A Study of Bermekimab (JNJ-77474462) in the Treatment of Participants With Moderate to Severe Atopic Dermatitis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy and safety of bermekimab in participants with moderate to severe atopic dermatitis (AD).

Official Title
-----------------
A Phase 2b, Multicenter, Randomized, Placebo- and Active-comparator-controlled, Double-blind Study to Evaluate the Safety and Efficacy of Bermekimab (JNJ-77474462) for the Treatment of Participants With Moderate to Severe Atopic Dermatitis

Conditions
-----------------
Dermatitis, Atopic

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Bermekimab
* Drug: Dupilumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Be otherwise healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiograms (ECGs) performed at screening. Any abnormalities, must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and initialed by the investigator Have atopic dermatitis (AD) for at least 1 year (365 days) prior to the first administration of study intervention as determined by the investigator through participant interview and/or review of the medical history Have a history of inadequate response to treatment for AD with topical medications or for whom topical treatments are otherwise medically inadvisable (example [eg], due to important side effects or safety risks) Be considered, in the opinion of the investigator, a suitable candidate for dupilumab (DUPIXENT) therapy according to their country's approved DUPIXENT product labeling Have an eczema area and severity index (EASI) score greater than or equal (>=) to 16 at screening and at baseline Have an investigator global assessment (IGA) score >=3 and involved body surface area (BSA) >=10 percent (%) at screening and baseline 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 (eg, unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiac hospitalization within the last 3 months Has or has had a serious infection (eg, sepsis, pneumonia, or pyelonephritis), or has been hospitalized or received intravenous (IV) antibiotics for an infection during the 2 months before screening Has or has had herpes zoster within the 2 months before screening Has a history of being human immunodeficiency virus (HIV) antibody-positive, or tests positive for HIV at screening

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 |
| --- | --- |
| Placebo Comparator: Group 1: Placebo<br>Participants will receive subcutaneous (SC) placebo once a week (qw) through Week 15. At Week 16, participants will crossover to receive SC bermekimab Dose 2 qw through Week 31. | Drug: Placebo<br>* Placebo will be administered subcutaneously.<br>Drug: Bermekimab<br>* Bermekimab will be administered subcutaneously.<br>* Other names: JNJ-77474462;|
| Experimental: Group 2: Bermekimab<br>Participant will receive SC bermekimab Dose 1 qw from Week 0 through Week 31. | Drug: Bermekimab<br>* Bermekimab will be administered subcutaneously.<br>* Other names: JNJ-77474462;|
| Experimental: Group 3: Bermekimab<br>Participants will receive SC bermekimab Dose 2 qw from Week 0 through Week 15. At Week 16, participants who achieve an eczema area and severity index (EASI)-75 response (responders) will be rerandomized either to continue to receive bermekimab Dose 2 qw, or to receive bermekimab Dose 1 qw, through Week 31 and participants who do not achieve an EASI-75 response (non responders) will continue to receive bermekimab Dose 2 qw through Week 31. | Drug: Bermekimab<br>* Bermekimab will be administered subcutaneously.<br>* Other names: JNJ-77474462;|
| Active Comparator: Group 4: Dupilumab<br>Participants will receive a loading dose of SC dupilumab Dose 1 at Week 0, SC placebo every two week (q2w) from Week 1 through Week 15 and then dupilumab Dose 2 q2w from Week 2 through Week 14. At Week 16, participants who achieve EASI-75 response (dupilumab responders) will continue on dupilumab Dose 2 q2w through Week 30 and placebo q2w from Week 17 through Week 31. Participants who do not achieve an EASI-75 response (dupilumab non-responders) will receive placebo qw from Week 16 through Week 18 (washout period) and bermekimab Dose 2 qw from Week 19 through Week 31. | Drug: Placebo<br>* Placebo will be administered subcutaneously.<br>Drug: Bermekimab<br>* Bermekimab will be administered subcutaneously.<br>* Other names: JNJ-77474462;Drug: Dupilumab<br>* Dupilumab will be administered subcutaneously.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Eczema Area and Severity Index-75 (EASI-75) (Greater Than or Equal to [>=] 75 Percent [%] Improvement From Baseline) at Week 16 | Percentage of participants achieving EASI-75 at Week 16 were reported. EASI-75 response is defined as at least 75% improvement from baseline in EASI total score. The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration/papulation, excoriation and lichenification on 4 anatomic regions of the body: head/neck, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 and a Reduction From Baseline of >=2 Points at Week 16 | Percentage of participants achieving vIGA-AD at Week 16 were reported. It is an assessment instrument used in clinical studies to rate the severity of AD, based on a 5-point scale ranging from 0, where 0=Clear: No inflammatory signs of AD; 1=almost clear: Barely perceptible erythema, induration/papulation and/or lichenification; 2=mild: Slight but definite erythema, induration/papulation and/or minimal lichenification. No oozing or crusting; 3=moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, oozing or crusting may be present and 4=severe: Marked erythema, induration/papulation and/or lichenification; Oozing or crusting may be present. Higher score indicated more severity of AD. | Week 16 | 
| Percentage of Participants With Improvement (Reduction From Baseline) in Eczema-Related Itch Numeric Rating Scale (NRS) of Score >=4 at Week 16 Among Participants With a Baseline Itch Value >=4 | Percentage of participants with improvement (reduction from baseline) in eczema-related itch NRS of score >=4 at Week 16 among participants with a baseline itch value >=4 were reported. The eczema skin pain and Itch NRS is a 2-item patient-reported outcome that participants used to rate the severity of their eczema-related skin pain and eczema related itch daily. Participants were asked the following questions: Please rate the severity of your eczema-related skin pain at its worst in the past 24 hours; and please rate the severity of your eczema-related itch at its worst in the past 24 hours. Each item was on a 0 to 10 NRS ranging from 0 none to 10 worst possible and were scored separately. Higher score indicated more severity. | Week 16 | 
| Percentage of Participants Achieving EASI-90 (>= 90% Improvement in EASI From Baseline) at Week 16 | Percentage of participants achieving EASI-90 at Week 16 were reported. EASI-90 response is defined as at least 90% improvement from baseline in EASI total score. The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration/papulation, excoriation and lichenification on 4 anatomic regions of the body: head/neck, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. | Week 16 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs were AEs with onset during the intervention period or that were a consequence of a pre-existing condition that has worsened since baseline. AEs are presented by individual dose received by participants during placebo-controlled period and by responders individual dose received during active treatment period. | Up to Week 36 | 
| Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) | An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. Any SAE with onset during the intervention period or that were a consequence of a pre-existing condition that has worsened since baseline was considered to be TESAEs. AEs are presented by individual dose received by participants during placebo-controlled period and active treatment period. | Up to Week 36 | 
| Serum Bermekimab Concentration Over Time | Serum bermekimab concentration over time were reported. Data are presented by individual dose of investigational medicinal product received by participants during active treatment period as preplanned in protocol. | Pre-dose at Week 0, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, and Week 36 | 
| Number of Participants With Anti-Bermekimab Antibodies | Number of participants with anti-bermekimab antibodies were reported. Data are presented by individual dose of investigational medicinal product received by participants during active treatment period as preplanned in protocol. | Up to Week 36 |