A phase 2b, randomised, double-blind, placebo-controlled, multi-site, parallel-group, dose finding trial to evaluate the efficacy and safety of different doses of subcutaneously administered LEO 138559 in adult subjects with moderate-to-severe atopic dermatitis (AD)

Trial ID: 2022-500777-14-00
Protocol: LP0145-2240
Sponsor: Leo Pharma A/S

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Diseases & Conditions

Dermatitis atopic

Objectives

The primary objective of this study is to compare the **efficacy** of four different dosage regimens of LEO 138559 with placebo in subjects with moderate-to-severe **Atopic Dermatitis** (AD). This is clinically relevant as it aims to determine the optimal dosing strategy for LEO 138559, potentially improving therapeutic outcomes for patients suffering from this chronic inflammatory skin condition.

Secondary objectives include:

Comparing the **safety** of four different dosage regimens of LEO 138559 with placebo in the same patient population. This will provide insights into the risk profile associated with each dosing regimen, ensuring that the treatment is not only effective but also safe for long-term use.

Participants

The clinical trial involves a total of **97 participants** diagnosed with **Atopic Dermatitis**. The study population comprises both male and female subjects, aged between **18 and 75 years**. Participants were selected based on a confirmed diagnosis of moderate-to-severe atopic dermatitis, as defined by the Hanifin and Rajka criteria, with a history of the condition for at least one year. The trial excludes vulnerable populations. Participants have a documented inadequate response to treatment with topical corticosteroids, with or without topical calcineurin inhibitors, or have been advised against these treatments due to significant side effects or safety concerns. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that participants have an Eczema Area and Severity Index (EASI) score of at least 12 at screening and 16 at baseline, a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 3 or higher, a body surface area (BSA) involvement of at least 10%, and an Atopic Dermatitis Symptom Diary (ADSD) Worst Itch score of 4 or higher at baseline.

Plans and Procedures

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled**, multi-site, parallel-group, dose-finding study designed to evaluate the efficacy and safety of different doses of LEO 138559 in adult subjects with moderate-to-severe **atopic dermatitis**. The trial aims to compare four different dosage regimens of LEO 138559, a **humanised IgG1 monoclonal antibody against interleukin 22 receptor subunit alpha**, with a placebo. The study is expected to last for approximately 16 weeks, with participant involvement beginning from the screening visit and concluding at the end-of-study visit.

Participants will undergo a series of study visits, starting with the inclusion (screening) visit, where eligibility will be assessed based on criteria such as age (18-75 years), a confirmed diagnosis of atopic dermatitis, and a history of inadequate response to topical corticosteroids. Baseline assessments will include the Eczema Area and Severity Index (EASI) score, vIGA-AD score, and Body Surface Area (BSA) of atopic dermatitis involvement. Following the screening, eligible participants will be randomized to receive either LEO 138559 or placebo via subcutaneous injection.

Throughout the trial, participants will attend regular follow-up visits to monitor treatment efficacy and safety. The primary endpoint is the percent change in EASI score from baseline to Week 16, while secondary endpoints include the number of treatment-emergent adverse events (TEAEs) recorded for each subject. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to evaluate the overall outcomes of the treatment.

Participants are expected to remain in the study for the full duration unless specific conditions necessitate early termination, such as significant adverse events or withdrawal of consent. The trial is structured to ensure rigorous assessment of the investigational product's efficacy and safety, contributing valuable data to the understanding of treatment options for moderate-to-severe atopic dermatitis.

Treatment

The clinical trial involves the administration of **LEO138559**, a **solution for injection** with a concentration of 150 mg/ml. This investigational product is a **humanised IgG1 monoclonal antibody** targeting the **interleukin 22 receptor subunit alpha**. The pharmaceutical form is a solution intended for **subcutaneous use**. The trial is designed to evaluate the efficacy and safety of different dosage regimens of LEO138559 in adult subjects with moderate-to-severe atopic dermatitis. The maximum treatment period for this investigational product is 16 weeks. The dosing schedule and specific dosage regimens are determined as part of the trial protocol, with compliance monitored through standard clinical trial procedures.

The study also includes a **placebo** as a comparator treatment. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is administered in a manner consistent with the investigational product to ensure blinding is maintained. The placebo does not contain any active pharmaceutical ingredients and serves as a control to assess the efficacy of LEO138559. Compliance with the administration of the placebo is monitored similarly to the investigational product, ensuring adherence to the trial protocol.

Efficacy

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the percent change in the Eczema Area and Severity Index (EASI) score from baseline to Week 16. This endpoint will provide a quantitative measure of the improvement in **atopic dermatitis** severity in response to the treatment. The EASI score is a validated tool commonly used in clinical trials to assess the extent and severity of eczema. Secondary endpoints include the number of treatment-emergent adverse events (TEAEs) recorded for each subject from baseline to Week 16, which will help evaluate the safety profile of the treatment. Data collection will occur at specified timepoints, with assessments conducted at baseline and at Week 16. The trial is designed as a phase 2b, randomized, double-blind, placebo-controlled, multi-site, parallel-group study to compare the efficacy of four different dosage regimens of LEO 138559 with placebo in adult subjects with moderate-to-severe atopic dermatitis.

Inclusion and Exclusion Criteria

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Inclusion Criteria

18-75 years old (both included) at screening (Visit 1).
At screening, diagnosis of - AD as defined by the Hanifin and Rajka (1980) criteria for AD. History of AD for ≥1 year.
Subjects who have a recent history (within 12 months before screening) with documented inadequate response to treatment with TCS (±TCI as appropriate) or for whom these topical AD treatments are medically inadvisable (e.g. due to important side effects or safety risks).
EASI score ≥12 at screening and ≥16 at baseline.
vIGA-AD score ≥3 at screening and baseline.
BSA of AD involvement ≥10% at screening and baseline.
ADSD Worst Itch score (weekly average) ≥4 at baseline.

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Exclusion Criteria

History of clinically significant infection within 4 weeks prior to baseline which, in the opinion of the investigator, may compromise the safety of the subject in the trial, interfere with evaluation of the IMP, or reduce the subject’s ability to participate in the trial. Clinically significant infections are defined as: - a systemic infection. - a serious skin infection requiring parenteral (IV or intramuscular) antibiotics, antiviral, or antifungal medication.
Non-serious skin infection within 7 days prior to baseline.
Presence of hepatitis B or C infection at screening.
History of HIV infection or positive HIV serology at screening.
Evidence of active or latent tuberculosis according to local standard of care for patients requiring initiation of a biologic treatment.
Women who are pregnant or breastfeeding.
Previous exposure to fezakinumab (anti-IL-22 Ab).
Systemic treatment with immunosuppressive drugs (e.g. methotrexate, cyclosporine, azathioprine), immunomodulating drugs, retinoids (e.g. alitretinoin), corticosteroids (steroid eyedrops and inhaled or intranasal steroids are allowed), or JAK inhibitors within 28 days or 5 half-lives prior to baseline, whichever is longer.
Use of tanning beds or phototherapy (NBUVB, UVB, UVA1, PUVA), within 4 weeks prior to baseline.
Receipt of blood products within 28 days prior to screening.
Treatment with: - Any marketed or investigational biologic agents within 3 months or 5 half-lives, whichever is longer, prior to baseline. - Any cell-depleting agents including but not limited to rituximab: within 6 months prior to baseline, or until lymphocyte count returns to normal, whichever is longer.
Treatment with TCS, TCI, topical PDE-4 inhibitors, topical JAK inhibitors, or other medicated topical treatments within 7 days prior to baseline
Receipt of live attenuated vaccines 30 days prior to baseline.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Czechia	Not Recruiting	30 Oct 2023	20
France	Not Recruiting	30 Oct 2023	16
Germany	Not Recruiting	30 Oct 2023	30
Hungary	Not Recruiting	30 Oct 2023	13
Poland	Not Recruiting	30 Oct 2023	36
Romania	Not Recruiting	30 Oct 2023	20
Spain	Not Recruiting	30 Oct 2023	18