Efficacy and Safety Evaluation of Subcutaneous Amlitelimab in Moderate-to-Severe Atopic Dermatitis with Background Topical Corticosteroids in Adolescents and Adults

The primary objective of this study is to demonstrate the **efficacy** of amlitelimab administered by subcutaneous injection in comparison to placebo in participants aged 12 years and older with moderate to severe **atopic dermatitis** (AD). This is clinically relevant as it aims to provide an alternative treatment option for patients who have had an inadequate response to prior biologic or oral Janus Kinase (JAK) inhibitor therapy, potentially improving patient outcomes and quality of life.

Secondary objectives include:

• Assessing the effects of amlitelimab on signs, symptoms, quality of life, and mental health in the target population.
• Evaluating the safety profile of amlitelimab compared to placebo.
• Characterizing the pharmacokinetic profile of amlitelimab.
• Characterizing the immunogenicity of amlitelimab.

The clinical trial involves a total of **196 participants** diagnosed with **atopic dermatitis**. The study population includes both male and female subjects aged 12 years and older, with a specific focus on individuals who have moderate to severe forms of the condition. Participants are required to have a documented history of inadequate response to prior biologic or oral JAK inhibitor therapy, and they must be on background topical therapies. The trial population was selected based on specific inclusion criteria, such as a diagnosis of atopic dermatitis for at least one year, a v-IGA-AD score of 3 or 4, an EASI score of 16 or higher, and at least 10% body surface area involvement. Additionally, participants must have a body weight of at least 25 kg and a weekly average of daily PP-NRS of 4 or higher at baseline. The study considers lifestyle factors such as the ability and willingness to comply with study visits and procedures. Both vulnerable and non-vulnerable populations are included in the trial, ensuring a comprehensive evaluation of the treatment's efficacy across diverse demographic groups.

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** administered by subcutaneous injection in participants aged 12 years and older with moderate-to-severe **atopic dermatitis**. The trial will include participants who are on background topical corticosteroids and have had an inadequate response to prior biologic therapy or oral Janus Kinase (JAK) inhibitor treatment. The study is multinational and multicenter, with an estimated recruitment start date of May 28, 2024, and an estimated end date of October 30, 2026, making the overall trial duration approximately 29 months.

Participants will undergo a sequence 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 previous treatments. Following successful screening, participants will be randomized into one of the study arms. The trial includes multiple follow-up visits to monitor efficacy and safety outcomes, with primary endpoints assessed at Week 36. These endpoints include 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 at least 2 points, as well as a 75% reduction from baseline in the Eczema Area and Severity Index (EASI) score. Secondary endpoints will also be evaluated throughout the study duration.

The expected length of participant involvement is up to 36 weeks, with conditions for early termination including non-compliance with study procedures, adverse events, or withdrawal of consent. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to ensure participant safety and collect final data for analysis. The trial aims to provide comprehensive data on the efficacy and safety of amlitelimab in the specified patient population, contributing valuable insights into the management of moderate-to-severe atopic dermatitis.

The clinical trial involves the administration of **Amlitelimab**, a solution for injection in a pre-filled syringe. Amlitelimab is a monoclonal antibody targeting the OX40 ligand, developed by Sanofi Aventis Recherche et Développement (SAR). It is administered via **subcutaneous injection**. The maximum daily dose is 500 mg, with a total maximum dose of 2500 mg over a treatment period of up to 36 weeks. The pre-filled syringe is classified as a medicinal product combined with an integral medical device, serving solely as a delivery system for the medicinal product. The device itself is not under investigation in this trial.

Participants will also receive a **Placebo** as part of the study design. The placebo is used to maintain the double-blind nature of the trial and is administered in a manner consistent with the experimental treatment, although specific details regarding its pharmaceutical form and route of administration are not provided.

In addition to the experimental treatment, participants will continue using background topical therapies, including **Tacrolimus** and **Pimecrolimus**. Tacrolimus is a topical immunosuppressant with the active substance name Tacrolimus Anhydrous, classified under the ATC code D11AH01. Pimecrolimus, also a topical immunosuppressant, is classified under the ATC code D11AH02. Both are applied topically, and their dosage forms are not specified in terms of daily or total dose amounts, as they are used as background therapies in conjunction with the primary investigational product.

Throughout the trial, participant compliance with the dosing schedule will be monitored to ensure adherence to the treatment regimen. The trial aims to evaluate the efficacy and safety of Amlitelimab in participants with moderate-to-severe atopic dermatitis who have had an inadequate response to prior biologic therapy or oral Janus Kinase (JAK) inhibitor treatment.

The efficacy of the investigational product, **amlitelimab**, will be assessed in a Phase 3, randomized, double-blind, placebo-controlled, parallel-group clinical trial involving participants aged 12 years and older with moderate-to-severe atopic dermatitis. 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 36, and the proportion of participants reaching a 75% reduction from baseline in the Eczema Area and Severity Index (EASI 75) score at Week 36.

Secondary endpoints will further assess 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) and Children Dermatology Life Quality Index (CDLQI) scores. Additional assessments will include changes in the Hospital Anxiety Depression Scale (HADS), Skin Pain-Numerical Rating Scale (SP-NRS), Sleep Disturbance-Numerical Rating Scale (SD-NRS), and Scoring Atopic Dermatitis (SCORAD) index. The trial will also evaluate the proportion of participants with a reduction in Patient Oriented Eczema Measure (POEM) scores and the incidence of antidrug antibodies (ADAs) of amlitelimab.

These efficacy parameters will be measured at various timepoints, including baseline and Week 36, using validated scales and patient-reported outcomes. The data collected will be analyzed to determine the efficacy of amlitelimab in comparison to placebo, with the aim of demonstrating significant improvements in the clinical manifestations of atopic dermatitis.