Tezepelumab

Change from baseline in total NPS evaluated by nasal endoscopy at Week 24 NPS: score 0-4 for each item, 4 indicates worse outcome

Change from baseline in bi-weekly mean nasal congestion score (NCS) evaluated as part of the Nasal Polyposis Symptom Diary (NPSD) at Week 24. NCS: score 0-3, 3 indicates worse outcome

Main Endpoints: Proportion of patients with at least one controller medication category reduction at the end of reduction phase (week 36) while sustaining asthma control * discontinuation of LTRA, or * discontinuation of LAMA, or * discontinuation of theophylline, or * Reduce inhale therapy to MD ICS/LABA, or * Reduce inhale therapy to LD ICS/LABA

The annualised moderate or severe COPD exacerbation rate (based on exacerbations reported by the investigator) up to 76 weeks treatment period compared to placebo.

Changes from baseline in participant-reported nasal congestion as evaluated by the nasal congestion score (NCS) as part of the nasal polyposis symptom diary (NPSD) following initiation of tezepelumab treatment.

changes from baseline in participant reported sino nasal symptoms as evaluated by sino nasal outcome test, 22 item (SNOT 22) total score following initiation of tezepelumab treatment.

Proportion of patients who reduced their SYMBICORT® daily maintenance dose without the loss of asthma control at the end of the step-down phase to either: Outside of the US: * Medium-dose maintenance and reliever therapy, or * Low-dose maintenance and reliever therapy, or * SYMBICORT® anti-inflammatory reliever only In the US: * Medium-dose SYMBICORT® and AIRSUPRA®,or * Low-dose SYMBICORT® and AIRSUPRA®, or * AIRSUPRA® only

To assess the effect of tezepelumab on severe asthma exacerbations in children 5 to \< 12 years old with severe uncontrolled asthma compared with placebo.

Peak esophageal eosinophil count per HPF determined by histological analysis of 2-4 biopsies from each of the proximal, mid, and distal esophagus.

The Dysphagia Symptom Questionnaire (DSQ) captures the presence and severity of dysphagia symptoms in the past day in a 4-item questionnaire. The DSQ score is calculated over 14-day periods and ranges from 0 to 84, with a lower score indicating less severe dysphagia.

The proportion (expressed as a percentage) of participants who discontinued OCS without loss of asthma control is presented. Loss of asthma control was defined as asthma worsening or exacerbation. Asthma worsening was defined by an increase of Asthma Control Questionnaire 6 (ACQ-6) score ≥0.5 from baseline. Asthma exacerbation was defined by worsening of asthma symptoms that led to temporary bolus/burst of systemic corticosteroids (SCS; or a temporary increase in stable OCS background dose) for at least 3 consecutive days (a single depo-injectable dose of corticosteroids being considered equivalent to a 3-day bolus/burst of SCS), and/or an emergency room (ER) or urgent care visit requiring SCS, and/or inpatient hospitalisation, both due to asthma.

The proportion (expressed as a percentage) of the participants who reduced daily prescribed maintenance OCS dose to ≤5 mg/day without loss of asthma control at Week 28 and Week 52 is presented.

Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.

Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed.

Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.

Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed.

Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.

Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. Vaccine immunogenicity analysis set consisted of all randomised patients who received the influenza vaccine plus at least 1 dose of tezepelumab or placebo, had pre and post vaccination HAI or MN antibody measurements, had no influenza infection prior to Visit 7 (Week 16), and had no protocol deviation, judged to have the potential to interfere with the generation or interpretation of an antibody response.

Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.

Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed.

Successful administration is defined as an injection completed, based on a used/returned (HCP or subject/caregiver) answer of YES to all 5 questions in the administration questionnaire, and satisfactory in vitro evaluation of returned/evaluated devices.

Includes adverse events with an onset date between the date of first dose of IP in the predecessor and minimum (date of last dose of IP + 33 days, date of death, date of study withdrawal, day prior to start of another biologic). The analysis is based on the Safety Analysis Set. Exposure adjusted rates are defined as number of subjects with AEs divided by total time at risk across all subjects, multiplied by 100

Includes time between the date of first dose of IP in the predecessor and minimum (date of last dose of IP + 33 days, date of death, date of study withdrawal, day prior to start of another biologic). The analysis is based on the Safety Analysis Set.

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.

A COPD exacerbation was defined as a change in the participant's usual COPD symptoms that is beyond normal day-to-day variation, is acute in onset, lasts 2 or more days, and may warrant a change in regular medication and leads to any of the following: Use of systemic corticosteroids for at least 3 days, use of antibiotics for at least 3 days, an inpatient hospitalisation due to COPD, or results in death. Analysis was done using a negative binomial model with the response variable as the number of COPD exacerbations experienced during the follow-up for exacerbations. The model included covariates of treatment group, region, and number of exacerbations reported at randomisation as recorded in IWRS (2, \>=3). The logarithm of the time at risk (in years) for exacerbation in the study is used as an offset variable.

The change from baseline to end of treatment (EOT) expressed as a ratio i.e. (EOT/baseline) in numbers of each of the airway submucosal inflammatory cells, determined by microscopic evaluation of bronchoscopic biopsies.

Blood samples were collected to determine the Cmax of tezepelumab. The Pharmacokinetic (PK) parameters were estimated using non-compartmental analysis method.

Blood samples were collected to determine the tmax of tezepelumab. The PK parameters were estimated using non-compartmental analysis method.

Blood samples were collected to determine the AUC0-last of tezepelumab and calculated by linear up/log down trapezoidal summation. The PK parameters were estimated using non-compartmental analysis method.

Blood samples were collected to determine the AUC0-inf of tezepelumab and calculated by linear up/log down trapezoidal summation and extrapolated to infinity by the addition of the last quantifiable concentration divided by the terminal rate constant. The PK parameters were estimated using non-compartmental analysis method.

Blood samples were collected to determine the t1/2 of tezepelumab and calculated as ln(2)/λZ, where λZ is the first-order rate constant associated with the terminal (log-linear) elimination phase. The PK parameters were estimated using non-compartmental analysis method.

Blood samples were collected to determine the CL/F of tezepelumab and estimated as dose divided by AUC0-inf. The PK parameters were estimated using non-compartmental analysis method.

Blood samples were collected to determine the Vss/F of tezepelumab and estimated as CL/F\*mean residence time (MRT), where MRT=Area under the moment curve of the analyte in the sampled matrix from zero (predose) extrapolated to infinite time/(AUC0-inf). The PK parameters were estimated using non-compartmental analysis method.

Blood samples were collected to determine the Vz/F of tezepelumab and estimated as CL/F\*1/ λZ. The PK parameters were estimated using non-compartmental analysis method.

To compare the AUCinf following single SC administration of tezepelumab using Vial-and-syringe, APFS, and AI.

To compare the Cmax following single SC administration of tezepelumab using vial-and-syringe, APFS, and AI.