Study to Evaluate Tezepelumab in Adults With Severe Uncontrolled Asthma

The annual exacerbation rate is based on exacerbations reported by the investigator in the eCRF over 52 weeks

Mean change from baseline in FEV1 as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration.

Mean change from baseline in AQLQ(S)+12 as compared to placebo at Week 52. The AQLQ(S)+12 is a questionnaire that measures the health-related quality of life experienced by asthma participants. The total score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment).

Mean change from baseline in ACQ-6 as compared to placebo at Week 52. The ACQ-6 captures asthma symptoms and short-acting β2-agonist use via subject-report. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses.

Mean change from baseline in Asthma Symptom Diary score as compared to placebo at Week 52. The Asthma Symptom Diary comprises of 10 items (5 items in the morning; 5 items in the evening). Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the daily diary. A daily ASD score is the mean of the 10 items. A higher value indicates a worse outcome. Responses for all 10 items are required to calculate the daily ASD score; otherwise, it is treated as missing. For the 7-day average asthma symptom score, scoring is done with no imputation using the mean of at least 4 of the 7 daily ASD scores as a mean weekly item score. The 7-day average ASD score ranges from 0 to 4.

Time to the first occurrence of asthma exacerbation post randomization, presented as number of participants with at least one asthma exacerbation reported in the eCRF

Mean change from baseline in FENO (ppb) at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers

Number of participants with asthma specific resource utilization (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 52 weeks.

Mean serum trough PK concentrations taken pre-dose at each scheduled visit to evaluate the pharmacokinetics (PK) of tezepelumab

Mean change from baseline in EQ-5D-5L VAS at week 52. EQ-5D-5L visual analogue scale (VAS) allows participants to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.

Mean change from baseline in blood eosinophil counts at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers.

Mean change from baseline in IgE at week 52 to assess the effect of 210 mg of tezepelumab SC Q4W on biomarkers.

Mean change from baseline in night time awakenings due to asthma at Week 52. Night time awakenings percentage is defined as number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with available data and multiplied by 100%. At least 4 out of 7 days of data is required to calculate a weekly mean.

Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at >=2 post baseline assessments (with >=16 weeks between the first and the last positive) or positive at last post baseline assessment. Transiently positive is defined as having at least one post baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Treatment boosted ADA defined as baseline positive ADA that was boosted to a 4 fold or higher level following treatment. Treatment emergent ADA defined as sum of treatment induced ADA and treatment boosted ADA.

Daily rescue medication use is defined as: Number of night inhaler puffs + 2 x [number of night nebulizer times] + number of daytime inhaler puffs + 2 x [number of day nebulizer times]. Weekly means are calculated using at least 4 of 7 days of daily rescue medication use.

Mean change from baseline in home based morning PEF (L/min) at Week 52. Home PEF testing was performed by participant in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.

Mean change from baseline in home based evening PEF (L/min) at Week 52. Home PEF testing was performed by participant in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Weekly means are calculated using at least 4 of the 7 days of PEF data.

The annual exacerbation rate is based on exacerbations reported by the investigator that are associated with an emergency room visit, urgent care visit, or a hospitalization (where urgent care visit was captured as an emergency room visit on the eCRF).

The proportion of participants who had no asthma exacerbations is presented as the percentage of participants with no exacerbations. This is defined as participants who meet both the following criteria: (1) completed the 52 week treatment period and (2) did not report an exacerbation during this period.