A Phase 3, randomized, double-blind, placebo-controlled, parallel-group, 3-arm, multinational, multicenter study to evaluate the efficacy and safety of amlitelimab monotherapy by subcutaneous injection in participants aged 12 years and older with moderate-to-severe atopic dermatitis - EFC17559 / COAST1

The primary objective of this study is to demonstrate the **efficacy** of amlitelimab monotherapy compared to placebo in participants aged 12 years and older with moderate-to-severe atopic dermatitis (AD). This is clinically relevant as it aims to establish amlitelimab as a potential therapeutic option for managing AD, a chronic inflammatory skin condition that significantly impacts quality of life.

Secondary objectives include:

• Assessing the efficacy of amlitelimab monotherapy in comparison to placebo in the same participant group.
• Evaluating the **safety profile** of amlitelimab monotherapy.
• Characterizing the **pharmacokinetic profile** of amlitelimab monotherapy.
• Characterizing the **immunogenicity** of amlitelimab monotherapy.

The clinical trial involves a total of **592 participants** diagnosed with **atopic dermatitis**. The study population includes both male and female subjects aged 12 years and older, with a focus on individuals experiencing moderate-to-severe forms of the condition. Participants were selected based on specific criteria, including a documented history of inadequate response to topical or systemic therapies and a diagnosis of atopic dermatitis for at least one year. The trial population is characterized by a **vulnerable population** designation, indicating the inclusion of individuals who may require additional considerations. Participants are required to have a body weight of at least 25 kg and demonstrate a willingness to comply with study visits and procedures. The trial does not specify particular lifestyle considerations such as diet or physical activity. The sponsor has not provided additional information regarding the general health status or specific lifestyle habits of the participants.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, parallel-group, 3-arm study to evaluate the efficacy and safety of **amlitelimab** monotherapy administered via **subcutaneous injection** in participants aged 12 years and older with moderate-to-severe **atopic dermatitis**. The trial is multinational and multicenter, with an estimated recruitment start date of May 13, 2024, and an estimated end date of November 14, 2025. The trial's primary objective is to demonstrate the efficacy of amlitelimab compared to placebo, with primary endpoints including the proportion of participants achieving a Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) of 0 or 1 and a reduction from baseline of ≥2 points at Week 24, as well as the proportion of participants reaching a 75% reduction from baseline in the Eczema Area and Severity Index (EASI-75) score at Week 24.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, diagnosis of atopic dermatitis for at least one year, and documented history of inadequate response to topical or systemic treatments. Following randomization, participants will receive either amlitelimab or placebo, with follow-up visits scheduled to monitor efficacy and safety outcomes. The end-of-study visit will occur at the conclusion of the 24-week treatment period. The expected length of participant involvement is approximately 24 weeks, with conditions for early termination including non-compliance with study procedures or the occurrence of adverse events that necessitate withdrawal for safety reasons.

The clinical trial involves the administration of **Amlitelimab**, a **human IgG4 monoclonal antibody against OX40 ligand**, as the primary experimental medication. Amlitelimab is provided in the form of a **solution for injection in a pre-filled syringe**. The medication is administered via **subcutaneous injection**. The dosing regimen includes a maximum daily dose of 250 mg, with a total maximum dose of 875 mg over a treatment period of 24 weeks. Amlitelimab is also available in a higher dosage form, with a maximum daily dose of 500 mg and a total maximum dose of 1750 mg over the same treatment period. The pre-filled syringe device includes a staked needle, plunger rod, and backstop (finger flange) for ease of administration. Participant compliance with the dosing schedule is monitored throughout the study.

In addition to the experimental treatment, the study includes a **placebo** group to serve as a comparator. The placebo is administered in a manner consistent with the experimental treatment to maintain the double-blind nature of the trial. The placebo does not contain any active pharmaceutical ingredients and is used to evaluate the efficacy and safety of Amlitelimab by comparison.

Non-experimental treatments in the study include **Pimecrolimus** and **Tacrolimus**, both of which are administered topically. Pimecrolimus is a chemical substance with an ATC code of D11AH02, and Tacrolimus is classified under ATC code D11AH01. These treatments are used as auxiliary medications and are not the primary focus of the trial. The maximum treatment period for these topical agents is 1 week, and they are included to provide additional context for the study's findings.

Another auxiliary treatment category in the study is **Corticosteroids, Plain**, classified under ATC code D07A. This category includes various corticosteroid formulations used topically. The specific active substances within this category are not specified due to the diversity of the ATC level selected. The inclusion of this treatment category aims to provide a comprehensive understanding of the therapeutic landscape for moderate-to-severe atopic dermatitis.

The efficacy of **amlitelimab** monotherapy in the treatment of moderate-to-severe atopic dermatitis will be assessed through a series of primary and secondary endpoints. The primary endpoints include the proportion of participants achieving a Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) score of 0 (clear) or 1 (almost clear) with a reduction from baseline of at least 2 points at Week 24, and the proportion of participants reaching a 75% reduction from baseline in the Eczema Area and Severity Index (EASI-75) score at Week 24. These assessments will be conducted in both EU and US reference countries.

Secondary endpoints will further evaluate the efficacy by measuring additional parameters such as the proportion of participants achieving EASI-75, EASI-90, and EASI-100, as well as changes in the Dermatology Life Quality Index (DLQI) and Children Dermatology Life Quality Index (CDLQI). Other secondary measures include changes in the Hospital Anxiety Depression Scale (HADS), the Patient Oriented Eczema Measure (POEM), and the Scoring Atopic Dermatitis (SCORAD) index. The study will also assess the proportion of participants with a reduction in the weekly average of daily Peak Pruritus-Numerical Rating Scale (PP-NRS) and Sleep Disturbance-Numerical Rating Scale (SD-NRS) from baseline. These efficacy parameters will be collected and analyzed at specified timepoints, including Week 24, using validated scales and patient-reported outcomes.