Inclusion Criteria:  AD as defined by the American Academy of Dermatology Consensus Criteria. History of AD for at least 12 months prior to baseline as determined by the Investigator through patient interview. Eczema Area and Severity Index (EASI) score ≥ 12 at screening and ≥ 16 at baseline. IGA score ≥ 3 (on the 0 to 4 IGA scale) at baseline. BSA of AD involvement ≥ 10% at baseline. Documented inadequate response or intolerance to TCS within 6 months prior to baseline visit Baseline PP-NRS score for maximum itch intensity ≥4. All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. For optional substudy only: Willingness to have 2 tape strips for comparison of baseline and treatment response.  Exclusion Criteria:  Skin comorbidities that may interfere with study assessments such as psoriasis, tinea corporis, lupus erythematosus. Conditions that may predispose the patient to excessive bleeding. Any other clinically significant disease, condition or medical history that, in the opinion of the Investigator, would interfere with participant safety, trial evaluations, and/or trial procedures. Laboratory abnormalities at the screening visit History of serious infections requiring intravenous therapy with the potential for recurrence or currently active moderate to severe infection at Screening (Grade 2 or higher) including active coronavirus disease 2019 (COVID-19). Live vaccine except Bacille Calmette Guerin-vaccination within 28 days prior to Day 1 or plan to receive one during the trial; Bacille Calmette Guerin-vaccination within 12 months prior to Screening. COVID-19 vaccine within 14 days prior to Study Day 1. Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate rilzabrutinib/placebo absorption. Initiation of prescription moisturizers (with or without additives such as ceramide, hyaluronic acid, urea, or filaggrin), topical anesthetics or antihistamines during the screening period. Use of TCS, calcineurin (tacrolimus, and/or pimecrolimus) or topical phosphodiesterase 4 inhibitor within 1 week prior to baseline and as concomitant medication. Use of systemic corticosteroids within 4 weeks prior to baseline and as concomitant medication. Phototherapy for AD or regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks prior to baseline or likely to be required as concomitant procedure during the study. Use of mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, dapsone, intravenous immunoglobulin (IVIG), Kineret (anakinra), Enbrel (etanercept), or any other immunosuppressant not mentioned in this exclusion criterion within 4 weeks prior to baseline. Use of infliximab, adalimumab, golimumab, abatacept, tocilizumab, certolizumab, secukinumab, IFN-γ, JAK inhibitors, dupilumab, and any other biologic or targeted-synthetic disease modifier drug not mentioned in this exclusion criterion or in exclusion criterion, as well as plasmapheresis within 12 weeks prior to baseline. Use of anti-CD20 drugs such as rituximab, ofatumumab, other long-acting biologics within 6 months prior to baseline (or shorter if there is documented B cell reconstitution for anti-CD20 drugs). Use of proton pump inhibitor drugs such as omeprazole and esomeprazole within 3 days of baseline (it is acceptable to change participant to H2 receptor blocking drugs prior to baseline). Concomitant use of known strong-to-moderate inhibitors and inducers of cytochrome P450 3A (CYP3A) within 14 days or 5 half-lives (whichever is longer) prior to baseline. Previous use of a BTK inhibitor. Has received any investigational drug (or is currently using an investigational device) within the 30 days before baseline, or at least 5 times the respective elimination half-life time (whichever is longer). Active TB or a history of incompletely treated TB, Quantiferon positive patients, Clinically significant abnormality consistent with prior/active TB infection based upon chest radiograph with at least posterior-anterior view, Suspected extrapulmonary TB infection, or patients at high risk of contracting TB.  The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.