Evaluation of Amlitelimab Monotherapy in Maintaining Treatment Response in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis

The primary objective of this study is to demonstrate the maintenance of treatment response to **amlitelimab** monotherapy administered every four weeks (Q4W) compared to treatment withdrawal, and subsequently, to compare amlitelimab monotherapy administered every twelve weeks (Q12W) with treatment withdrawal in responders with moderate-to-severe **atopic dermatitis** (AD). This is clinically relevant as it aims to establish the efficacy of amlitelimab in sustaining therapeutic benefits in patients who have previously responded to treatment, potentially offering a long-term management strategy for AD.

Secondary objectives include:

• For responders from parent studies, to demonstrate the maintenance of treatment response to amlitelimab monotherapy compared to treatment withdrawal in responders with moderate-to-severe AD.
• For non-responders from parent studies, to characterize the treatment response to amlitelimab monotherapy in non-responders with moderate-to-severe AD.
• For all participants, to assess the safety profile of amlitelimab monotherapy as maintenance therapy in participants with moderate-to-severe AD.
• To assess the pharmacokinetic (PK) profile of amlitelimab monotherapy as maintenance therapy in participants with moderate-to-severe AD.
• To assess the immunogenicity of amlitelimab monotherapy as maintenance therapy in participants with moderate-to-severe AD.

The clinical trial involves a total of **982 participants** diagnosed with **atopic dermatitis**, specifically targeting those with moderate-to-severe conditions. The study population includes both male and female subjects, with an age range starting from 12 years and above. Participants were selected based on their prior involvement in one of the three 24-week parent studies, namely EFC17559 (COAST-1), EFC17560 (COAST-2), or EFC17561 (SHORE), where they received study treatment without permanent investigational medicinal product discontinuation. The trial includes individuals who are able and willing to comply with study visits and procedures, and who have a body weight of at least 25 kg. The study population is characterized by a diverse age range and includes a vulnerable population, ensuring a comprehensive assessment of the treatment's efficacy across different demographic groups.

The clinical trial is a **randomized**, **double-blind**, placebo-controlled study designed to evaluate the treatment response and safety of two dose regimens of **amlitelimab** administered as monotherapy by subcutaneous injection in participants aged 12 years and older with moderate-to-severe **atopic dermatitis**. The trial is structured as a 52-week extension study, following participants who have previously completed one of the three 24-week parent studies. The primary objective is to demonstrate the maintenance of treatment response to amlitelimab compared to treatment withdrawal. The trial will include a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, prior participation in parent studies, and body weight. Participants will then undergo regular follow-up visits to monitor treatment response and safety, with the primary endpoint being the proportion of participants maintaining treatment response at Week 48. The end-of-study visit will conclude the trial, assessing the overall efficacy and safety of the treatment. Participant involvement is expected to last for the entire 52-week duration unless conditions such as adverse events or withdrawal of consent necessitate early termination. The trial is designed to ensure rigorous assessment of the investigational product's efficacy and safety, with the use of a placebo control to provide a robust comparison. The study's methodology and design adhere to high standards of clinical research, ensuring the reliability and validity of the findings.

The clinical trial involves the administration of **Amlitelimab**, an experimental medication, which is a **solution for injection in a pre-filled syringe**. Amlitelimab is a **human IgG4 monoclonal antibody against OX40 Ligand**. It is administered via **subcutaneous injection**. The trial includes two dosing regimens: a maximum daily dose of 250 mg with a total dose of 500 mg, and a second regimen with a maximum daily dose of 125 mg and a total dose of 250 mg. The treatment period extends up to 52 weeks. The pre-filled syringe device includes a staked needle, plunger rod, and backstop (finger flange) for ease of administration. Participant compliance is monitored throughout the study to ensure adherence to the dosing schedule.

In addition to the experimental treatment, the study includes a **placebo** group. The placebo is not specified in terms of pharmaceutical form or active substance, and it serves as a control to evaluate the efficacy of Amlitelimab. The placebo is administered in a manner consistent with the experimental treatment to maintain the double-blind nature of the trial.

Non-experimental treatments used in the study include **Pimecrolimus** and **Tacrolimus**, both of which are administered topically. These treatments are classified as auxiliary medications and are used for a maximum treatment period of 1 week. Pimecrolimus and Tacrolimus are chemical substances, with Pimecrolimus being identified by the ATC code D11AH02 and Tacrolimus by D11AH01. These treatments are included to provide standard-of-care therapy for participants as needed.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints designed to evaluate the treatment response in participants with moderate-to-severe **atopic dermatitis**. The primary endpoint is the proportion of participants who maintain treatment response at Week 48 of the study. Secondary endpoints include various measures of clinical improvement, such as the proportion of participants who continue to achieve EASI-75, EASI-50, EASI-90, and EASI-100 scores, as well as those who maintain a vIGA-AD score of 0 (clear) or 1 (almost clear). Additional secondary endpoints involve the assessment of changes in the Eczema Area and Severity Index (EASI), the Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD), and the Pruritus Numerical Rating Scale (PP-NRS), among others.

These efficacy parameters will be measured at specific timepoints throughout the 52-week extension study. The trial will utilize validated scales and instruments to ensure accurate and reliable data collection. The analysis will focus on both responders and non-responders from the parent studies, with particular attention to the maintenance of treatment response and the time to the first event of loss of response. The study will also monitor the incidence of treatment-emergent adverse events and the presence of antidrug antibodies to amlitelimab. The data collected will provide comprehensive insights into the efficacy of amlitelimab as a monotherapy administered via subcutaneous injection.