Effectiveness and Safety Study of Tezepelumab in Adults & Adolescent Participants With Severe Asthma in the United States

Study Overview
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Brief Summary
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To asses effectiveness and safety of tezepelumab in adult and adolescent participants with severe asthma including several under-studied populations in the United States.

Detailed Description
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This is a multicenter, single-arm, open-label, Post-authorization, Phase 4 study to assess the effectiveness of tezepelumab in the United States (US) among a real-world population of adults and adolescent participants with asthma requiring medium-dose to high-dose inhaled corticosteroids (ICS), with additional controller(s) for at least 12 months with documented history of at least 2 asthma exacerbations during the year prior to enrolment. The total duration of the study for each participant will be approximately 56 weeks. Approximately 400 participants will be enrolled. Participants will receive tezepelumab via subcutaneous injection at the study site, over a 48-week treatment period. The study also includes a post-dosing follow-up period from Weeks 48 to 52.

Official Title
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A Multicenter, Single-arm, Open-label, Post-Authorization, Phase 4 Effectiveness and Safety Study of Tezepelumab in Adult and Adolescent Participants With Severe Asthma Including Several Under-Studied Populations in the United States (PASSAGE)

Conditions
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Asthma

Intervention / Treatment
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* Drug: Tezepelumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participant must be 12 years of age or older, at the time of signing the informed consent form or assent. Documented physician-diagnosed asthma for at least 12 months prior to enrollment and confirmed by the Investigator not to be due to alternative diagnoses. Documented treatment with medium- to high dose ICS as per Global Initiative for Asthma (GINA) guidelines (GINA 2021) for at least 12 months prior to enrollment. Use of additional asthma maintenance controller medication(s) in addition to ICS for at least 12 months prior to enrollment. The additional maintenance controller medication may be contained in a combination product (eg, ICS/ long-acting β-agonist (LABA)). Documented history of at least 2 asthma exacerbations during the 12 months prior to enrollment. Physician decision that participant is eligible for treatment with tezepelumab according to the approved United States product insert (USPI). Currently receiving care from specialist physicians (eg, pulmonologists and/or allergists). Provision of signed and dated written informed consent form. Exclusion Criteria: Any contraindication to tezepelumab as per the US approved product label or in the opinion of the Investigator. Comorbid diagnosis of severe or very severe chronic obstructive pulmonary disease (COPD) per GOLD guidelines (GOLD 2021). Use of biologics that are approved for the treatment of asthma within 4 months or 5 half- lives (whichever is longer) prior to enrollment. Participation in an interventional clinical trial for asthma within 12 months prior to enrollment. Judgment by the Investigator that the participant is unlikely to comply with study procedures, restrictions, and requirements.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 130 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tezepelumab<br>Participants will be receiving 210 mg of tezepelumab every 4 weeks (Q4W) from Week 0 until Week 48. | Drug: Tezepelumab<br>* Participants will be receiving subcutaneous injection of tezepelumab.<br>* Other names: AMG 157 or MEDI9929;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized asthma exacerbation rate (AAER) | Asthma exacerbation will be defined by worsening of asthma symptoms that leads to temporary bolus/burst of systemic corticosteroids for at least 3 consecutive days, or an emergency department (ED) or urgent care visit due to asthma that required systemic corticosteroid (SCS), and/or inpatient hospitalization (≥24 hours) due to asthma. The AAER is based on exacerbations reported by the investigator over 52 weeks. The exacerbation rate will be compared between the 12 month period before (baseline period) and the 12 month period after initiation of tezepelumab (up to study Week 52 - study period). | Baseline period up to study Week 52 | 
| Proportion of participants with asthma exacerbations | The proportion of participants with asthma exacerbations in the 12 month periods before (baseline period) and after initiation of tezepelumab (study period) (up to study Week 52 - study period) will be assessed. | Baseline period up to study Week 52 | 
| Proportion of participants who completed the 52 -week study period with any reduction in total number of asthma exacerbations | The proportion of participants who completed the 52 -week study period following tezepelumab initiation with any reduction, at least 50% reduction, and 100% reduction in total number of asthma exacerbations will be assessed. | Baseline period up to study Week 52 | 
| Cumulative asthma exacerbation days | The cumulative asthma exacerbation days over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first asthma exacerbation | The time to first exacerbation after initiation of tezepelumab will be assessed. | Week 0 to Week 52 | 
| Rate of asthma exacerbations associated with hospitalizations | The rate of asthma exacerbations associated with hospitalization over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 | 
| Rate of asthma exacerbations associated with emergency department /urgent care (ED/UC) visits | The rate of asthma exacerbations associated with ED/UC visits over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 | 
| Rate of asthma exacerbations associated with hospitalizations or ED/UC visits over | The rate of asthma exacerbations associated with hospitalizations or ED/UC visits over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 | 
| Proportion of participants with asthma exacerbations associated with hospitalizations or ED/UC visits | The proportion of participants with asthma exacerbations associated with hospitalizations or ED/UC visits in in the 12-month periods before (baseline period) and after initiation of tezepelumab (study period) (up to study Week 52) will be assessed. | Baseline period up to study Week 52 | 
| Cumulative asthma exacerbation days associated with hospitalizations or ED/UC visits | The cumulative asthma exacerbation days associated with hospitalizations or ED/UC over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 | 
| Pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) | Lung function (FEV1) will be measured pre-bronchodilator (pre-BD) by spirometry test. | Baseline (Week 0), Week 24, Week 52 | 
| Change from baseline in pre-bronchodilator FEV1 | Change from baseline in pre-bronchodilator FEV1 will be assessed as lung function parameters after initiation of tezepelumab. | Baseline (Week 0), Week 24, Week 52 | 
| Proportion of pre-BD FEV1 responders | Proportion of pre-BD FEV1 responders is defined as participants who achieve either at least 5% or 100 mL improvement from baseline. | Baseline (Week 0), Week 24, Week 52 | 
| Asthma Control Questionnaire (ACQ-6) | The ACQ-6 is a shortened version of the ACQ that assesses the adequacy of asthma control and change in asthma control which occurs spontaneously or as a result of treatment. ACQ assesses symptoms and rescue bronchodilator use. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses. | Baseline (Week 0), Week 24, Week 52 | 
| Asthma Impairment and Risk Questionnaire (AIRQ) | The Asthma Impairment and Risk Questionnaire (AIRQ) is a PRO tool intended to identify participants 12 years and older whose health may be at risk because of uncontrolled asthma. It has 10 questions that ask about respiratory symptoms, activity limitation, sleep, rescue medication use, social activities, exercise, difficulty controlling asthma, and exacerbations. All items have a yes/no response option and the tool is scored by summing the total number of 'yes' responses. This sum score is used to assess level of asthma control where: 0-1 is well controlled, 2-4 is not well controlled, and 5-10 is very poorly controlled. Thus, a higher score indicates worse control status. | Baseline (Week 0), Week 24, Week 52 | 
| St. George's Respiratory Questionnaire (SGRQ) | The SGRQ is a 50-item PRO instrument developed to measure the health status of participants with airway obstruction diseases. The questionnaire is divided into 2 parts: part 1 consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The SGRQ yields a total score and 3 components scores (symptoms, activity, and impacts). 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. Likewise, the domain scores range from 0 to 100, with higher scores indicative of greater impairment. | Baseline (Week 0), Week 24, Week 52 | 
| Change from baseline in ACQ-6 score | Change from baseline in ACQ-6 score will be assessed. | Baseline (Week 0), Week 24, Week 52 | 
| Change from baseline in AIRQ score | Change from baseline in AIRQ score will be assessed. | Baseline (Week 0), Week 24, Week 52 | 
| Change from baseline in SGRQ score | Change from baseline in SGRQ score will be assessed. | Baseline (Week 0), Week 24, Week 52 | 
| Proportion of ACQ-6 responders | ACQ-6 responders are defined as participants who achieve >=1 clinically important difference (MCID). | Baseline (Week 0), Week 24, Week 52 | 
| Proportion of AIRQ responders | AIRQ responders is defined as participants who achieve ≥1 minimum clinically important difference (MCID). | Baseline (Week 0), Week 24, Week 52 | 
| Proportion of SGRQ responders | SGRQ responders is defined as participants who achieve ≥1 minimum clinically important difference (MCID). | Baseline (Week 0), Week 24, Week 52 | 
| Proportion of participants who require any systemic corticosteroid (SCS) use | Proportion of participants who require any SCS use in the 12-month periods before (baseline period) and after initiation of tezepelumab (up to study Week 52 -study period) will be assessed. | Baseline period up to study Week 52 | 
| Cumulative annualized SCS dose | Cumulative annualized SCS dose in the 12-month periods before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed. | Baseline period up to study Week 52 | 
| Proportion of participants who require longer-term (>30 consecutive days) SCS use | Proportion of participants who require longer-term (>30 consecutive days) SCS use in the 12-month periods before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed. | Baseline period up to study Week 52 | 
| Number and type of asthma-related healthcare resource utilization (HRU) | Number and type of asthma-related HRU in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed. | Baseline period up to study Week 52 | 
| Duration of asthma-related hospitalizations | Duration of asthma-related hospitalization in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52-study period) will be assessed. | Baseline period up to study Week 52 | 
| AAER for asthma exacerbations (subgroups of participants) | The AAER based on asthma exacerbations in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed in the following subgroups of participants: Blood eosinophil count (BEC) ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 | 
| Proportion of participants with asthma exacerbations (subgroups of participants) | The proportion of participants with asthma exacerbations in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 | 
| Proportion of participants who completed the 52 -week study with any reduction in total number of asthma exacerbations (subgroups of participants) | The proportion of participants who completed the 52 -week study period following tezepelumab initiation with any reduction, at least 50% reduction, and 100% reduction in total number of asthma exacerbations will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Week 0 to Week 52 | 
| Cumulative asthma exacerbation days (subgroups of participants) | The cumulative asthma exacerbation days over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 | 
| Rate of asthma exacerbations associated with hospitalizations (subgroups of participants) | The rate of asthma exacerbations associated with hospitalization over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 | 
| Rate of asthma exacerbations associated with emergency department urgent care (ED/UC) visits (subgroups of participants) | The rate of asthma exacerbations associated with ED/UC visits over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 | 
| Rate of asthma exacerbations associated with hospitalizations or ED/UC visits over (subgroups of participants) | The rate of asthma exacerbations associated with hospitalizations or ED/UC visits over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 | 
| Number and type of asthma-related HRU (subgroups of participants) | Number and type of asthma related HRU in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 | 
| Duration of asthma-related hospitalizations (subgroups of participants) | Duration of asthma-related hospitalization in the 12- month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inhaled corticosteroids (ICS), Post-Authorization, Baseline Blood eosinophil count (BEC), long-acting- β2 Agonist (LABA), Real-world participant population