Evaluation of Amlitelimab Efficacy and Safety in Moderate-to-Severe Atopic Dermatitis with Topical Corticosteroids: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to demonstrate the **efficacy** of amlitelimab in comparison to placebo in participants aged 12 years and older with moderate-to-severe atopic dermatitis (AD) on background topical therapies. This is clinically relevant as it aims to establish amlitelimab as a potential therapeutic option for managing moderate-to-severe AD, a condition that significantly impacts quality of life and often requires effective long-term management strategies.

Secondary objectives include: - Assessing the efficacy of amlitelimab compared to placebo in the same participant group, which further supports the primary objective by providing additional efficacy data. - Evaluating the **safety profile** of amlitelimab compared to placebo, which is crucial for understanding the risk-benefit ratio of the treatment. - Characterizing the **pharmacokinetic profile** of amlitelimab, which provides insights into the drug's absorption, distribution, metabolism, and excretion. - Characterizing the **immunogenicity** of amlitelimab, which is important for assessing the potential for immune responses that could affect treatment efficacy and safety.

The clinical trial involves a total of **698 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 must 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 a **Phase 3**, randomized, double-blind, placebo-controlled, parallel-group, 3-arm study designed to evaluate the efficacy and safety of **amlitelimab** administered via subcutaneous injection in participants aged 12 years and older with moderate-to-severe **atopic dermatitis** on background topical corticosteroids. The trial is multinational and multicenter, with an estimated recruitment start date of April 26, 2024, and an estimated end date of May 25, 2026. The trial involves a total duration of 24 weeks for each participant, during which they will be randomly assigned to one of the three study arms: amlitelimab, placebo, or an auxiliary treatment group.

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 therapies. Baseline assessments will include the **Eczema Area and Severity Index (EASI)** score and the **Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD)**. Following randomization, participants will attend regular follow-up visits to monitor treatment efficacy and safety, with primary endpoints assessed at Week 24. These endpoints include the proportion of participants achieving a vIGA-AD score of 0 or 1 and a reduction from baseline of at least 2 points, as well as those reaching a 75% reduction in EASI score (EASI-75).

The end-of-study visit will occur at the conclusion of the 24-week treatment period, where final assessments will be conducted to evaluate the long-term effects of the treatment. Participant involvement is expected to last for the entire 24-week period unless early termination is warranted due to adverse events, non-compliance with study procedures, or withdrawal of consent. The trial is structured to ensure rigorous monitoring and data collection to support the evaluation of amlitelimab's efficacy and safety in the target population.

The clinical trial involves the use of several treatments, including **Amlitelimab**, **Pimecrolimus**, **Tacrolimus**, and a **Placebo**. **Amlitelimab** is administered as a solution for injection in a pre-filled syringe, containing the active substance **AMLITELIMAB**, a protein classified as an OX40 ligand. The administration route is subcutaneous injection. The maximum daily dose is 250 mg, with a total maximum dose of 875 mg over a treatment period of 24 weeks. The device used for administration is a prefilled syringe with a staked needle, plunger rod, and backstop. Compliance with dosing schedules is monitored throughout the study.

**Pimecrolimus** is used as an auxiliary treatment in the trial. It is a chemical substance applied topically. The pharmaceutical form is denoted as PHF00017MIG. The maximum daily and total doses are not specified, and the treatment period is limited to one week. Participant compliance is ensured through regular monitoring and documentation of application frequency.

**Tacrolimus** is another auxiliary treatment, also applied topically. It is a chemical substance with the pharmaceutical form PHF00156MIG. Similar to **Pimecrolimus**, the maximum daily and total doses are not specified, and the treatment period is one week. Compliance is monitored through participant logs and study visits.

The **Placebo** is used as a control in the study. It does not contain any active substance and is administered in a manner consistent with the experimental treatments to maintain blinding. The placebo is used to evaluate the efficacy of **Amlitelimab** in comparison to a non-active treatment. Compliance with placebo administration is monitored similarly to the active treatments.

Additionally, participants are allowed to use background topical corticosteroids as part of the standard-of-care therapy for moderate-to-severe atopic dermatitis. The use of these non-experimental treatments is documented and monitored to ensure consistency and adherence to the study protocol.

The efficacy of amlitelimab in the treatment of moderate-to-severe **atopic dermatitis** will be assessed in a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multinational, multicenter clinical trial. The primary endpoints for evaluating efficacy 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 the EU, EU reference countries, Japan, the US, and US reference countries.

Secondary endpoints will further evaluate efficacy through various measures, including the proportion of participants achieving EASI-75, EASI-90, and EASI-100, as well as changes in Dermatology Life Quality Index (DLQI), Children Dermatology Life Quality Index (CDLQI), and Hospital Anxiety Depression Scale (HADS). Additional assessments will include changes in the weekly average of daily Peak Pruritus-Numerical Rating Scale (PP-NRS), Skin Pain-Numerical Rating Scale (SP-NRS), and Sleep Disturbance-Numerical Rating Scale (SD-NRS) from baseline. The trial will also monitor the proportion of participants with a reduction in these scales, as well as changes in the Scoring Atopic Dermatitis (SCORAD) index and Patient Oriented Eczema Measure (POEM) from baseline.

Data collection will occur at specified timepoints, with primary and secondary endpoints primarily assessed at Week 24. The trial will utilize validated scales and instruments to ensure the accuracy and reliability of the efficacy assessments. The study aims to provide comprehensive data on the efficacy of amlitelimab in improving the clinical symptoms and quality of life for participants with moderate-to-severe atopic dermatitis.