Clinical trial NCT04021862: A Study to Evaluate the Safety and Efficacy of Bermekimab in Patients With Moderate to Severe Atopic Dermatitis
Official title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Bermekimab in Patients With Moderate to Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Dermatitis
Eczema
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-07-16
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: A Study to Evaluate the Safety and Efficacy of Bermekimab in Patients With Moderate to Severe Atopic Dermatitis

Detailed description: This is a phase II, randomized, double-blind, placebo-controlled study of bermekimab in patients with moderate to severe atopic dermatitis. The primary objective of the study is to analyze the safety and efficacy of different dose regimens of bermekimab compared to placebo treatment in adult patients with moderate-to-severe AD. The study is multicenter and will consist of three groups:

Treatment Arm 1: Bermekimab every week (qw)

Treatment Arm 2: Bermekimab every other week (q2w)

Arm 3 (Placebo): Placebo every week (qw)

Eligibility criteria: Inclusion Criteria:

* Male or female, at least 18 years
* Willing and able to attend all clinic visits and comply with study-related procedures
* Participant can understand and complete study-related questionnaires
* Written informed consent provided by the participant
* Chronic atopic dermatitis present for at least 3 years
* Eczema Area and Severity Index Score (EASI) score greater than or equal to (\>=) 16 at screening and baseline visits
* Investigators Global Assessment (IGA) \>= 3 at screening and baseline visits
* Baseline pruritis numerical rating scale average score for maximum intensity of at least 3, based on the average of daily pruritis numerical rating scale scores for maximum itch intensity reported during the 7 days prior to randomization
* Has applied a stable dose of topical moisturizer twice daily for at least 7 consecutive days immediately prior to the baseline visit and is willing to continue this regimen on a daily basis for the duration of the study
* \>= 10 percent (%) body surface area (BSA) of Atopic Dermatitis (AD) involvement at screening and baseline visits
* Documented recent history (within 6 months prior to screening) of inadequate response to treatment with topical medications, or participants for whom topical treatments are medically inadvisable (because of important side effects or safety risks): (a) Inadequate response is defined as failure to achieve and maintain remission or a low disease activity state (comparable to an IGA score of 0-2), despite treatment with a daily regimen of topical corticosteroids of medium to higher potency (with or without topical calcineurin inhibitors as appropriate), applied for at least 28 days or for the maximum duration recommended by the product prescribing information, whichever is shorter; (b) Participants with documented systemic treatment for atopic dermatitis in the preceding 6 months are also considered to be inadequate responders to topical treatments and are potentially eligible for treatment with MABp1, after appropriate washout; (c) Important side effects or risks are those that outweigh the potential treatment benefits, and include: intolerance to treatment, hypersensitivity reactions, significant skin atrophy, and adverse systemic effects; and (d) Acceptable documentation includes contemporaneous chart notes that record topical medication prescription and treatment outcome, or investigator documentation based on communication with the participant's treating physician.

Exclusion Criteria:

* Participants has been treated for AD with any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives (whichever is longer) of the drug prior to baseline
* Treatment with bermekimab at any time in the past
* Treatment with immunosuppressive/immunomodulatory drugs or phototherapy for atopic dermatitis within 4 weeks of baseline, or any condition that, in the opinion of the investigator, is likely to require such treatment(s) during the first 4 weeks of study treatment
* Treatment with topical corticosteroids or topical calcineurin inhibitors for the treatment of AD within 14 days prior to baseline
* Treatment with biologics as follows: (a) Any cell-depleting agents including, but not limited to, rituximab, within 5 half-lives (if known) or 30 days prior to baseline visit, or until lymphocyte count returns to normal, whichever is longer; (b) Other biologics: within 5 half-lives (if known) or 30 days prior to baseline visit, whichever is longer
* Initiation of treatment of atopic dermatitis with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period (participants may continue to use stable doses of such moisturizers if initiated before the screening visit)
* Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening visit
* Planned or anticipated use of any prohibited medications and procedures during study treatment
* Treatment with a live (attenuated) vaccine within 30 days prior to the screening visit
* Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks prior to the baseline visit, or superficial skin infections within 1 week prior to the baseline visit
* Known or suspected history of immunosuppression, including history of invasive opportunistic infections (for example, tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis, aspergillosis) despite infection resolution; or unusually frequent, recurrent, or prolonged infections, per investigator judgment
* History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening
* Positive for hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody at the screening visit
* At baseline, presence of any conditions listed as criteria for study drug discontinuation
* Presence of skin comorbidities that may interfere with study assessments
* History of malignancy within 5 years before the screening visit, except completely treated in situ carcinoma of the cervix, and completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin diagnosed active endoparasitic infections; suspected or high risk of endoparasitic, unless clinical and (if necessary) laboratory assessments have ruled out active infection before randomization
* Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the Participant's participation in the study. Examples include, but are not limited to, participants with short life expectancy, participants with uncontrolled diabetes (HbA1c \>= 9%), participants with cardiovascular conditions (for example, stage III or IV cardiac failure according to the New York Heart Association classification), severe renal conditions (for example, participants on dialysis), hepato-biliary conditions (for example, Child-Pugh class B or C), neurological conditions (for example, demyelinating diseases), active major autoimmune diseases (for example, lupus, inflammatory bowel disease, rheumatoid arthritis, etc.), other severe endocrinological, gastrointestinal, metabolic, pulmonary or lymphatic diseases. The specific justification for participants excluded under this criterion will be noted in study documents (chart notes, case report forms \[CRFs\], etc.)
* Planned or anticipated major surgical procedure during the participant's participation in this study
* Membership of the investigational team or his/her immediate family
* Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study
* Women unwilling to use adequate birth control, if of reproductive potential and sexually active. Adequate birth control is defined as consistent practice of an effective and accepted method of contraception throughout the duration of the study and for 120 days after the last dose of study drug. These methods include hormonal contraceptives, intrauterine device, double barrier contraception (that is, condom + diaphragm), or male partner with a documented vasectomy
* History of severe allergic or anaphylactic reactions to monoclonal antibodies
* Any other medical or psychological condition (including relevant laboratory abnormalities at screening) that, in the opinion the investigator, may suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study participant as a result of his/her participation in the study, may make participant's participation unreliable, or may interfere with study assessments. The specific justification for participant excluded under this criterion will be noted in study documents (chart notes, case report forms, etc.)

Primary outcomes:
measure: Percentage of Participants Achieving Eczema Area and Severity Index-75 (EASI-75) Response at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants Achieving >=4 Point Improvement (Reduction From Baseline) in Weekly Average Peak (Worst) Daily Pruritus (Itch) Numeric Rating Scale (NRS) Score From Baseline at Week 4, 8, 12, 16 and 32 Among Participants With Baseline Score >=4
timeFrame: Weeks 4, 8, 12, 16 and 32
measure: Percentage of Participants Achieving >= 4 Point Improvement (Reduction From Baseline) in Weekly Average of Average Daily Pruritis (Itch) NRS Score From Baseline at Weeks 4, 8, 12, 16 and 32 Among Participants With a Baseline Score >=4
timeFrame: Weeks 4, 8, 12, 16 and 32
measure: Percentage of Participants Achieving >=4 Improvement (Reduction From Baseline) in Weekly Average Peak (Worst) Daily Skin Pain NRS Score From Baseline at Weeks 4, 8, 12, 16 and 32 Among Participants With a Baseline Score >=4
timeFrame: Weeks 4, 8, 12, 16 and 32
measure: Percentage of Participants Achieving >=4 Improvement (Reduction From Baseline) in Weekly Average of Average Daily Skin Pain NRS Score From Baseline at Weeks 4, 8, 12, 16 and 32 Among Participants With a Baseline Score >=4
timeFrame: Weeks 4, 8, 12, 16 and 32
measure: Percentage of Participants Achieving EASI-75 Response at Weeks 4, 8, 12, and 32
timeFrame: Weeks 4, 8, 12, and 32
measure: Percentage of Participants With an Investigators Global Assessment (IGA) Score of 0 or 1 and a Reduction From Baseline of >=2 Points at Week 16
timeFrame: Week 16
measure: Percentage of Participants Achieving EASI-90 Response at Weeks 12, 16, and 32
timeFrame: Weeks 12, 16, and 32
measure: Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 8, 12, 16, and 32
timeFrame: Baseline, Weeks 8, 12, 16 and 32
measure: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) (Anxiety) Score at Weeks 8, 12, 16, and 32
timeFrame: Baseline, Weeks 8,12,16 and 32
measure: Change From Baseline in HADS (Depression) Score at Weeks 8, 12, 16, and 32
timeFrame: Baseline, Weeks 8,12,16 and 32
measure: Change From Baseline in Patient Oriented Eczema Measure (POEM) Scores at Weeks 8, 12, 16, and 32
timeFrame: Baseline, Weeks 8, 12, 16, and 32
measure: Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Total Score at Weeks 8, 12, 16, and 32.
timeFrame: Baseline to Weeks 8, 12, 16 and 32
measure: Change From Baseline in Global Individual Signs Score (GISS) at Weeks 8, 12, 16, and 32.
timeFrame: Baseline, Weeks 8,12,16 and 32
Other outcomes:
Locations:
city: Huntington Beach
country: United States
facility: Beach Clinical Research Inc
state: California
city: Coral Gables
country: United States
facility: Florida Academic Dermatology Centers
state: Florida
city: Doral
country: United States
facility: Doral Medical Research
state: Florida
city: Miami
country: United States
facility: Floridian Research Institute
state: Florida
city: Miami
country: United States
facility: Florida International Medical Research
state: Florida
city: Miami
country: United States
facility: Premier Research Associate, Inc
state: Florida
city: Orlando
country: United States
facility: CNS HealthCare
state: Florida
city: Tampa
country: United States
facility: Avita Clinical Research
state: Florida
city: Tampa
country: United States
facility: Forcare Clinical Research Inc
state: Florida
city: Sandy Springs
country: United States
facility: Advanced Medical Research
state: Georgia
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group
state: Indiana
city: West Lafayette
country: United States
facility: Randall Dermatology & Cosmetic Surgery
state: Indiana
city: Troy
country: United States
facility: Revival Research Institute LLC
state: Michigan
city: Columbus
country: United States
facility: ClinOhio Research Services
state: Ohio
city: Milan
country: United States
facility: Helios Clinical Research, LLC
state: Tennessee
city: San Antonio
country: United States
facility: Progressive Clinical Research
state: Texas
city: Richmond
country: United States
facility: Dominion Medical Associates, Inc.
state: Virginia
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: