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

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Terminated

CT.gov ID

NCT04791319

Collaborator

(none)

199

Enrollment

Locations

Arms

10.9

Actual Duration (Months)

4.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Dermatitis, Atopic	Drug: Placebo Drug: Bermekimab Drug: Dupilumab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

199 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 3, 2021

Actual Primary Completion Date :

Feb 2, 2022

Actual Study Completion Date :

Mar 31, 2022

Arms and Interventions

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: Placebo Placebo will be administered subcutaneously. Drug: Bermekimab Bermekimab will be administered subcutaneously. Other Names: JNJ-77474462
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: Placebo Placebo will be administered subcutaneously. Drug: Bermekimab Bermekimab will be administered subcutaneously. Other Names: JNJ-77474462 Drug: Dupilumab Dupilumab will be administered subcutaneously.

Outcome Measures

Primary Outcome Measures

Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (Greater Than or Equal to [>=] 75 Percent (%) Improvement From Baseline) for Efficacy of Bermekimab at Week 16 [Week 16]
The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of atopic dermatitis (AD). The EASI is a composite index with scores ranging from 0 to 72, with higher score indicative of more severe disease. Four AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation], and lichenification) will each be assessed for severity by the investigator or designee on a scale of "0" (absent) through "3" (severe). In addition, the area of AD involvement will be assessed as a percentage by body area of head, trunk, arms, and legs and converted to a score of 0 to 6.

Secondary Outcome Measures

Percentage of Participants With Both Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of 0 or 1 and a Reduction From Baseline of >=2 Points for Additional Assessments of Bermekimab at Week 16 [Week 16]
The vIGA-AD is an assessment instrument used in clinical studies to rate the severity of AD, based on a 5-point scale ranging from 0 (clear) to 4 (severe). The IGA score is selected using the morphological descriptors that best describe the overall appearance of the AD lesions at a given time point.
Percentage of Participants With Improvement (Reduction) of Eczema-Related Itch Numeric Rating Scale (NRS) Value of >=4 From Baseline to Week 16 Among Participants With a Baseline Itch Value >=4 for Additional Assessments of Bermekimab [Week 16]
Itch NRS is a 2-item participant-reported outcome that participants will use to rate the severity of their eczema-related itch daily. Participants will be asked the following question: Please rate the severity of your eczema-related itch at its worst in the past 24 hours on a 0 to 10 NRS ranging from 0 "none" to 10 "worst possible.
Percentage of Participants With EASI-90 (>=90% improvement in EASI from Baseline) for Additional Assessments of Bermekimab at Week 16 [Week 16]
The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher score indicative of more severe disease. Four AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation], and lichenification) will each be assessed for severity by the investigator or designee on a scale of "0" (absent) through "3" (severe). In addition, the area of AD involvement will be assessed as a percentage by body area of head, trunk, arms, and legs and converted to a score of 0 to 6.
Percentage of Participants With EASI-75 (Greater Than or Equal to [>=] 75 Percent (%) Improvement From Baseline) for Efficacy of Bermekimab Relative to Dupilumab at Week 16 [Week 16]
The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of atopic dermatitis AD. The EASI is a composite index with scores ranging from 0 to 72, with higher score indicative of more severe disease. Four AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation], and lichenification) will each be assessed for severity by the investigator or designee on a scale of "0" (absent) through "3" (severe). In addition, the area of AD involvement will be assessed as a percentage by body area of head, trunk, arms, and legs and converted to a score of 0 to 6.
Percentage of Participants With EASI-90 (>=90% improvement in EASI from Baseline) for Efficacy of Bermekimab Relative to Dupilumab at Week 16 [Week 16]
The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher score indicative of more severe disease. Four AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation], and lichenification) will each be assessed for severity by the investigator or designee on a scale of "0" (absent) through "3" (severe). In addition, the area of AD involvement will be assessed as a percentage by body area of head, trunk, arms, and legs and converted to a score of 0 to 6.
Percentage of Participants With Both vIGA-AD Score of 0 or 1 (on a 5-point scale) and a Reduction From Baseline of >=2 Points for Efficacy of Bermekimab Relative to Dupilumab at Week 16 [Week 16]
The vIGA-AD is an assessment instrument used in clinical studies to rate the severity of AD, based on a 5-point scale ranging from 0 (clear) to 4 (severe). The IGA score is selected using the morphological descriptors that best describe the overall appearance of the AD lesions at a given time point.
Percentage of participants With Improvement (Reduction) of Eczema-Related Itch NRS Value of >=4 From Baseline to Week 16 Among Participants With a Baseline Itch Value >=4 for Efficacy of Bermekimab Relative to Dupilumab [Week 16]
Itch NRS is a 2-item participant-reported outcome that participants will use to rate the severity of their eczema-related itch daily. Participants will be asked the following question: Please rate the severity of your eczema-related itch at its worst in the past 24 hours on a 0 to 10 NRS ranging from 0 "none" to 10 "worst possible.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Up to Week 36]
An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment.
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) [Up to Week 36]
A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Serum Bermekimab Concentration [Up to Week 36]
Serum bermekimab concentration will be measured.
Number of Participants with Anti-Bermekimab Antibodies [Up to Week 36]
Number of participants with anti-drug antibodies to bermekimab will be reported.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Janssen Research & Development, LLC

ClinicalTrials.gov Identifier:

NCT04791319

Other Study ID Numbers:

CR108932
2020-002587-31
77474462ADM2001

First Posted:

Mar 10, 2021

Last Update Posted:

Apr 14, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Dermatitis, Atopic

Dermatitis

Study Results

No Results Posted as of Apr 14, 2022