A Study to Investigate Vaccine Responses in Subcutaneous Amlitelimab Treated Atopic Dermatitis Participants Aged 18 Years and Older Compared With Placebo

Study Overview
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Brief Summary
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This is a Phase 2, multicenter, randomized, double-blind placebo controlled, 2-arm study to evaluate the effect of amlitelimab on vaccine antibody responses, and the safety of amlitelimab concurrently administered with non-live vaccines in adult participants with moderate-to-severe atopic dermatitis (AD). The purpose of this study is to compare the immune responses to concomitantly administered Boostrix (tetanus, diphtheria, and acellular pertussis [Tdap]) and Pneumovax 23 (PPSV) vaccines in adult participants with moderate-to-severe AD treated with amlitelimab versus placebo. The study will evaluate the percentage of participants achieving a positive anti-tetanus response at Week 16 (primary endpoint) and a positive anti-pneumococcal response at Week 16 (primary endpoint). Study details include: The study duration will be up to 36 weeks (for participants not entering the LTS17367 [RIVER-AD]). The screening period will be 2 to 4 weeks. The treatment duration will be up to 16 weeks. The post-treatment safety follow-up period will be16 weeks. The number of visits will be up to 7 (or 6 for those entering LTS17367 [RIVER-AD]).

Detailed Description
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The study duration will be up to 36 weeks

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 2 Study to Evaluate the Effect of Amlitelimab on Vaccine Antibody Responses in Adult Participants With Moderate to Severe Atopic Dermatitis

Conditions
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Dermatitis Atopic

Intervention / Treatment
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* Drug: Amlitelimab
* Drug: Placebo
* Biological: Tdap vaccine
* Biological: PPS vaccine


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 Validated Investigator Global Assessment scale for atopic dermatitis (vIGA-AD) of 3 or 4 at baseline visit Eczema area and severity index (EASI) score of 12 or higher at baseline AD involvement of 10% or more of body surface area (BSA) at baseline Able and willing to comply with requested study visits and procedures Body weight ≥40 kg and ≤150 kg Exclusion Criteria: Skin co-morbidity that would adversely affect the ability to undertake AD assessments Receipt of any vaccine (expect influenza and COVID-19 vaccines) within 3 months prior to screening Receipt of any pneumococcal vaccine within approximate timeframe of 5 years prior to screening Prior receipt of two or more doses of Pneumovax 23 at any time Receipt of any tetanus-, diphtheria-, or pertussis-containing vaccine within approximate timeframe of 5 years prior to screening Participants for whom administration of the pneumococcal vaccine provided in this study is contraindicated or medically inadvisable, according to local label of the vaccine Participants for whom administration of the tetanus, diphtheria, and pertussis vaccine provided in this study is contraindicated or medically inadvisable, according to local label of the vaccine Having received any of the specified therapy within the specified timeframe(s) prior to the baseline visit Known history of or suspected significant current immunosuppression Any malignancies or history of malignancies prior to baseline (excluding in situ excised and cured cervical carcinoma, non-melanoma skin cancer excised and cured >3 years prior to baseline) History of solid organ or stem cell transplant Any active or chronic infection including helminthic infection requiring systemic treatment within 2 weeks prior baseline Positive for human immunodeficiency virus (HIV), Hepatitis B or hepatitis C at screening visit Participants with active tuberculosis (TB), latent TB, a history of incompletely treated TB, suspected extrapulmonary TB infection, or who are at high risk of contracting TB 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amlitelimab<br>Participants will receive amlitelimab and vaccines as per protocol. | Drug: Amlitelimab<br>* Subcutaneous injection in abdomen, outer thigh, or upper arm<br>Biological: Tdap vaccine<br>* Intramuscular (IM) injection into the deltoid muscle of the upper arm<br>Biological: PPS vaccine<br>* Intramuscular or subcutaneous injection into the deltoid muscle of the upper arm<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo matching amlitelimab and vaccines as per protocol. | Drug: Placebo<br>* Subcutaneous injection in abdomen, outer thigh, or upper arm<br>Biological: Tdap vaccine<br>* Intramuscular (IM) injection into the deltoid muscle of the upper arm<br>Biological: PPS vaccine<br>* Intramuscular or subcutaneous injection into the deltoid muscle of the upper arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with a positive tetanus response at Week 16 | Positive tetanus response is defined as a ≥4-fold increase from pre-vaccination at baseline in anti-tetanus immunoglobulin G [IgG] titer for participants with a pre-vaccination tetanus antibody titers ≥0.1 IU/mL or a titer of ≥0.2 IU/mL for participants with pre-vaccination titers of <0.1 IU/mL. | Week 16 | 
| Percentage of participants with a positive pneumococcal vaccine response at Week 16 | Positive pneumococcal vaccine response is defined as a ≥2-fold increase from baseline in anti-pneumococcal antibodies (APAb) against >50% of the 23 serotypes. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants who experienced treatment-emergent adverse events (TEAE), including serious adverse events (SAE) and adverse events of special interest (AESI) |  | Week 0 up to Week 32 | 
| Percentage of participants with potentially clinically significant abnormalities (PCSA) for vital signs and clinical laboratory assessments |  | Week 0 up to Week 32 | 
| Percentage of participants discontinued from study treatment due to TEAEs |  | Week 0 up to Week 32 | 
| Proportion of participants with validated Investigator Global Assessment scale for atopic dermatitis (vIGA-AD) of 0 (clear) or 1 (almost clear) and a reduction of ≥2 points from baseline at Week 16 | 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 16 | 
| Proportion of participants with a ≥75% reduction in EASI score (EASI-75) from baseline at Week 16 | The EASI is an Investigator-assessed validated tool used to measure the extent (area) and severity of AD using a 4-point scale; 0 (absent) to 3 (severe). | Week 16 | 
| Serum amlitelimab concentrations |  | Week 0 up to Week 16 | 
| Incidence of antidrug antibodies (ADAs) of amlitelimab |  | Week 0 up to Week 16 |