Inclusion Criteria:
Part 1:
1. Adults and adolescents (aged greater than or equal to \[\>=\] 12 to less than \[\<\] 18 at the time of informed consent form \[ICF\]/informed assent form \[IAF\] signature and weighing 40 \>= kilograms \[kg\]) who are candidates for systemic AD therapy.
2. Chronic AD (according to Hanifin and Rajka Criteria (Hanifin 1980)) that has been present for \>= 1 year before the screening visit.
3. EASI score \>= 12 at the Day 1/Baseline Visit.
4. IGA score \>= 3 (moderate) (scale of 0 \[clear\] to 4 \[severe\]) at the Day 1/Baseline visit.
5. \>= 10% BSA of AD involvement at the Day 1/Baseline visit.
6. History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable.
7. Completed electronic diary (eDiary) entries for pruritus and sleep-loss for a minimum of 4 of 7 days before Day 1/Baseline.
8. Willing and able to comply with all clinic visits and study-related procedures and questionnaires.
9. For women of childbearing potential: agree to remain abstinent (refrain from heterosexual intercourse) or to use a highly effective contraceptive method during the treatment period and for at least 4 weeks or 1 menstrual period after the last dose of lebrikizumab.
10. Participant must provide signed ICF. Adolescent participants must also provide separate informed assent to enroll in the study and sign and date either a separate IAF or the ICF signed by the parent/legal guardian (as appropriate based on local regulations and requirements).
Part 2:
11. Demonstrate clinical response to treatment at Week 24 of Part 1, defined as achieving EASI 75 or IGA 0/1 without the use of high-potency TCS within the prior 4 weeks or systemic corticosteroids at any time post baseline.
Exclusion Criteria:
1. Prior treatment at any time with tralokinumab, lebrikizumab, or an oral JAK inhibitor.
2. Intention to use any concomitant medication or therapy that is not permitted by this protocol or failure to undergo the required washout period for a particular prohibited medication.
3. History of anaphylaxis as defined by the Sampson criteria (Sampson 2006).
4. Uncontrolled chronic disease that might require bursts of oral corticosteroids, eg, comorbid severe uncontrolled asthma (defined by an Asthma Control Questionnaire-5 score \>= 1.5 or a history of \>= 2 asthma exacerbations within the last 12 months requiring systemic \[oral and/or parenteral\] corticosteroid treatment or hospitalisation for \>24 hours).
5. Occurrence of the following types of infection within 3 months before or during screening or development of these infections before Day 1/Baseline:
1. Serious (requiring hospitalisation, and/or IV or equivalent oral antibiotic treatment, as per the Investigator's opinion);
2. Opportunistic (as defined by Winthrop et al. (Winthrop 2015))
3. Chronic (duration of symptoms, signs, and/or treatment of 6 weeks or longer);
4. Recurring (including, but not limited to herpes simplex, herpes zoster, recurring cellulitis, chronic osteomyelitis).
6. Known current or chronic infection with any hepatitis virus.
7. Known liver cirrhosis and/or chronic hepatitis of any aetiology.
8. Known active endoparasitic infection or at high risk of these infections.
9. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g., tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per the Investigator's judgement.
10. History of human immunodeficiency virus (HIV) infection or known positive HIV serology.
11. Any clinically significant laboratory test results from the chemistry or haematology tests obtained at the Screening visit that would jeopardise the participants participation in the study, per the Investigator's judgement.
12. Presence of skin comorbidities that may interfere with study assessments.
13. History of malignancy, including mycosis fungoides, within 5 years before the Screening visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin with no evidence of recurrence in the past 12 weeks.
14. Severe concomitant illness(es) that in the Investigator's judgement would adversely affect the participation in the study. Any other medical or psychological condition that in the opinion of the Investigator may suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study participant because of his/her participation in this clinical trial, may make participation unreliable, or may interfere with study assessments.
15. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
16. Any known hypersensitivity or allergic response to lebrikizumab or any component of the investigational medicinal product (IMP).
17. For the scratch sensor substudy only: a history of allergic response to skin adhesives, active skin or systemic infection, active AD on the back of the hand, or a pre-existing sleep disorder, including insomnia, obstructive sleep apnea, or restless leg syndrome, or currently taking prescription sleep medications.
