A Study for Observing Severe Asthma in Patients Treated With Tezepelumab

Study Overview
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Brief Summary
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A study involving primary data collection within real-world settings of participants who initiate treatment with tezepelumab for severe uncontrolled asthma. This study will complement evidence obtained from randomized controlled trials and provide new data focusing on the holistic and patient reported outcome (PRO).

Detailed Description
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This is a 12-month, multi-country, multi-center, prospective, non-comparative and non-interventional (observational), post-reimbursement real-world evidence study that will assess asthma symptom control, lung function, and patient-reported outcomes including health-related quality of life after tezepelumab treatment initiation in participants with severe asthma in Europe and Canada. This study is planned to be conducted in several countries including but not limited to Canada, Germany, Denmark, Switzerland, and Sweden. Participants will be followed for a maximum period of 52 weeks after tezepelumab treatment initiation, irrespective of treatment discontinuation.

Official Title
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Asthma Control in Severe Asthma Patients Treated With Tezepelumab: A Prospective, Observational, Real-World Evidence Study (ASCENT)

Conditions
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Asthma

Intervention / Treatment
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* Other: None (Observational Study)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants aged 12 years or older Provision of signed and dated written informed consent, including assent for minors Prescribed treatment with Tezepelumab Diagnosis of asthma for at least 52 weeks prior to enrolment date and symptoms confirmed by the Investigator not to be due to alternative diagnoses Received at least one prescription of medium-dose to high-dose inhaled corticosteroids (ICS) during the 52 weeks prior to enrolment date Use of additional asthma maintenance controller medication(s) for at least 52 weeks prior to enrolment date Documented history of at least 1 asthma exacerbations during the 52 weeks prior to enrolment date Individuals with ACQ-6 score ≥ 1.5 (indicating inadequate asthma symptom control) at enrolment or up to 12 weeks before enrolment Participants currently receiving care from pulmonologists and/or allergists Participants who are able to understand and complete the ePROs Availability of participants medical records for asthma exacerbation and Healthcare Resource Utilization (HCRU) for the 52 weeks prior to Tezepelumab initiation Exclusion Criteria: Any contraindication to Tezepelumab Participants on concurrent biologics for asthma at the time of receiving the first dose of Tezepelumab will be excluded except for stable allergen immunotherapy (defined as a stable dose and regimen at the time of enrolment) Participation in an observational study that might, in the Investigator's opinion, influence the assessment for the current study, or participation in an interventional clinical trial in the last 3 months Pregnancy or lactation period.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prospective Cohort<br>Participants with severe uncontrolled asthma will receive tezepelumab. Relevant demographics, baseline clinical data, and asthma control questionnaire-6 (ACQ-6) will be retrospectively collected. All patient reported outcomes (PROs) will be prospectively collected. Other outcomes of interest (tezepelumab patterns of utilization, lung function, asthma exacerbations, medication use, and healthcare resource utilization [HRU]) will be collected at baseline (retrospective collection for 52-week pre-index period during enrolment) and prospectively collected during enrolment for participants who enroll into the study before the first dose of tezepelumab, and for a period of up to 52 weeks (at Weeks 4, 12, 24, and 52) after the index date. The index date is defined as the date when participants receive the first dose of tezepelumab. | Other: None (Observational Study)<br>* Not applicable since it's an observational study.<br>* Other names: Observational Study;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma Control Questionnaire (ACQ-6) score | Participant-reported asthma symptom control using ACQ-6 will be described. The ACQ-6 was developed for self-administration by adults and adolescents by omitting the forced expiration volume in 1 second (FEV1) % predicted question. Patients are asked to record their experience with 5 symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, and wheezing) and use of short-acting. β2 agonist over the previous week using a 7-point scale (0 = no impairment; 6 = maximum impairment). The ACQ-6 score is calculated by taking the mean of the 6 equally weighted items. The ACQ-6 score range is 0 (well controlled) to 6 (extremely poorly controlled). | Week 52 | 
| Change in Asthma Control Questionnaire 6 (ACQ-6) score from Baseline | Participant-reported asthma symptom control using ACQ-6 will be described. The minimum value of ACQ-6 score is 0 and the maximum value of ACQ-6 score is 6. The ACQ-6 score of 0 indicates well tolerated asthma whereas, the ACQ-6 score of 6 indicates extremely poorly controlled asthma | From Baseline (Week -52 to Week 0) to Week 52 | 
| Number of participants with improvement in ACQ-6 response score | Improvement from baseline in ACQ-6 score of >=0.5 will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Number of participants with well-controlled asthma (ACQ-6 score ≤ 0.75) | Participant-reported asthma symptom control using ACQ-6 will be described. | Week 52 | 
| Time to first ACQ-6 response | Time to first ACQ-6 response will be assessed. The ACQ-6 response is defined as change from baseline in ACQ-6 score <= -0.5. | From Baseline (Week -52 to Week 0) to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| St. George's Respiratory Questionnaire (SGRQ) total score | Asthma-specific health-related quality of life (HRQoL) will be described. The SGRQ is a 50-item PRO instrument developed to measure the health status of patients 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. | Week 52 | 
| Asthma Control Test (ACT) total score | Asthma-specific HRQoL will be described. The ACT is a questionnaire that assesses shortness of breath and general asthma symptoms, use of rescue medications, effect of asthma on daily functioning, and overall asthma control. Patients are asked to recall how their asthma has been during the past 4 weeks by responding to 5 questions on a scale of 1 to 5. The responses from the 5 items are summed to produce an ACT score that range from 5 (poorly controlled asthma) to 25 (well-controlled asthma). An ACT score ≥ 20 indicates well-controlled asthma, 16 to 19 indicates not well-controlled asthma, and ≤ 15 indicates very poorly controlled asthma. | Week 52 | 
| Change from baseline in SGRQ total score | Asthma-specific HRQoL will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Change from baseline in ACT total score | Asthma-specific HRQoL will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Number of participants with improvement in SGRQ total score | Improvement of ≥ 4 in SGRQ total score will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Number of participants with improvement in ACT total score | Improvement of ≥ 3 in ACT total score will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Pre-bronchodilator forced expiratory volume in 1 second (FEV1) | Lung function will be described. | Week 52 | 
| Post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) | Lung function will be described. | Week 52 | 
| Pre BD forced vital capacity (FVC) | Lung function will be described. | Week 52 | 
| Post-BD FVC | Lung function will be described. | Week 52 | 
| Pre-BD forced expiratory flow (FEF) | Lung function will be described. | Baseline (Week -52 to Week 0), Week 4, Week 24, and Week 52 | 
| Changes from baseline in pre-BD FEF | Lung function will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Changes from baseline in pre-BD FEV1 | Lung function will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Changes from baseline in post-BD FEV1 | Lung function will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Changes from baseline in pre-BD FVC | Lung function will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Changes from baseline in post-BD FVC | Lung function will be described | From Baseline (Week -52 to Week 0) to Week 52 | 
| Proportion of participants with spirometry and/or body plethysmography parameters | Participants will be assessed through spirometry and body plethysmography parameters | Week 52 | 
| Number of participants who achieve 5% or 100 mL improvement in pre-BD and post-BD FEV1 | Lung function will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Annualized asthma exacerbation rate (AAER) | Annual asthma exacerbation rate is calculated in years as total number of exacerbations of interest divided by the total time at risk. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Proportion of participants with asthma exacerbations | Asthma exacerbations will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Proportion of participants with reduced total number of asthma exacerbations | Proportion of participants with reduced total number of asthma exacerbations at the end of 52 weeks compared with baseline | From Baseline (Week -52 to Week 0) to Week 52 | 
| Proportion of participants who completed 52 weeks of tezepelumab treatment with at least 50% reduction in exacerbations | Asthma exacerbations will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Proportion of participants who completed 52 weeks of tezepelumab treatment without an asthma exacerbation | Asthma exacerbations in 52 weeks will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Change from baseline in AAER | Asthma exacerbations will be described. | Baseline (Week -52 to Week 0) to Week 52 | 
| Cumulative asthma exacerbation days | Asthma exacerbations in participants resulting in any hospitalization will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Proportion of participants with any systemic corticosteroid (SCS) or inhaled corticosteroid (ICS) use | Asthma related SCS or ICS use will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Number of participants with categorised percent reduction on cumulative systemic corticosteroids (SCS) dose | Percent reduction on cumulative SCS dose is categorized as follows: >=25%, >=50%, >75% and 100%. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Median SCS or ICS dose change | Asthma related SCS or ICS use will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Proportion of participants with long-term SCS and ICS use | Asthma related SCS or ICS use (>30 consecutive days) before and after tezepelumab initiation will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Time to earliest use SCS from tezepelumab initiation among patients that used SCS or ICS | Time to earliest use SCS from tezepelumab initiation among patients that used SCS or ICS will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Number and type of asthma related healthcare resource utilization (HCRU) | Asthma related HCRU will be described. | Baseline (Week -52 to Week 0), Week 4, Week 12, Week 24, and Week 52 | 
| Annualized rates of asthma-related visits leading to hospitalization and emergency department (ED) visits, urgent care visits, or unscheduled out-patient or physician visits | Asthma related HCRU will be described. | Baseline (Week -52 to Week 0), Week 4, Week 12, Week 24, and Week 52 | 
| Annualized rates of asthma related physician/healthcare calls/visits | Asthma related HCRU will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Duration of asthma-related hospitalisation | Asthma related HCRU will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Proportion of participants with stable disease | Asthma disease stability is a composite endpoint consisting of ACQ-6, FEV1, exacerbations, and OCS use. The participants achieve full disease stability when they reach a meaningful improvement in all 4 parameters which is maintained to the end of the follow-up period (Week 52). This includes ACQ-6 < 1.5, Pre-BD FEV1 at Week 52/pre-BD FEV1 at baseline >0.95, 50% reduction in annualized number of exacerbations in the follow-up period, and at least ≥50% reduction in OCS use in the follow-up period. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Duration (days) of tezepelumab treatment | Tezepelumab treatment features, including duration of therapy will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Proportion of participants with tezepelumab discontinuation and reason(s) | Tezepelumab treatment features, including discontinuation and reasons for discontinuation will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Proportion of participants with switching to other biologics for asthma and reasons(s) | Tezepelumab discontinuation and reasons for discontinuation will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 
| Time to tezepelumab discontinuation | Time taken to discontinue tezepelumab will be described. | From Baseline (Week -52 to Week 0) to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Real-World Evidence, Severe Uncontrolled Asthma, Inhaled corticosteroids (ICS), Post-Authorization