2 additional questions on pain which evaluate current pain and pain in the past 24 hours. Change from baseline in each individual HSSD component scale (other than pain in the past 24 hours) tenderness, hot skin feeling, odor and itchiness symptom, pain, and current pain score (rated on a scale of 0 [no symptom experience] to 10 [worst possible symptom experience]) were reported. | Baseline and Week 16 | 
| Percentage of Participants Who Achieved Draining Fistula Count of 0 at Week 16 for Participants With Baseline Draining Fistula Count Greater Than 0 | Percentage of participants who achieved draining fistulas count of 0 at Week 16 for participants with baseline draining fistula count >0 were reported. Draining fistula were defined as fistulas that drain serous or purulent fluid, either spontaneously or by gentle palpation. | Week 16 | 
| Change From Baseline in Number of Draining Fistulas at Week 16 | Change from baseline in number of draining fistulas at Week 16 was reported. Draining fistula are defined as fistulas that drain serous or purulent fluid, either spontaneously or by gentle palpation. | Baseline and Week 16 | 
| Percentage of Participants Who Achieved Inflammatory Nodules Count of 0 at Week 16 for Participants With Baseline Inflammatory Nodule Count Greater Than 0 | Percentage of participants who achieved inflammatory nodules count of 0 at Week 16 in participants with baseline inflammatory nodules count >0 were reported. | Week 16 | 
| Change From Baseline in Number of Inflammatory Nodules at Week 16 | Change from baseline in number of inflammatory nodules at Week 16 was reported. | Baseline and Week 16 | 
| Percentage of Participants With Hidradenitis Suppurativa-investigator's Global Assessment (HS-IGA) Score of Inactive (0), Almost Inactive (1), or Mild Activity (2) and With at Least 2-Grade Improvement Relative to Baseline at Week 16 | The HS-IGA documents the investigator's assessment of the participant's HS at a given timepoint. The anatomic region with the most severe HS activity at the baseline was evaluated for erythema, drainage, and pain and/or tenderness to palpation for each participant. The participant's HS is assessed as inactive (0), almost inactive (1), mild activity (2), moderate activity (3), or severe activity (4). A higher score indicates more severe disease. Percentage of participants with HS-IGA score of inactive (0), almost inactive (1), or mild activity (2) and with at least 2-grade improvement relative to baseline at Week 16 were reported. | Week 16 | 
| Percentage of Participants With HS-IGA Score of Inactive (0) or Almost Inactive (1) at Week 16 Among Participants With HS-IGA Score of Moderate Activity (3) or Severe Activity (4) at Baseline | The HS-IGA documents the investigator's assessment of the participant's HS at a given timepoint. The anatomic region with the most severe HS activity at the baseline was evaluated for erythema, drainage, and pain and/or tenderness to palpation for each participant. Among participants with score of moderate activity (3) or severe activity (4) at baseline, the same anatomic site selected for evaluation at the baseline were re-evaluated at Week 16. The participant's HS is assessed as inactive (0), almost inactive (1), mild activity (2), moderate activity (3), or severe activity (4). A higher score indicates more severe disease. Percentage of participants with HS-IGA score of inactive (0), almost inactive (1) at Week 16 among participants with HS-IGA score of moderate activity (3) or severe activity (4) at baseline were reported. | Week 16 | 
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 16 | The HADS has been developed to identify symptoms of anxiety and depression in hospitalized participants and in outpatients. It comprises 14 items, seven to assess anxiety (HADS-A), namely items 1, 3, 5, 7, 9, 11, and 13; and seven to assess depression (HADS-D), namely items 2, 4, 6, 8, 10, 12, and 14. Each item receives a score from 0 to 3 on a Likert Scale. The total score for each HADS-A and HADS-D scale is obtained by adding the individual scores for each item, with the maximum score 21. The presence or absence of depression and anxiety was defined, for each respective scale, based on the following cutoff values: HADS (anxiety): 0-8 equal to (=) no anxiety; greater than (>) 9 = anxiety; HADS (depression): 0-8 = no depression; >9 = depression. | Baseline and Week 16 | 
| Change From Baseline in High-sensitivity C-Reactive Protein (Hs-CRP) at Week 16 | Change from baseline in hs-CRP at Week 16 was reported. Serum samples were collected and analyzed for hsCRP. Change from Baseline was calculated as: ([hs-CRP value at Week 16 minus Baseline value] divided by [Baseline value]). | Baseline and Week 16 | 
| Number of Participants With Patient Global Impression of Change (PGIC) of Hidradenitis Suppurativa Severity Scale Score at Week 16 | The PGIC of HS Severity is a questionnaire that measures participants' perceived change (improvement or deterioration) in severity of their HS. Participants rated how his/her HS has changed since the beginning of the study using a 7-point scale ranging from 1 which indicates a lot better now to 7 which indicates a lot worse now with a neutral center point 4 which indicates (neither better nor worse). Participants' PGIC of HS Severity scale score at Week 16 were reported | Week 16 |