Study to Evaluate Tezepelumab in Adults With Chronic Spontaneous UrticariaINCEPTION

- Signed informed consent must be obtained prior to participation in the study. - Male and female participants ≥ 18 years and ≤ 80 years of age at the time of screening. - Chronic spontaneous urticaria (CSU) diagnosis for ≥ 6 months at the time of screening. - CSU inadequately controlled by second generation H1-antihistamines (sgAH) at enrollment, as defined by all of the following: - The presence of itch and hives for >= 6 consecutive weeks at any time prior to screening visit 2 - Failure to respond to an sgAH (up to 4 times the approved dose) - Urticaria Activity Score over 7 days (UAS7) (range 0-42) >= 16 and Hives Severity Score over 7 days (HSS7) (range 0-21) >= 8 during the 7 days prior to enrollment - Participant with CSU who discontinued, is intolerant to, or was an inadequate responder to anti-IgE therapies despite being treated with omalizumab 300 mg every 4 weeks (Q4W) for 6 months or higher doses of omalizumab > 2 months or another anti-IgE therapy. Note: This criterion is only applicable for anti-IgE-experienced participants. - Participant willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedules. - Subject must have been on a sgAH at approved or increased doses (up to 4x the approved dose) for treatment of CSU for at least 3 consecutive days immediately prior to the day -14 screening visit (screening visit 2) and must have documented current use on the day of screening visit 1

Disease related, including but not limited to: - Urticaria is solely due to inducible urticaria - Active dermatologic diseases (or conditions) other than chronic urticaria, with urticaria wheals or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency) - Any other active skin disease associated with chronic itching that might influence, in the investigator’s opinion, the study evaluations and results (eg, atopic dermatitis, dermatitis herpetiformis, senile pruritus, etc.) - History of a clinically significant infection within 28 days prior to day 1 that, in the opinion of the investigator or medical monitor, might compromise the safety of the participant in the study, interfere with evaluation of the investigational product, or reduce the participants ability to participate in the study. - Evidence of active tuberculosis (TB) (in the opinion of the investigator), either treated or untreated, or a positive purified protein derivative (PPD) or QuantiFERON-TB Gold Plus (QFT-Plus) test for TB during screening. - History of malignancy, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy ≥ 12 months prior to screening or other malignancies treated with apparent success with curative therapy ≥ 5 years prior to screening visit 1. - Subject is unable to complete an electronic patient diary or complete questionnaires, or does not meet the required level of compliance with the eDiary during the 14 days sgAH stabilization period Other medical conditions - History or evidence of severe depression, schizophrenia, previous suicide attempts, or suicidal ideation. Prior/concomitant therapy, including but not limited to: - Treatment with any biologic products (eg, omalizumab, ligelizumab) within 4 months or 5 half-lives (whichever is longer) prior to screening visit 1 - Routine (daily or every other day for 5 or more consecutive days) use of systemic corticosteroids, systemic hydroxychloroquine, methotrexate, cyclosporine A, cyclophosphamide, tacrolimus, azathioprine, and mycophenolate mofetil within 30 days prior to screening visit 1. - Major surgery within 8 weeks prior to screening visit 1 or planned inpatient surgery or hospitalization during the study period. - Receipt of Ig or blood products within 30 days prior to screening visit 1. - Vaccination with a live or attenuated vaccine within 30 days prior to screening visit 1. Receipt of COVID-19 vaccines and inactive/killed vaccinations (eg, inactive influenza) are allowed, provided the vaccinations are not administered within 7 days before or after any study dosing visit. - Known hypersensitivity, including severe hypersensitivity reactions and/or history of anaphylactic shock, to any of the products or components to be administered during dosing or to products of similar chemical classes (ie, to murine, chimeric, or human antibodies.