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

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

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

Study Overview

• Status: Terminated
• Conditions: Dermatitis, Atopic
• Intervention / Treatment: Drug: Bermekimab; Drug: Placebo; Drug: Dupilumab

• Study Type: Interventional
• Enrollment (Actual): 199
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4X7
    • Centre De Recherche Dermatologique Du Quebec Metropolitan
  • Alberta
    • Calgary, Alberta, Canada, T2J 7E1
      • Dermatology Research Institute Inc.
  • Ontario
    • Markham, Ontario, Canada, L3P 1X3
      • Lynderm Research Inc.
    • Mississauga, Ontario, Canada, L4Y 4C5
      • DermEdge Research
    • Niagara Falls, Ontario, Canada, L2H 1H5
      • Allergy Research Canada Inc.
  • Quebec
    • Montreal, Quebec, Canada, H2H2B5
      • Innovaderm Research Inc.
• Germany
  • Bad Bentheim, Germany, 48455
    • Fachklinik Bad Bentheim
  • Berlin, Germany, 10789
    • ISA - Interdisciplinary Study Association GmbH
  • Frankfurt/ Main, Germany, 60590
    • Goethe Universität Frankfurt
  • Hamburg, Germany, 22391
    • MENSINGDERMA research GmbH
  • Hamburg, Germany, 20537
    • TFS Trial Form Support GmbH
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Langenau, Germany, 89129
    • Praxis Dr. med. Beate Schwarz - Germany
  • Mahlow, Germany, 15831
    • Hautarztpraxis
• Japan
  • Obihiro-shi, Japan, 080-0013
    • Takagi Clinic
  • Osaka Fu, Japan, 593-8324
    • Kume Clinic
  • Sapporo, Japan, 060-0063
    • Sapporo Skin Clinic
• Poland
  • Czestochowa, Poland, 42-200
    • NZOZ Przychodnia Specjalistyczna Medica
  • Lodz, Poland, 90-242
    • Centrum Terapii Wspolczesnej J. M. Jasnorzewska Spolka Komandytowo-Akcyjna
  • Osielsko, Poland, 86031
    • DermoDent Centrum Medyczne Aldona Czajkowska Rafał Czajkowski s.c.
  • Warszawa, Poland, 02-953
    • Klinika Ambroziak Estederm Sp. z o.o
  • Warszawa, Poland, 02962
    • Royalderm Agnieszka Nawrocka
  • Wroclaw, Poland, 50566
    • Centrum Medyczne Matusiak w CITYCLINICPrzychodnia Lekarsko-Psychologiczna Matusiak Spółka Partnerska
  • Wrocław, Poland, 51-685
    • WroMedica I.Bielicka, A.Strzałkowska s.c.
• United States
  • California
    • Los Angeles, California, United States, 90025
      • California Allergy & Asthma Medical Group Inc.
    • Santa Ana, California, United States, 92705
      • Wolverine Clinical Trials
  • Florida
    • Orange Park, Florida, United States, 32073
      • Park Avenue Dermatology
    • Tampa, Florida, United States, 33613
      • ForCare Clinical Research, Inc.
  • Illinois
    • Rolling Meadows, Illinois, United States, 60008
      • Arlington Dermatology
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin Clinical Research Group
  • Michigan
    • Warren, Michigan, United States, 48088
      • Grekin Skin Institute
  • New Jersey
    • East Windsor, New Jersey, United States, 08520
      • Psoriasis Treatment Center of Central New Jersey
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Ohio State University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Clinical Partners
  • Texas
    • Arlington, Texas, United States, 76011
      • Arlington Center for Dermatology
    • Pflugerville, Texas, United States, 78660
      • Austin Institute for Clinical Research
    • San Antonio, Texas, United States, 78213
      • Progressive Clinical Research
    • Webster, Texas, United States, 77598
      • Center for Clinical Studies
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Clinical Research
  • Washington
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 1: Placebo; 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: Bermekimab; Bermekimab will be administered subcutaneously.; Other Names: JNJ-77474462; Drug: Placebo; Placebo will be administered subcutaneously.
Experimental: Group 2: Bermekimab; Participant will receive SC bermekimab Dose 1 qw from Week 0 through Week 31.	Drug: Bermekimab; Bermekimab will be administered subcutaneously.; Other Names: JNJ-77474462
Experimental: Group 3: Bermekimab; 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; Bermekimab will be administered subcutaneously.; Other Names: JNJ-77474462
Active Comparator: Group 4: Dupilumab; 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: Bermekimab; Bermekimab will be administered subcutaneously.; Other Names: JNJ-77474462; Drug: Placebo; Placebo will be administered subcutaneously.; Drug: Dupilumab; Dupilumab will be administered subcutaneously.

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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2021
• Primary Completion (Actual): February 2, 2022
• Study Completion (Actual): March 31, 2022

Study Registration Dates

• First Submitted: March 9, 2021
• First Submitted That Met QC Criteria: March 9, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 1, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Dermatitis, Atopic
• Other Study ID Numbers: CR108932; 2020-002587-31 (EudraCT Number); 77474462ADM2001 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No