An Open-label, DDI Study to Investigate the Effects of Amlitelimab on the PK of Selected Cytochrome P450 Substrates

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

• Male or female participant aged 18 to 65 years (inclusive), at the time of theinformed consent is signed.

• Participants must have AD as defined by the American Academy of DermatologyConsensus Criteria (2014) for 1 year or longer before signing of informed consent.

• The EASI score ≥16 at Screening and Check-in (Day -1).

• vIGA-AD score ≥3 (on the 0 to 4 vIGA-AD scale) at Screening and Check-in (Day -1).

• AD involvement of ≥10% body surface area at Screening and Check-in (Day -1).

• Participants must have documented history within 6 months prior to Screening andCheck-in (Day -1), of either inadequate response (including inadequate efficacy ormedical inadvisability) of topical treatments.

• Body weight within 40 to 150 kg at Screening and Day 1 and body mass index (BMI) <40kg/m2 (inclusive).

• Capable of giving signed informed consent.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Known history of significant immunosuppression or suspected current significantimmunosuppression, including history of invasive opportunistic, or helminthicinfections.

• Any malignancies or history of malignancies prior to baseline (except fornon-melanoma skin cancer that has been excised and cured for more than 5 years priorto baseline).

• Any concomitant illness that would, in the Investigator's opinion, inhibit theparticipant's participation in the study, including for example, but not limited to,hypertension, renal disease, neurological conditions, heart failure, and pulmonarydisease.

• Any medical condition which, in the Investigator's opinion may present anunreasonable risk to the study participants as a result of his/her participation inthis clinical study, may make participant's participation unreliable, or mayinterfere with study assessments.

• Any active or chronic infection including helminthic infection requiring systemictreatment within 4 weeks prior to baseline (1 week in the event of superficial skininfections) and any infection which as per Investigator's opinion precludes theparticipant's participation in the study or acute infection requiring treatment withsystemic antibiotics, antivirals, antiprotozoals, or antifungals at Screening orCheck--in (Day -1).

• History or presence of substance abuse (including alcohol, nicotine) prior toCheck-in (Day 1/V2) or regular alcohol consumption (>14 units per week for males and >7 units per week for females).

• In the Investigator's opinion, medical conditions related to prior AD medicationsthat have not healed/fully recovered for more than 2 weeks before the Screeningvisit, including, but not limited to, conjunctivitis, keratitis, eosinophilicconditions, arthralgia, herpes zoster, thrombosis.

• Use of tobacco- or nicotine-containing products within 6 months prior to Check-in (Day -1).

• Poor metabolizers for CYP2C9, CYP2C19, or CYP2D6 based on genotyping.

• Treatment with a live (attenuated) vaccine within 12 weeks prior to baseline;failure to complete non-live immunization required by local regulation (eg,vaccination for COVID-19) at least 14 days prior to baseline.

• Any contraindication to one or more of the following CYP cocktail studyinterventions, according to the applicable labeling:

• Caffeine

• Metoprolol

• Midazolam

• Omeprazole

• Warfarin

• Administration, within 14 days before baseline or within a period of 5 times theelimination half-life of the medication before baseline, whichever is longer, of anymedication that is a known inducer or inhibitor of either one or more of thefollowing CYP enzymes: CYP3A4, CYP2C19, CYP2C9, CYP2D6, and CYP1A2.

• Administration, within 14 days before baseline or within a period of 5 times theelimination half-life of the medication before baseline, whichever is longer, of:

• Caffeine

• Metoprolol

• Midazolam

• Omeprazole

• Warfarin.

• Consumption of any 1 or more of the following food items and/or beverages within 1week prior to baseline:

• Grapefruit or grapefruit juice, apple or apple juice, orange or orange juice,lemons or lemon juice, limes or lime juice

• Vegetables from the mustard green family (eg, broccoli)

• Charbroiled meats

• Caffeinated beverages, foods or drugs containing caffeine as well asdecaffeinated coffee.

Participants who are not willing to abstain from the consumption of these food items and/or beverages for certain periods during the study (Day 1 to Day 8, and Day 168 to Day 183) will also be excluded.

• History of excessive consumption of beverages containing caffeine (more than 4 cupsor glasses per day). Participants who are not willing to abstain from theconsumption of caffeine within 1 week prior to baseline, Day 1 to Day 8, and Day 168to Day 183 will also be excluded.

• Female participants who are using any form of hormonal contraceptives (eg, oral,injectables, implants, patches, rings, hormone-impregnated IUDs) for birth control.

• Have previously completed or withdrawn from this study or any other studyinvestigating amlitelimab or have previously received a dose of an investigationaldrug within the past 90 days or 5 half-lives, whichever is longer, prior to Check-in (Day -1).

• Concurrent participation in any other clinical study, including non-interventionalstudies.

• Participants positive for human immunodeficiency virus; participants with any of thefollowing results at Screening (Visit 1): presence of HBsAg with or without HBV DNAPCR test or presence of antibody to hepatitis B core antigen (HBcAb) or presence ofantibody to HBsAg with positive HBV DNA PCR test; positive hepatitis C totalantibody confirmed by positive Hepatitis C virus RNA.

• Known or suspected hypersensitivity to any of the study interventions (amlitelimab,CYP substrates [cocktail compounds]) or excipients, or drug or other allergy that,in the opinion of the Investigator, contraindicates participation in the study.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.