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

NCT05656911 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 221582022-000520-38
• Study Type: interventional
• Target: 77
• Locations: 7 countries
• Sites: 22

Brief Summary

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.

Conditions

Atopic Dermatitis

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 12 (Day 84)

Secondary Outcomes (9)

• Percent Change From Baseline in EASI at Week 12 (Day 84)

  Baseline and Week 12 (Day 84)

• Achievement of EASI 50 Response at Week 12 (Day 84)

  Week 12 (Day 84)

• Achievement of EASI 90 Response at Week 12 (Day 84)

  Week 12 (Day 84)

• Achievement of a vIGA-AD Response (Score 0 or 1 and ≥ 2 Points Improvement) at Week 12 (Day 84)

  Week 12 (Day 84)

• Absolute Change From Baseline in Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 12 (Day 84)

  Baseline and Week 12 (Day 84)

Study Arms (2)

Zabedosertib

EXPERIMENTAL

Participants will receive zabedosertib for up to 12 weeks (84 days).

Drug: Zabedosertib (BAY1834845)

Matching placebo to zabedosertib

PLACEBO COMPARATOR

Participants will receive placebo to zabedosertib for up to 12 weeks (84 days).

Drug: Placebo to zabedosertib (BAY1834845)

Interventions

Zabedosertib (BAY1834845) DRUG

Oral administration, two times a day

Zabedosertib

Placebo to zabedosertib (BAY1834845) DRUG

Oral administration, two times a day

Matching placebo to zabedosertib

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (22)

NorthShore University HealthSystem | Skokie Hospital - Dermatology Department

Skokie, Illinois, 60077, United States

Location

Beth Israel Deaconess Medical Center - Dermatology

Boston, Massachusetts, 02115, United States

Location

University of Cincinnati College of Medicine - Dermatology

Cincinnati, Ohio, 45219, United States

Location

Arlington Research Center, Inc. | Arlington, TX

Arlington, Texas, 76011, United States

Location

Dermamedica s.r.o.

Náchod, Královéhradecký kraj, 547 01, Czechia

Location

Clintrial s.r.o.

Prague, 100 00, Czechia

Location

Praglandia

Prague, 150 00, Czechia

Location

Clinique Bezannes

Bezannes, 51430, France

Location

Centre Hospitalier Universitaire Nice | L'Archet Hospital - Dermatology Department

Nice, 6202, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Hautarztpraxis Prof. Dr. med. Christian Termeer

Stuttgart, Baden-Wurttemberg, 70499, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

A.O.U. di Ferrara

Ferrara, Emilia-Romagna, 44124, Italy

Location

Humanitas Research Hospital | Cardio Center - Clinical, Interventional Cardiology and Coronary Care

Milan, Lombardy, 20089, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania

Catania, Sicily, 95123, Italy

Location

Dermal NZOZ Sp Osrodek Dermatologiczny Bialystok-Podlasie

Bialystok, 15-453, Poland

Location

Centrum Nowoczesnych Terapii Dobry Lekarz

Krakow, 31-011, Poland

Location

Santa Sp. z o.o.

Lodz, 90-302, Poland

Location

Royalderm Agnieszka Nawrocka

Warsaw, 02-962, Poland

Location

Whipps Cross University Hospital - Clinical Research Unit

Leytonstone, London, E11 1NR, United Kingdom

Location

Medicines Evaluation Unit

Wythenshawe, Manchester, M23 9QZ, United Kingdom

Location

Related Publications (1)

• Jodl SJ, Worm M, Friedrichs F, Heinzel-Pleines U, Wagenfeld A, Feldmuller M, Klein S, Zhang R, Shakery K, Holzmann RD, Rohde B, Perera V. Efficacy and Safety of Zabedosertib, an Interleukin-1 Receptor-Associated Kinase 4 Inhibitor, in Patients with Moderate-to-Severe Atopic Dermatitis: A Phase II Randomized Study. Dermatol Ther (Heidelb). 2025 Nov;15(11):3329-3345. doi: 10.1007/s13555-025-01505-z. Epub 2025 Sep 4.

  PMID: 40906353 DERIVED

Related Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

zabedosertib

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2022
• First Posted: December 19, 2022
• Study Start: December 21, 2022
• Primary Completion: January 3, 2024
• Study Completion: January 31, 2024
• Last Updated: February 18, 2025
• Results First Posted: February 18, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

PL (4); CZ (3); US (4); DE (2); IT (4); GB (2); FR (3)