Tezepelumab COPD Exacerbation Study

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.

Time frame: From randomisation up to Week 52

Population: Full analysis set under the primary estimand, which comprised all participants randomised to study treatment who received at least one dose and included all observed data over the 52-week period regardless of whether participants remained on randomised treatment and regardless of whether participants switched to an alternative biologic treatment.

An exacerbation was considered severe if it results in at least 1 of the following: Hospitalisation due to the COPD exacerbation (defined as a participant being admitted for ≥ 24 hours to an observation area, the emergency department, or other equivalent healthcare facility), or death related to COPD or COPD exacerbation.

Time frame: From randomisation up to Week 52

Population: Full analysis set under the primary estimand, which comprised all participants randomised to study treatment who received at least one dose and included all observed data over the 52-week period regardless of whether participants remained on randomised treatment and regardless of whether participants switched to an alternative biologic treatment.

The SGRQ is a 50-item PRO instrument to measure the health status of participants with airway obstruction diseases. The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. Baseline is the measurement recorded at Week 0 (Visit 3).

Time frame: Baseline and Week 52

Population: Number of participants analyzed is the number of participants with an observation at Week 52. All participants from the Full Analysis Set with at least one change from baseline value at any post baseline visit contributes to the analyses.

The CAT is an 8-item PRO developed to measure the impact of COPD on health status. A CAT total score is the sum of item responses. Scores range from 0-40 with higher scores indicative of greater COPD impact on health status. Baseline was defined as the value at the randomisation visit (Visit 3). If the Visit 3 measurement was missing, the screening value was used as baseline instead.

Time frame: Baseline and Week 52

Population: Number of participants analyzed is the number of participants with an observation at Week 52. All participants from the Full Analysis Set with at least one change from baseline value at any post baseline visit contributes to the analyses.

Pre-Bronchodilator FEV1 (L) was determined by spirometry at the clinic visit. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration. Change from baseline was obtained as an absolute difference between Week 52 measure and the baseline value. Baseline was defined as the last assessment recorded prior to the first dose of study treatment.

Time frame: Baseline and Week 52

Population: Number of participants analyzed is the number of participants with an observation at Week 52. All participants from the Full Analysis Set with at least one change from baseline value at any post baseline visit contributes to the analyses.

Blood samples were measured for the presence of ADAs for tezepelumab using validated assays. Treatment-induced ADA positive was defined as ADA negative at baseline and post-baseline ADA positive. Treatment-boosted ADA positive was defined as baseline positive ADA titre that was boosted to a 4 fold or higher level following IP administration. TE-ADA positive was defined as the sum of treatment-induced ADA positive and treatment-boosted ADA positive. ADA incidence is the proportion of TE-ADA positive subjects in a population. ADA persistently positive was defined as ADA positive at \>= 2 post-baseline assessments or ADA positive at last post-baseline assessment. ADA transiently positive was defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of ADA persistently positive. Treatment-induced nAb positive was defined as nAb negative or ADA negative at baseline and nAb positive at any post-baseline visit.

Time frame: Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled

Population: The safety analysis set included all subjects who received at least one dose of study drug.

The SGRQ is a 50-item PRO instrument to measure the health status of participants with airway obstruction diseases. The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. A responder was defined as an individual who had improvement at Week 52 (\>=4 point decrease in SGRQ total score).

Time frame: Baseline and Week 52

Population: Number of participants analyzed is the number of participants from the Full Analysis Set with a baseline SGRQ score.

An exacerbation event was defined as described in primary analysis. A participant was exacerbation free if they did not experience any moderate or severe exacerbations from randomisation to Week 52 (EOT).

Time frame: From randomisation up to Week 52

Population: Full analysis set under the primary estimand, which comprised all participants randomised to study treatment who received at least one dose and included all observed data over the 52-week period regardless of whether participants remained on randomised treatment and regardless of whether participants switched to an alternative biologic treatment.

An exacerbation was considered severe if it results in at least 1 of the following: Hospitalisation due to the COPD exacerbation (defined as a participant being admitted for ≥ 24 hours to an observation area, the emergency department, or other equivalent healthcare facility), or death related to COPD or COPD exacerbation.

Time frame: From randomisation up to Week 52

Population: Full analysis set under the primary estimand, which comprised all participants randomised to study treatment who received at least one dose and included all observed data over the 52-week period regardless of whether participants remained on randomised treatment and regardless of whether participants switched to an alternative biologic treatment.

Blood samples were collected to determine the serum concentration of Tezepelumab. With the exception of Week 0 and Week 64, only pre-dose data from samples collected between 21 and 35 days after previous dose of investigational product were included.

Time frame: Pre-dose at weeks 0, 4, 12, 24, 36 and also at weeks 52 and 64 where no dosing was scheduled

Population: The Pharmacokinetic (PK) analysis set comprises all subjects who received at least one dose of tezepelumab and have at least one detectable serum concentration post first dose that is not affected by factors such as protocol deviations (e.g. disallowed medication or incorrect study medication received).

Time to first moderate/severe COPD exacerbation post-randomisation, presented as number of subjects with at least one moderate/severe COPD exacerbation.

Time frame: From randomisation up to Week 52

Population: Full analysis set under the primary estimand, which comprised all participants randomised to study treatment who received at least one dose and included all observed data over the 52-week period regardless of whether participants remained on randomised treatment and regardless of whether participants switched to an alternative biologic treatment.

Time to first severe COPD exacerbation post-randomisation, presented as number of subjects with at least one severe COPD exacerbation.

Time frame: From randomisation up to Week 52

Population: Full analysis set under the primary estimand, which comprised all participants randomised to study treatment who received at least one dose and included all observed data over the 52-week period regardless of whether participants remained on randomised treatment and regardless of whether participants switched to an alternative biologic treatment.