check_circleStudy Completed

Atopic dermatitis

Bayer Identifier:

22158

ClinicalTrials.gov Identifier:

NCT05656911

EudraCT Number:

2022-000520-38

EU CT Number:

Not Available
A study to learn how well the study treatment zabedosertib (BAY1834845) works and how safe it is compared to placebo in adult participants with moderate-to-severe atopic dermatitis

Trial purpose

Researchers are looking for a better way to treat atopic dermatitis (AD), an often long-lasting inflammation of the skin. Atopic dermatitis, also called eczema, is causing patches of skin to become swollen, red, cracked, and itchy.

The immune system helps protect the body from diseases. But sometimes the immune system can be too sensitive and overreact. This may then lead to allergies but also to skin conditions like atopic dermatitis.

The study treatment zabedosertib (BAY1834845) is currently under development for the treatment of atopic dermatitis and other inflammatory diseases. It works by reducing the activity of a protein called IRAK4. IRAK4 promotes the production and activation of a series of proteins that trigger inflammation reactions in the immune cells. By reducing the activity of IRAK4, the inflammation reactions are expected to be reduced.

The main purpose of the study is to learn how well zabedosertib works compared to placebo. A placebo is a treatment that looks like a medicine but does not have any medicine in it. How well it works means to find out the efficacy of zabedosertib. To answer this, the researchers will compare how many participants had 75% EASI score reduction after 12 weeks treatment between participants treated with zabedosertib and those treated with placebo. EASI represents Eczema Area and Severity Index (EASI). It is a tool for measuring the amount and severity of atopic dermatitis that a patient has on his or her body. The score ranges from 0-72, with 0 meaning clear skin and 72 meaning severe atopic dermatitis. In addition, the itch of the study participants and other tools for measuring the severity of atopic dermatitis will be assessed.

The secondary purpose of the study is to learn how safe it is compared to placebo. To know this, study team will compare how many participants having adverse events after taking study treatment between participants treated with zabedosertib and those treated with placebo.

In the study, participants will be randomly (by chance) assigned to receive zabedosertib or placebo. The participants from both treatment groups will take zabedosertib or placebo for up to 12 weeks.

The study consists of an up to 28-day screening period (Visits 1 and 2), a 12-week treatment period consisting of 5 visits (Visits 3 to 7), and a 4-week follow-up visits (Visits 8). Thus, the total study duration per participant will be 17 to 20 weeks (approximately 140 days).

During the study, the study team will:
•   take blood and urine samples
•   take skin samples (not obligatory for all patients)
•   check the participants’ disease area for assessment
•   provide participants device to record their disease status and to take pictures on their disease areas
•   have participants complete self-reported questionnaires
•   do physical examinations
•   examine heart health using ECG
•   check vital signs
•   ask the participants questions about how they are feeling and what events they are having.

An adverse event is any problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.

At 28 days after the participants take their last treatment, the study team will check if participants have any events that might be related to the study treatment. This will be the last visit for the study.

Key Participants Requirements

Sex

All

Age

18 - 65 Years
  • - 18 to 65 years of age inclusive, at the time of signing the informed consent.
    - Diagnosis of atopic dermatitis (AD) for ≥ 1 year at the screening visit.
    - Moderate-to-severe AD at randomization visit as defined by
     -- Eczema Area and Severity Index (EASI) score ≥ 16,
     -- Body surface area (BSA) affected by AD ≥ 10%,
     -- Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score ≥ 3, and
     -- Peak Pruritus 0-10 numerical rating scale (NRS) ≥ 4 (average score of the daily scores of the 7 days before randomization, with ≥ 4 scores required).
    - Documented history (within 6 months prior to the first screening visit) of inadequate response to treatment with topical corticosteroids (TCS), or if TCS are medically not advisable (e.g., due to important side effects or safety risks).
    - Stable amount of emollient applied to skin over the whole body twice daily for at least the 7 consecutive days before the randomization visit
    - Body mass index (BMI) within the range of 18.5 to 35.0 kg/m^2 (inclusive) at screening (Visit 1) and randomization visits.
    - Women of childbearing potential and male subjects able to father children must agree to use adequate contraception when sexually active.
  • - History of any major surgery within 8 weeks prior to screening or scheduled (elective) surgery, planned hospitalization and/or planned dental treatment during the study that could constitute a risk when participating in a study.
    - Severe invasive infections in medical history and/or active clinically significant viral, bacterial, fungal, or parasitic infection (systemic or severe skin infection) ≤ 3 months prior to the randomization visit.
    - A presence of uncontrolled condition including cardiovascular, respiratory, hepatic renal, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other unstable illness that, in the opinion of the investigator, could constitute a risk when taking investigational product, study conduct or could interfere with the interpretation of data.
    - Known immunodeficiency disorder or immunocompromised state or, in the opinion of the investigator, unacceptable risk for participating in the study.
    - Use of topical treatments for AD within 7 days before the randomization visit.
    - Systemic immunosuppressive/ immunomodulating therapy or phototherapy within 4 weeks before the randomization visit.
    - Therapy with biologic drugs within 5 half-lives of the biologic drug
    - Known hypersensitivity to the study drug

Trial summary

Enrollment Goal
77
Trial Dates
December 2022 - January 2024
Phase
Phase 2
Could I Receive a placebo
Yes
Products
Zabedosertib (BAY1834845)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Hautarztpraxis Prof. Dr. med. Christian TermeerStuttgart, 70499, Germany
Completed
Charité - Universitätsmedizin BerlinBerlin, 10117, Germany
Completed
Whipps Cross University Hospital - Clinical Research UnitLeytonstone, E11 1NR, United Kingdom
Completed
Medicines Evaluation UnitWythenshawe, M23 9QZ, United Kingdom
Completed
Beth Israel Deaconess Medical Center - DermatologyBoston, 02115, United States
Completed
University of Cincinnati College of Medicine - DermatologyCincinnati, 45219, United States
Completed
Arlington Research Center, Inc. | Arlington, TXArlington, 76011, United States
Completed
NorthShore University HealthSystem | Skokie Hospital - Dermatology DepartmentSkokie, 60077, United States
Completed
Hôpital Saint LouisPARIS, 75010, France
Completed
Centre Hospitalier Universitaire Nice | L'Archet Hospital - Dermatology DepartmentNICE CEDEX 3, 6202, France
Completed
Clinique BezannesBezannes, 51430, France
Completed
Dermal NZOZ Sp Osrodek Dermatologiczny Bialystok-PodlasieBialystok, 15-453, Poland
Completed
Centrum Nowoczesnych Terapii Dobry LekarzKrakow, 31-011, Poland
Completed
Royalderm Agnieszka NawrockaWarszawa, 02-962, Poland
Completed
Santa Sp. z o.o.Lodz, 90-302, Poland
Completed
Humanitas Research Hospital | Cardio Center - Clinical, Interventional Cardiology and Coronary CareMilano, 20089, Italy
Completed
Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilano, 20122, Italy
Completed
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di CataniaCatania, 95123, Italy
Completed
University Hospital Of FerraraFerrara, 44124, Italy
Completed
Dermamedica s.r.o.Nachod, 547 01, Czech Republic
Completed
Clintrial s.r.o.Praha 10, 100 00, Czech Republic
Completed
PRAGLANDIAPraha 5, 150 00, Czech Republic

Primary Outcome

  • Achievement of 75% reduction from baseline in the Eczema Area and Severity Index (EASI 75 response) at Week 12 (Day 84)
    The endpoint was the composite variable defined as follows: - an EASI 75 response at Week 12 (Day 84), - no stop of study intervention for reasons related to lack of efficacy, - no rescue medication use during the 4 weeks before Day 84 and - no use of systemic atopic dermatitis (AD) treatment. The main estimand was the difference in the proportion of responders between treatment groups in adults with moderate-to-severe atopic dermatitis where use of topical rescue medication from Day 56 (Visit 6) onwards, use of systemic standard of care for AD and discontinuation of treatment due to lack of efficacy are handled as non-response (composite strategy). The estimand was regardless of use of rescue medication before Day 56 (Visit 6), regardless of non-compliance with emollients, and had treatment not been discontinued due to other reasons not related to lack of efficacy. Bayesian analysis according to estimand is presented.
    date_rangeTime Frame:
    Week 12 (Day 84)

Secondary Outcome

  • Percent change from baseline in EASI at Week 12 (Day 84)
    The EASI is a ClinRO assessing the extent of AD at four body regions by measuring the average severity of four clinical signs at each body region, each on a scale of 0 to 3. The minimum EASI score is 0 and the maximum EASI score is 72, with a higher score indicating worse severity of AD. The main estimand was based on the same strategies to address intercurrent events as described above for the primary endpoint. The mean difference between the treatment arms was used as summary measure.
    date_rangeTime Frame:
    Baseline and Week 12 (Day 84)
  • Achievement of EASI 50 response at Week 12 (Day 84)
    The EASI is a ClinRO assessing the extent of AD at four body regions by measuring the average severity of four clinical signs at each body region, each on a scale of 0 to 3. The minimum EASI score is 0 and the maximum EASI score is 72, with a higher score indicating worse severity of AD. EASI 50 corresponds to the achievement of 50% reduction from baseline in EASI. The main estimand was calculated similarly as for EASI 75. Bayesian analysis according to estimand is presented.
    date_rangeTime Frame:
    Week 12 (Day 84)
  • Achievement of EASI 90 response at Week 12 (Day 84)
    The EASI is a ClinRO assessing the extent of AD at four body regions by measuring the average severity of four clinical signs at each body region, each on a scale of 0 to 3. The minimum EASI score is 0 and the maximum EASI score is 72, with a higher score indicating worse severity of AD. EASI 90 corresponds to the achievement of 90% reduction from baseline in EASI. The main estimand was calculated similarly as for EASI 75. Bayesian analysis according to estimand is presented.
    date_rangeTime Frame:
    Week 12 (Day 84)
  • Achievement of a vIGA-AD response (score 0 or 1 and ≥ 2 points improvement) at Week 12 (Day 84)
    vIGA-AD stands for validated Investigator Global Assessment for Atopic Dermatitis. The vIGA-AD is a 1-item static ClinRO using a 5-point scale from 0 (clear) to 4 (severe) based on 4 clinical features of AD lesions: erythema, induration/papulation, lichenification, and oozing/crusting, and takes extent of disease into account. The main estimand was calculated similarly as for EASI 75. Bayesian analysis according to estimand is presented.
    date_rangeTime Frame:
    Week 12 (Day 84)
  • Absolute change from baseline in body surface area (BSA) affected by atopic dermatitis (AD) at Week 12 (Day 84)
    BSA affected by AD was assessed for each section of the body, e.g. using the rule of nines. The possible highest score for each region is: Head and neck - 9%; Anterior trunk - 18%; Back - 18%; Upper limbs - 18%; Lower limbs - 36%; Genitals - 1%. Affected BSA was reported as a percentage of all major body sections combined. The main estimand was based on the same strategies to address intercurrent events as described above for the primary endpoint. The mean difference between the treatment arms was used as summary measure.
    date_rangeTime Frame:
    Baseline and Week 12 (Day 84)
  • Achievement of a ≥ 4 point-improvement (reduction) in the weekly average of the Peak Pruritus 0-10 NRS score from baseline to Week 12 (Day 84) for participants with Peak Pruritus 0-10 NRS score ≥ 4 at baseline
    NRS stands for numerical rating scale. The Peak Pruritus 0-10 NRS is a single patient-reported item designed to measure peak pruritus (itch), or ‘worst’ itch, over the previous 24 h based on the following question: ‘On a scale of 0 to 10, with 0 being “no itch” and 10 being “worst itch imaginable”, how would you rate your itch at the worst moment during the previous 24 hours?’. ≥ 4 points reduction of the Peak Pruritus 0-10 NRS is considered a clinically relevant within-person response. NRS was assessed on a daily basis and the average over the last 7 days before the visit day was used for analysis. The main estimand was calculated similarly as for EASI 75. Bayesian analysis according to estimand is presented.
    date_rangeTime Frame:
    Baseline and Week 12 (Day 84)
  • Absolute values of weekly average of the Peak Pruritus 0-10 numerical rating scale (NRS) score at Week 12 (Day 84)
    The Peak Pruritus 0-10 NRS is a single patient-reported item designed to measure peak pruritus (itch), or ‘worst’ itch, over the previous 24 h based on the following question: ‘On a scale of 0 to 10, with 0 being “no itch” and 10 being “worst itch imaginable”, how would you rate your itch at the worst moment during the previous 24 hours?’. ≥ 4 points reduction of the Peak Pruritus 0-10 NRS is considered a clinically relevant within-person response. NRS was assessed on a daily basis and the average over the last 7 days before the visit day was used for analysis. The main estimand was based on the same strategies to address intercurrent events as described above for the primary endpoint.
    date_rangeTime Frame:
    Week 12 (Day 84)
  • Percent change of weekly average of the Peak Pruritus 0-10 NRS score from baseline at Week 12 (Day 84)
    The Peak Pruritus 0-10 NRS is a single patient-reported item designed to measure peak pruritus (itch), or ‘worst’ itch, over the previous 24 h based on the following question: ‘On a scale of 0 to 10, with 0 being “no itch” and 10 being “worst itch imaginable”, how would you rate your itch at the worst moment during the previous 24 hours?’. ≥ 4 points reduction of the Peak Pruritus 0-10 NRS is considered a clinically relevant within-person response. NRS was assessed on a daily basis and the average over the last 7 days before the visit day was used for analysis. The main estimand was based on the same strategies to address intercurrent events as described above for the primary endpoint. ANCOVA analysis according to estimand is presented.
    date_rangeTime Frame:
    Baseline and Week 12 (Day 84)
  • Frequency and severity of treatment-emergent adverse events (TEAEs)
    date_rangeTime Frame:
    From first treatment with the study intervention until 7 days after the last intake of study intervention (approximately up to 91 days)

Trial design

A randomized, placebo-controlled, double-blind, parallel-group, multicenter Phase 2a study to investigate efficacy and safety of zabedosertib (BAY 1834845) for the treatment of adult patients with moderate-to-severe atopic dermatitis
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
N/A
Assignment
Parallel Assignment
Trial Arms
2

Additional Information

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