Table 4.

Primary and secondary objectives and endpoints

Objective	Endpoint
Primary objective
Assess the effect of tezepelumab compared with placebo in reducing the prescribed OCS maintenance dose in adults with severe, uncontrolled asthma	Percentage reduction from baseline in daily OCS dose at week 48, defined as: 1. 90–100% reduction 2. 75–< 90% reduction 3. 50–< 75% reduction 4. 0–< 50% reduction 5. no change or any increase
Key secondary objective
Assess the effect of tezepelumab on asthma exacerbations compared with placebo	AAER • Time to first asthma exacerbation • Rate of asthma exacerbations associated with ER visits, urgent care visits or hospitalization • Proportion of subjects who did not experience an asthma exacerbation
Other secondary objectives
Assess the effect of tezepelumab on the prescribed OCS daily maintenance dose	Proportion of patients with 100% reduction from baseline in daily OCS dose at week 48 Proportion of patients with daily OCS dose ≤ 5 mg at week 48 Proportion of patients with ≥ 50% reduction from baseline in daily OCS dose at week 48
Assess the effect of tezepelumab on pulmonary function compared with placebo	Change from baseline in pre-BD FEV1
Assess the effect of tezepelumab on asthma symptoms and other asthma control metrics, compared with placebo	Change from baseline in: • weekly mean daily ASD score • weekly mean rescue medication use • weekly mean morning and evening PEF • weekly mean number of night-time awakenings • ACQ-6 score
Assess the effect of tezepelumab on asthma-related and general health-related quality of life compared with placebo	Change from baseline in: • AQLQ(S)+12 total score • EQ-5D-5L score
Assess the effect of tezepelumab on healthcare resource use and productivity loss owing to asthma	Asthma-specific resource use (e.g. unscheduled physician visits, use of other asthma medications) WPAI + CIQ scores
Assess the effect of tezepelumab on biomarkers	Change from baseline in FeNO, peripheral blood eosinophil count
Evaluate the pharmacokinetics and immunogenicity of tezepelumab	Pharmacokinetics: serum trough concentrations Immunogenicity: incidence of ADAs

AAER Annualized asthma exacerbation rate, ACQ-6 Asthma Control Questionnaire-6 items, ADA anti-drug antibody, AQLQ(S)+12 Asthma Quality of Life Questionnaire standardized for patients 12 years and older, ASD Asthma Symptom Diary, BD Bronchodilator, EQ-5D-5L 5-dimension 5-level EuroQol questionnaire, ER Emergency room, FeNO Fractional exhaled nitric oxide, FEV₁ forced expiratory volume in 1 s, OCS Oral corticosteroids, PEF Peak expiratory flow, WPAI + CIQ Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questionnaire