Study to Evaluate Tezepelumab in Adults With Chronic Spontaneous Urticaria

ABSTRACT

ConditionChronic Spontaneous Urticaria

InterventionBiological Tezepelumab Dose 1;Biological Tezepelumab Dose 2;Biological Omalizumab;Biological Placebo

Primary outcome:Change from Baseline in Urticaria Activity Score over 7 days (UAS7)

Criteria
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 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

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, 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.