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 (Damask)

• ClinicalTrials.gov Identifier: NCT05656911
• Recruitment Status: Completed
• First Posted: December 19, 2022
• Last Update Posted: February 28, 2024
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: November 29, 2022
• First Posted Date: December 19, 2022
• Last Update Posted Date: February 28, 2024
• Actual Study Start Date: December 21, 2022
• Actual Primary Completion Date: January 3, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 16, 2022)

Number of participants having achievement of 75% reduction from baseline in the Eczema Area and Severity Index (EASI 75 response) at Week 12 (Day 84) [ Time Frame: Baseline and up to Week 12 (Day 84) ]

The endpoint is 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 EASI is a ClinRO assessing the extent of AD at four body regions (head and neck, trunk and upper and lower extremities) by measuring the average severity of four clinical signs at each body region: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale of 0 to 3 (Hanifin et al, 2001). The minimum EASI score is 0 and the maximum EASI score is 72, with a higher score indicating worse severity of AD.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 16, 2022)

• Percent change from baseline in EASI at Week 12 (Day 84) [ Time Frame: Baseline and up to Week 12 (Day 84) ]
  EASI stands for Eczema Area and Severity Index. The EASI is a ClinRO assessing the extent of atopic dermatitis (AD) at four body regions (head and neck, trunk and upper and lower extremities) by measuring the average severity of four clinical signs at each body region: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale of 0 to 3 (Hanifin et al, 2001). The minimum EASI score is 0 and the maximum EASI score is 72, with a higher score indicating worse severity of AD.
• Number of participants having achievement of EASI 50 response at Week 12 (Day 84) [ Time Frame: up to Week 12 (Day 84) ]
  EASI stands for Eczema Area and Severity Index. The EASI is a ClinRO assessing the extent of atopic dermatitis (AD) at four body regions (head and neck, trunk and upper and lower extremities) by measuring the average severity of four clinical signs at each body region: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale of 0 to 3 (Hanifin et al, 2001). The minimum EASI score is 0 and the maximum EASI score is 72, with a higher score indicating worse severity of AD.
• Number of participants having achievement of EASI 90 response at Week 12 (Day 84) [ Time Frame: up to Week 12 (Day 84) ]
  EASI stands for Eczema Area and Severity Index. The EASI is a ClinRO assessing the extent of atopic dermatitis (AD) at four body regions (head and neck, trunk and upper and lower extremities) by measuring the average severity of four clinical signs at each body region: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale of 0 to 3 (Hanifin et al, 2001). The minimum EASI score is 0 and the maximum EASI score is 72, with a higher score indicating worse severity of AD.
• Number of participants having achievement of a vIGA-AD response (score 0 or 1 and ≥ 2 points improvement) at Week 12 (Day 84) [ Time Frame: up to 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.
• Absolute change from baseline in body surface area (BSA) affected by atopic dermatitis (AD) at Week 12 (Day 84) [ Time Frame: up to 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 [ Time Frame: Baseline and up to Week 12 (Day 84) ]
  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.
• Absolute values of weekly average of the Peak Pruritus 0-10 numerical rating scale (NRS) score from baseline at Week 12 (Day 84) [ Time Frame: Baseline and up to 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.
• Percent change of weekly average of the Peak Pruritus 0-10 NRS score from baseline at Week 12 (Day 84) [ Time Frame: Baseline and up to Week 12 (Day 84) ]
  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.
• Frequency and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: After the first treatment with the study intervention and until 7 days after the last intake of study intervention (approximately up to 91 days) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Atopic Dermatitis

Intervention

• Drug: Zabedosertib (BAY1834845)
  Oral administration, two times a day
• Drug: Placebo to zabedosertib (BAY 1834845)
  Oral administration, two times a day

Study Arms

• Experimental: Zabedosertib
  Participants will receive zabedosertib for up to 12 weeks (84 days).
  Intervention: Drug: Zabedosertib (BAY1834845)
• Placebo Comparator: Matching placebo to zabedosertib
  Participants will receive placebo to zabedosertib for up to 12 weeks (84 days).
  Intervention: Drug: Placebo to zabedosertib (BAY 1834845)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 26, 2024): 77
• Original Estimated Enrollment (submitted: December 16, 2022): 72
• Actual Study Completion Date: January 31, 2024
• Actual Primary Completion Date: January 3, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czechia, France, Germany, Italy, Poland, United Kingdom, United States

Administrative Information

• NCT Number: NCT05656911
• Other Study ID Numbers: 22158; 2022-000520-38 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

• Current Responsible Party: Bayer
• Original Responsible Party: Same as current
• Current Study Sponsor: Bayer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Bayer
• Verification Date: February 2024