A Study of Bermekimab for the Treatment of Participants With Moderate to Severe Hidradenitis Suppurativa

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the clinical efficacy of bermekimab in participants with moderate to severe Hidradenitis Suppurativa (HS).

Detailed Description
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Hidradenitis suppurativa (HS) is a chronic skin disease of unclear etiology that affects 1 percent (%) to 4% of the general population. JNJ-77474462 (bermekimab) is a recombinant human immunoglobulin G1 kappa (IgG1k) monoclonal antibody (mAb) that binds with high affinity and selectivity for human interleukin-1 alpha (IL-1 alpha) and is an effective blocker of IL-1 alpha biological activity. IL-1 alpha is a key mediator of sterile inflammatory responses. Skin is a significant reservoir of preformed IL-1 alpha, and it has been postulated that IL-1 alpha may play a role in the pathophysiology of multiple inflammatory skin disorders, including HS. Part 1 of this study contains 4 study periods: up to 6 weeks screening period (Period 1), 16-week placebo-controlled period (Period 2), 16-week cross over period (Period 3), and 4-week safety follow-up (Period 4). Part 2 of this study also contains 4 study periods: up to 6 weeks screening period (Period 1), 12-week placebo-controlled period (Period 2), 20-week cross over period (Period 3), and 4-week safety follow up (Period 4). Safety will be assessed by adverse events (AEs), serious adverse event (SAEs), physical examinations, vital signs, electrocardiograms, clinical safety laboratory assessments, allergic reaction, injection-site reactions, and tuberculosis evaluations. The total duration of study participation will be up to 42 weeks.

Official Title
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A Phase 2a/2b, Multicenter, Randomized, Placebo and Active Comparator-controlled, Double-Blind, Dose-ranging Study to Evaluate the Safety and Efficacy of Bermekimab (JNJ-77474462) for the Treatment of Subjects With Moderate to Severe Hidradenitis Suppurativa

Conditions
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Hidradenitis Suppurativa

Intervention / Treatment
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* Drug: Bermekimab
* Drug: Adalimumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have 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 Hurley Stage II or Hurley Stage III HS as determined by the investigator at screening and baseline visits 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) at screening and baseline visits Have a total abscess and inflammatory nodule (AN) count of greater than or equal to (>=) 5 at the screening and baseline visit Agree not to receive a live virus or live bacterial vaccination during the study and for 90 days after the last administration of study intervention Exclusion Criteria: Has a current diagnosis or signs or symptoms of severe, progressive, or uncontrolled renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances Has unstable cardiovascular disease, defined as a recent clinical deterioration (that is, unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiac hospitalization within the last 3 months Has or has had herpes zoster within the 2 months before screening Has a transplanted organ (with exception of a corneal transplant greater than [>] 3 months before the first administration of study intervention) Has known allergies, hypersensitivity, or intolerance to bermekimab or adalimumab or its excipients

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Part 1 (Group 1): Placebo<br>Participants will receive placebo subcutaneously (SC) at Week 0 through Week 15. At Week 16, participants will cross over to receive bermekimab dose 1 SC every week thereafter through Week 31. | Drug: Bermekimab<br>* Bermekimab will be administered subcutaneously.<br>* Other names: JNJ-77474462;Drug: Placebo<br>* Placebo will be administered subcutaneously.<br>|
| Active Comparator: Part 1 (Group 2): Adalimumab<br>Participants will receive adalimumab 160 milligrams (mg) SC at Week 0, placebo SC at Week 1, followed by adalimumab 80 mg SC and placebo SC at Weeks 2 and 3. Participants will then receive adalimumab 40 mg SC and placebo SC at Week 4 and every week thereafter through Week 31. | Drug: Adalimumab<br>* Adalimumab will be administered subcutaneously.<br>Drug: Placebo<br>* Placebo will be administered subcutaneously.<br>|
| Experimental: Part 1 (Group 3): Bermekimab Dose 1<br>Participants will receive bermekimab dose 1 SC and placebo SC at Week 0, followed by bermekimab dose 1 SC at Week 1 and every week thereafter through Week 31. | Drug: Bermekimab<br>* Bermekimab will be administered subcutaneously.<br>* Other names: JNJ-77474462;Drug: Placebo<br>* Placebo will be administered subcutaneously.<br>|
| Placebo Comparator: Part 2 (Group 1): Placebo<br>Participants will receive placebo SC from Week 0 through Week 11. At Week 12, participants will cross over to receive bermekimab dose 1 SC weekly through Week 31. | Drug: Bermekimab<br>* Bermekimab will be administered subcutaneously.<br>* Other names: JNJ-77474462;Drug: Placebo<br>* Placebo will be administered subcutaneously.<br>|
| Experimental: Part 2 (Group 2): Bermekimab Dose 1<br>Participants will receive bermekimab dose 1 SC at Week 0 and every week thereafter through Week 31. | Drug: Bermekimab<br>* Bermekimab will be administered subcutaneously.<br>* Other names: JNJ-77474462;|
| Experimental: Part 2 (Group 3): Bermekimab Dose 1<br>Participants will receive bermekimab dose 1 SC at Week 0 and every week thereafter through Week 11. From Week 12, participants will receive bermekimab dose 1 SC every other week thereafter through Week 30. During weeks in which bermekimab is not administered, participants will receive placebo SC through Week 31. | Drug: Bermekimab<br>* Bermekimab will be administered subcutaneously.<br>* Other names: JNJ-77474462;Drug: Placebo<br>* Placebo will be administered subcutaneously.<br>|
| Experimental: Part 2 (Group 4): Bermekimab Dose 2<br>Participants will receive bermekimab dose 2 SC and placebo SC at Week 0 and every week thereafter through Week 11. From Week 12, participants will receive bermekimab dose 2 SC and placebo SC every other week thereafter through Week 30. During weeks in which bermekimab is not administered, participants will receive placebo SC through Week 31. | Drug: Bermekimab<br>* Bermekimab will be administered subcutaneously.<br>* Other names: JNJ-77474462;Drug: Placebo<br>* Placebo will be administered subcutaneously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Percentage of Participants Who Achieved Hidradenitis Suppurativa Clinical Response-50 (HiSCR50) at Week 16 | HiSCR50 was defined as at least 50 percent (%) reduction in total abscess and inflammatory nodule counts (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 |
| --- | --- | --- |
| Part 1: Percentage of Participants Who Achieved HiSCR75 at Week 16 | HiSCR75 was defined as at least 75% reduction in total abscess and inflammatory nodule counts (AN count) with no increase in abscess count and no increase in draining fistula count relative to baseline. | Week 16 | 
| Part 1: Percentage of Participants Who Achieved HiSCR90 at Week 16 | HiSCR90 was defined as at least 90% reduction in total abscess and inflammatory nodule counts (AN count) with no increase in abscess count and no increase in draining fistula count relative to baseline. | Week 16 | 
| Part 1: Change From Baseline in the Abscess and Inflammatory Nodule (AN) Count at Week 16 | Change from baseline in the AN count as Week 16 was reported. Abscess and inflammatory nodule were counted for the hidradenitis suppurativa (HS) affected anatomical regions. The AN count is the sum of number of abscess and inflammatory nodules across anatomical regions. | Baseline, Week 16 | 
| Part 1: Change From Baseline in Number of Abscess at Week 16 | Change from baseline in number of abscess at Week 16 was reported. | Baseline, Week 16 | 
| Part 1: Change From Baseline in Number of Draining Fistula at Week 16 | Change from baseline in number of draining fistula at Week 16 was reported. Draining fistula was defined as fistulas that drain serous or purulent fluid, either spontaneously or by gentle palpation. | Baseline, Week 16 | 
| Part 1: Change From Baseline in Number of Inflammatory Nodules at Week 16 | Change from baseline in number of inflammatory nodules at Week 16 was reported. Inflammatory nodules arise from inflamed blood vessels (vasculitis) or adipose tissue (panniculitis). | Baseline, Week 16 | 
| Part 1: Change From Baseline in International Hidradenitis Suppurativa Severity Score (IHS4) at Week 16 | IHS4 was a dynamic severity assessment of HS. IHS4 score was arrived at by the number of nodules (multiplied by 1) plus the number of abscesses (multiplied by 2) plus the number of draining tunnels (multiplied by 4). A total score of 3 or less signifies mild, 4-10 signifies moderate and 11 or higher signifies severe disease. Higher scores indicate more severity. | Baseline up to Week 16 | 
| Part 1: 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 was 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. | Baseline, Week 16 | 
| Part 1: 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 in the past 24 hours based on HSSD was reported. | Baseline, Week 16 | 
| Serum Concentration of Bermekimab | Serum concentration of bermekimab was reported. As per planned analysis, this outcome measure was analyzed in a single arm for participants who received bermekimab from Week 0 to Week 36. | Weeks 0, 1, 4, 8, 12, 16, 20, 24, 28, 32, 36 | 
| Number of Participants With Antibodies to Bermekimab | Number of participants with antibodies to bermekimab was reported. As per planned analysis, this outcome measure was analyzed in a single arm for participants who received bermekimab from Week 0 to Week 36. | From baseline up to Week 36 |