A Study to Evaluate the Effectiveness and Safety of Treatments, Either Alone or in Combination, for the Treatment of Moderate to Severe Atopic Dermatitis

Atopic dermatitis (AD) is a skin condition that may cause a rash and itching due to inflammation of the skin. The purpose of this study is to evaluate the clinical efficacy and safety of single therapies and/or combination therapies for moderate to severe AD through multiple substudies. This study will consist of multiple substudies. Substudy 1 will have a randomized, open-label period 1 followed by a lutikizumab treatment period 2 enrolling 80 participants at a 1 to 1 ratio. In Substudy 1, participants will receive subcutaneous (SC) injections of lutikizumab or matching placebo every other week for 16 weeks followed by an additional 32 weeks of SC injections of lutikizumab every other week for a total of 52 weeks. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and biomarker collections.

Inclusion Criteria: * Diagnosis of AD with onset of symptoms at least 1 year prior to the Baseline Visit and participant meets Hanifin and Rajka criteria. * Participant has applied non-medicated, additive-free bland emollient twice daily for at least 7 days before the Baseline Visit. * History of inadequate response to topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), or topical JAK inhibitors, OR systemic treatment for AD, OR participants for whom topical treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks). Exclusion Criteria: * Use of the following AD treatments within the specified washout period prior to the Baseline Visit: \-- Systemic therapy for AD, including but not limited to corticosteroids, methotrexate, cyclosporine, azathioprine, phosphodiesterase type 4 (PDE4) inhibitors, IFN-γ, and mycophenolate mofetil within 5 half-lives \[if known\] or within 4 weeks, whichever is longer; \-- Any biologic treatments, (within 5 half-lives \[if known\]) or within 12 weeks (whichever is longer), or as specified below: \< 8 weeks for dupilumab; \< 12 weeks for nemolizumab; \< 16 weeks for tralokinumab and lebrikizumab. * Phototherapy treatment, laser therapy, tanning booth, or extended sun exposure that could affect disease severity or interfere with disease assessments within 4 weeks. * Herbal treatments (e.g., traditional Chinese medicines) within 4 weeks. * Topical treatments (with the exception of non-medicated, additive-free bland emollients), including but not limited to TCS, TCIs, or topical PDE-4 inhibitors within 7 days. * Topical JAK inhibitor within 14 days. * Systemic JAK inhibitor (including but not limited to ruxolitinib, tofacitinib, baricitinib, upadacitinib, abrocitinib \[PF-04965842\], and filgotinib) within 5 half-lives \[if known\] or within 14 days, whichever is longer.