A Study to Evaluate the Efficacy and Safety of Subcutaneous Amlitelimab Monotherapy Compared With Placebo in Participants Aged 18 Years and Older With Moderate-to-severe Atopic Dermatitis (COAST 2)

Study Overview
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Brief Summary
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This is a parallel group, Phase 3, multinational, multicenter, randomized, double blind, placebo-controlled, 3-arm monotherapy study for treatment of participants diagnosed with moderate to severe atopic dermatitis (AD), whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. The purpose of this study is to measure the efficacy and safety of treatment with amlitelimab solution for SC injection compared with placebo in participants with moderate to severe AD aged 18 years and older. Study details include: At the end of the treatment period, participants will have an option to enter a separate study: the blinded extension study EFC17600 (ESTUARY). For participants not entering the blinded extension Study EFC17600 (ESTUARY), the study duration will be up to 44 weeks including a 2 to 4-week screening, a 24-week randomized double-blind period, and a 16-week safety follow-up. For participants entering the blinded extension Study EFC17600 (ESTUARY), the study duration will be up to 28 weeks including a 2 to 4-week screening and a 24-week randomized double-blind period. The total treatment duration will be up to 24 weeks. The total number of visits will be up to 10 visits (or 9 visits for those entering the blinded extension study EFC17600 (ESTUARY).

Official Title
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A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallelgroup, 3-arm, Multinational, Multicenter Study to Evaluate the Efficacy and Safety of Amlitelimab Monotherapy by Subcutaneous Injection in Participants Aged 18 Years and Older With Moderate-to-severe Atopic Dermatitis

Conditions
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Dermatitis Atopic

Intervention / Treatment
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* Drug: Amlitelimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be 18 years of age (when signing informed consent form) Diagnosis of AD for at least 1 year (defined by the American Academy of Dermatology Consensus Criteria) Documented history (within 6 months before screening) of either inadequate response or inadvisability to topical treatments, and/or inadequate response to systemic therapies (within 12 months before screening) v-IGA-AD of 3 or 4 at baseline visit EASI score of 16 or higher at baseline AD involvement of 10% or more of BSA at baseline Weekly average of daily PP-NRS of ≥ 4 at baseline visit. Able and willing to comply with requested study visits and procedures Body weight ≥40 kg Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Skin co-morbidity that would adversely affect the ability to undertake AD assessments Known history of or suspected significant current immunosuppression Any malignancies or history of malignancies prior to baseline (excluding for non-melanoma skin cancer excised and cured >5 years prior to baseline) History of solid organ or stem cell transplant Any active or chronic infection including helminthic infection requiring systemic treatment within 4 weeks prior baseline Positive for human immunodeficiency virus (HIV), Hepatitis B or hepatitis C at screening visit Having active tuberculosis (TB), latent TB, a history of incompletely treated TB, suspected extrapulmonary TB infection, or who are at high risk of contracting TB Having received any of the specified therapy within the specified timeframe(s) prior to the baseline visit In the Investigator's opinion, any clinically significant laboratory results or protocol specified laboratory abnormalities at screening History of hypersensitivity or allergy to any of the excipients or investigational medicinal product (IMP) The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amlitelimab dose 1<br>Subcutaneous injection as per protocol | Drug: Amlitelimab<br>* Pharmaceutical form:Injection solution-Route of administration:SC injection<br>* Other names: SAR445229;|
| Experimental: Amlitelimab dose 2<br>Subcutaneous injection as per protocol | Drug: Amlitelimab<br>* Pharmaceutical form:Injection solution-Route of administration:SC injection<br>* Other names: SAR445229;|
| Placebo Comparator: Placebo<br>Subcutaneous injection as per protocol | Drug: Placebo<br>* Pharmaceutical form:Injection solution-Route of administration:SC injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EU, EU reference countries, and Japan: Proportion of participants with Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) of 0 (clear) or 1 (almost clear) and a reduction from baseline of ≥2 points at Week 24 | The vIGA-AD is an Investigator-completed assessment scale used to determine severity of AD and clinical response to treatment. It is based on a 5-point scale, ranging from 0 (clear) to 4 (severe). | Week 24 | 
| EU, EU reference countries, and Japan: Proportion of participants reaching 75% reduction from baseline in Eczema Area and Severity Index (EASI) score (EASI-75) at Week 24 | The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD. Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD. | Week 24 | 
| US and US reference countries: Proportion of participants with vIGA-AD of 0 (clear) or 1 (almost clear) and a reduction from baseline of ≥2 points at Week 24 | The vIGA-AD is an Investigator-completed assessment scale used to determine severity of AD and clinical response to treatment. It is based on a 5-point scale, ranging from 0 (clear) to 4 (severe). | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants reaching EASI-75 at Week 24 (for US and US reference countries only) | The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD. Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD. EASI-75 is 75% reduction from baseline in EASI score. | Week 24 | 
| Proportion of participants with vIGA-AD 0 (clear) or 1 (almost clear) with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting) | The vIGA-AD is an Investigator-completed assessment scale used to determine severity of AD and clinical response to treatment. It is based on a 5-point scale, ranging from 0 (clear) to 4 (severe). | Baseline to Week 24 | 
| Proportion of participants with ≥4-point reduction in weekly average of daily Peak Pruritus-Numerical Rating Scale (PP-NRS) from baseline in participants with baseline weekly average of daily PP-NRS ≥4 | The PP-NRS is a validated single item 0-10 numeric rating scale assessing peak pruritus (itch) associated with AD with 0 = no itch and 10 = worst itch imaginable. | Baseline to Week 24 | 
| Proportion of participants reaching EASI-75 | The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD. Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD. EASI-75 is 75% reduction from baseline in EASI score. | Baseline to Week 20 | 
| Proportion of participants with vIGA-AD of 0 (clear) or 1 (almost clear) and a reduction from baseline of ≥2 points | The vIGA-AD is an Investigator-completed assessment scale used to determine severity of AD and clinical response to treatment. It is based on a 5-point scale, ranging from 0 (clear) to 4 (severe). | Baseline to Week 20 | 
| Proportion of participants reaching EASI-90 | The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD. Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD. EASI-90 is 90% reduction from baseline in EASI score. | Baseline to Week 24 | 
| Proportion of participants reaching EASI-100 | The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD. Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD. EASI-100 is 100% reduction from baseline in EASI score. | Baseline to Week 24 | 
| Change in Dermatology Quality of Life Index (DLQI) from baseline | The DLQI is a validated 10-item questionnaire to measure dermatology-specific quality of life (QoL) in adult patients. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL. | Baseline to Week 24 | 
| Proportion of participants with a reduction in DLQI ≥4 from baseline in participants with DLQI baseline ≥4 | The DLQI is a validated 10-item questionnaire to measure dermatology-specific quality of life (QoL) in adult patients. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL. | Baseline to Week 24 | 
| Change in Hospital Anxiety Depression Scale (HADS) from baseline | The HADS is 14-item questionnaire with two subscales: anxiety & depression. Each subscale (anxiety & depression) ranges 0-21. The total HADS score ranges 0-42 with higher score indicating a poorer state. | Baseline to Week 24 | 
| Proportion of participants with HADS subscale Anxiety (HADS-A) <8 in participants with baseline HADS-A ≥8 | HADS-A score ranges 0-21 with higher score indicating a poorer state. | Baseline to Week 24 | 
| Proportion of participants with HADS subscale Depression (HADS-D) <8 in participants with HADS-D baseline ≥8 | HADS-D score ranges 0-21 with higher score indicating a poorer state. | Baseline to Week 24 | 
| Change in weekly average of daily Skin Pain-Numerical Rating Scale (SP-NRS) from baseline | The SP-NRS is a single item 0-10 numeric rating scale assessing skin pain associated with AD with 0 = no pain and 10 = worst possible pain imaginable. | Baseline to Week 24 | 
| Proportion of participants with a reduction in weekly average of daily SP-NRS ≥4 from baseline in participants with baseline weekly average of daily SP-NRS ≥4 | The SP-NRS is a single item 0-10 numeric rating scale assessing skin pain associated with AD with 0 = no pain and 10 = worst possible pain imaginable. | Baseline to Week 24 | 
| Change in weekly average of daily Sleep Disturbance-Numerical Rating Scale (SD-NRS) from baseline | The SD-NRS is a single item 0-10 numeric rating scale assessing sleep disturbance associated with AD with 0 = no sleep loss and 10 = did not sleep at all. | Baseline to Week 24 | 
| Proportion of participants with a reduction in weekly average of daily SD-NRS ≥3 from baseline in participants with Baseline weekly average of daily SD-NRS ≥3 | The SD-NRS is a single item 0-10 numeric rating scale assessing sleep disturbance associated with AD with 0 = no sleep loss and 10 = did not sleep at all. | Baseline to Week 24 | 
| Proportion of participants with a reduction in weekly average of daily SD-NRS ≥5 from baseline in participants with baseline weekly average of daily SD-NRS ≥5 | The SD-NRS is a single item 0-10 numeric rating scale assessing sleep disturbance associated with AD with 0 = no sleep loss and 10 = did not sleep at all. | Baseline to Week 24 | 
| Percent change in EASI score from baseline | The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD. Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD. | Baseline to Week 24 | 
| Percent change in weekly average of daily PP-NRS from baseline | The PP-NRS is a validated single item 0-10 numeric rating scale assessing peak pruritus (itch) associated with AD with 0 = no itch and 10 = worst itch imaginable. | Baseline to Week 24 | 
| Proportion of participants reaching EASI-50 | The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD. Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD. EASI-50 is 50% reduction from baseline in EASI score. | Baseline to Week 24 | 
| Proportion of participants with EASI ≤7 | The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD. Total score ranges from 0 to 72 with a higher score indicating increased extent and severity of AD. | Baseline to Week 24 | 
| Change in percent Body Surface Area (BSA) affected by AD from baseline |  | Baseline to Week 24 | 
| Percent change in Scoring Atopic Dermatitis (SCORAD) index from baseline | The SCORAD index is a clinical tool to evaluate the extent and severity of AD. Total score ranges from 0 (absent disease) to 103 (severe disease). | Baseline to Week 24 | 
| Proportion of participants with a reduction in SCORAD ≥ 8.7 points from baseline in participants with baseline SCORAD score ≥ 8.7 | The SCORAD index is a clinical tool to evaluate the extent and severity of AD. Total score ranges from 0 (absent disease) to 103 (severe disease). | Baseline to Week 24 | 
| Proportion of participants with a reduction in Patient Oriented Eczema Measure (POEM) ≥4 from baseline in participants with POEM Baseline ≥4 | The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms on a 5-point scale; 0 (no days) to 4 (every day in the last week). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (very severe). Higher scores indicated more severe disease and poor quality of life. | Baseline to Week 24 | 
| Change in POEM from baseline | The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms on a 5-point scale; 0 (no days) to 4 (every day in the last week). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (very severe). Higher scores indicated more severe disease and poor quality of life. | Baseline to Week 24 | 
| Proportion of participants with rescue medication use [from baseline to Week 24] |  | Baseline to Week 24 | 
| Percentage of participants who experienced Treatment-Emergent Adverse Events (TEAEs), experienced Treatment-Emergent Serious Adverse Events (TESAEs) and/or Treatment-Emergent Adverse Events of Special Interest (AESI) |  | Baseline to Week 40 | 
| Serum amlitelimab concentrations |  | Baseline to Week 40 | 
| Incidence of antidrug antibodies (ADAs) of amlitelimab |  | Baseline to Week 40 |