Study to Evaluate the Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma

Categorized percent reduction from baseline at Week 48. Percent change from baseline is defined as {final dose-baseline dose)/baseline dose}*100, and the categories of percent change from baseline in daily OCS dose are defined as: ≥90% to ≤100% reduction, ≥75% to <90% reduction, ≥50% to <75% reduction, >0% to <50% reduction, and, no change or any increase.

The annualized exacerbation rate is based on exacerbations reported by the investigator in the eCRF over 48 weeks.

Proportion (expressed as a percentage) of subjects with 100% reduction from baseline in daily OCS dose at Week 48. Percent change from baseline is defined as {(final dose-baseline dose)/baseline dose}*100.

Proportion (expressed as a percentage) of subjects with daily OCS dose ≤5 mg at Week 48.

Proportion (expressed as a percentage) of subjects with ≥50% reduction from baseline in daily OCS dose at Week 48. Percent change from baseline is defined as {(final dose-baseline dose)/baseline dose}*100.

Change from baseline in pre-BD FEV1 at Week 48. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration.

Change from baseline in Asthma Symptom Diary score at Week 48. 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. 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, where 0 indicates no asthma symptoms.

Change from baseline in weekly mean rescue medication use at Week 48. 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]. Each timepoint is calculated as weekly means based on daily diary data.

Change from baseline in weekly mean morning and evening peak expiratory flow (PEF) at Week 48. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Each timepoint is calculated as weekly means using at least 4 of the 7 days of PEF data.

Change from baseline in weekly mean number (expressed as a percentage) of night time awakenings at Week 48. Night-time awakenings percentage defined as number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data and multiplied by 100%. At least 4 out of 7 days of data is required to calculate a weekly mean.

Change from baseline in ACQ-6 at Week 48. 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.

Change from baseline in AQLQ(S)+12 as compared to placebo at Week 48. The AQLQ(S)+12 is a questionnaire that measures the health-related quality of life experienced by asthma subjects. 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).

Change from baseline in EQ-5D-5L at Week 48. The EQ-5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no/slight/moderate/severe/extreme problems) that reflect increasing levels of difficulty. The EQ-5D-5L scores are converted into a single index-based value (Health State Valuation), using the UK population-based weights. The Helth State Valuation is scored between 0 to 1, where higher score indicates a better health state.

Number of participants with asthma specific resource utilizations (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 48 weeks.

Change from baseline in WPAI+CIQ score at Week 48. The WPAI+CIQ consists of 10 questions about how asthma and asthma related issues impact a subject's ability to work, attend classes, and perform regular daily activities.

Work (Class) productivity loss is derived by sum of percentage of missed work (class hours) due to asthma and product of percentage of actual working hours (class) times degree of asthma affecting work (class) productivity while working. Percentage of missed work (class hours) due to asthma is calculated by number of hours missed work (class) due to asthma divided by total number of hours missed work (class) plus number of hours actually worked (in class).

Activity impairment is the degree health affected regular activities (other than work or class) rated from 0 to 10, with 0 meaning no effect, divided by 10, and then expressed as a percentage.

Change from baseline in fractional exhaled nitric oxide (FeNO) at week 48.

Change from baseline in blood eosinophil counts at week 48.

Change from baseline in total serum IgE at week 48.

Serum trough concentrations at each scheduled visit.

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.