Study to Evaluate Tezepelumab in Adults With Chronic Spontaneous Urticaria

Inclusion Criteria:

• 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 ofscreening.

• Chronic spontaneous urticaria (CSU) diagnosis for ≥ 6 months at the time ofscreening.

• CSU inadequately controlled by second generation H1-antihistamines (sgAH) atenrollment, as defined by all of the following:

• The presence of itch and hives for >= 6 consecutive weeks at any time prior toscreening 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 SeverityScore 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 inadequateresponder to anti-IgE therapies despite being treated with omalizumab 300 mg every 4weeks (Q4W) for 6 months or higher doses of omalizumab > 2 months or anotheranti-IgE therapy. Note: This criterion is only applicable for anti-IgE-experiencedparticipants.

• Participant willing and able to complete a daily symptom eDiary for the duration ofthe study and adhere to the study visit schedules.

• Subject must have been on a sgAH at approved or increased doses (up to 4x theapproved dose) for treatment of CSU for at least 3 consecutive days immediatelyprior to the day -14 screening visit (screening visit 2) and must have documentedcurrent use on the day of screening visit 1

Exclusion Criteria:

Disease related, including but not limited to:

• Urticaria is solely due to inducible urticaria

• Active dermatologic diseases (or conditions) other than chronic urticaria, withurticaria wheals or angioedema symptoms such as urticarial vasculitis, erythemamultiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquiredangioedema (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, atopicdermatitis, dermatitis herpetiformis, senile pruritus, etc.)

• History of a clinically significant infection within 28 days prior to day 1 that, inthe opinion of the investigator or medical monitor, might compromise the safety ofthe participant in the study, interfere with evaluation of the investigationalproduct, or reduce the participants ability to participate in the study.

• Evidence of active tuberculosis (TB) (in the opinion of the investigator), eithertreated or untreated, or a positive purified protein derivative (PPD) orQuantiFERON-TB Gold Plus (QFT-Plus) test for TB during screening.

• History of malignancy, except for basal cell carcinoma or in situ carcinoma of thecervix treated with apparent success with curative therapy ≥ 12 months prior toscreening 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 completequestionnaires, or does not meet the required level of compliance with the eDiaryduring 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 monthsor 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 systemiccorticosteroids, systemic hydroxychloroquine, methotrexate, cyclosporine A,cyclophosphamide, tacrolimus, azathioprine, and mycophenolate mofetil within 30 daysprior to screening visit 1.

• Major surgery within 8 weeks prior to screening visit 1 or planned inpatient surgeryor 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 screeningvisit 1. Receipt of COVID-19 vaccines and inactive/killed vaccinations (eg, inactiveinfluenza) are allowed, provided the vaccinations are not administered within 7 daysbefore or after any study dosing visit.

• Known hypersensitivity, including severe hypersensitivity reactions and/or historyof anaphylactic shock, to any of the products or components to be administeredduring dosing or to products of similar chemical classes (ie, to murine, chimeric,or human antibodies.