Study 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

Trial summary

Enrollment Goal

Trial Dates

December 2022 - January 2024

Phase

Phase 2

Could I Receive a placebo

Yes

Products

Zabedosertib (BAY1834845)

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed	Hautarztpraxis Prof. Dr. med. Christian Termeer	Stuttgart, 70499, Germany
Completed	Charité - Universitätsmedizin Berlin	Berlin, 10117, Germany
Completed	Whipps Cross University Hospital - Clinical Research Unit	Leytonstone, E11 1NR, United Kingdom
Completed	Medicines Evaluation Unit	Wythenshawe, M23 9QZ, United Kingdom
Completed	Beth Israel Deaconess Medical Center - Dermatology	Boston, 02115, United States
Completed	University of Cincinnati College of Medicine - Dermatology	Cincinnati, 45219, United States
Completed	Arlington Research Center, Inc. \| Arlington, TX	Arlington, 76011, United States
Completed	NorthShore University HealthSystem \| Skokie Hospital - Dermatology Department	Skokie, 60077, United States
Completed	Hôpital Saint Louis	PARIS, 75010, France
Completed	Centre Hospitalier Universitaire Nice \| L'Archet Hospital - Dermatology Department	NICE CEDEX 3, 6202, France
Completed	Clinique Bezannes	Bezannes, 51430, France
Completed	Dermal NZOZ Sp Osrodek Dermatologiczny Bialystok-Podlasie	Bialystok, 15-453, Poland
Completed	Centrum Nowoczesnych Terapii Dobry Lekarz	Krakow, 31-011, Poland
Completed	Royalderm Agnieszka Nawrocka	Warszawa, 02-962, Poland
Completed	Santa Sp. z o.o.	Lodz, 90-302, Poland
Completed	Humanitas Research Hospital \| Cardio Center - Clinical, Interventional Cardiology and Coronary Care	Milano, 20089, Italy
Completed	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano, 20122, Italy
Completed	Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania	Catania, 95123, Italy
Completed	University Hospital Of Ferrara	Ferrara, 44124, Italy
Completed	Dermamedica s.r.o.	Nachod, 547 01, Czech Republic
Completed	Clintrial s.r.o.	Praha 10, 100 00, Czech Republic
Completed	PRAGLANDIA	Praha 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.
Time 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.
Time 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.
Time 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.
Time 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.
Time 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.
Time 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.
Time 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.
Time 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.
Time Frame:
Baseline and Week 12 (Day 84)
Frequency and severity of treatment-emergent adverse events (TEAEs)
Time 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

Additional Information

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