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

AstraZeneca287 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

287

Conditions

Asthma

Interventions

TezepelumabDRUG

Participants will be receiving subcutaneous injection of tezepelumab.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 130 Years

Medical Language ↔ Plain English

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.

Locations (37)

Outcomes

Primary Outcomes

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).

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: Baseline period up to study Week 52

Secondary Outcomes

Time to first asthma exacerbation

The time to first exacerbation after initiation of tezepelumab will be assessed.

Data from ClinicalTrials.gov

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Research Site

Mobile, Alabama, United States

Research Site

Gilbert, Arizona, United States

Research Site

Long Beach, California, United States

Research Site

Los Angeles, California, United States

Research Site

Rancho Mirage, California, United States

Research Site

Westminster, California, United States

Research Site

Colorado Springs, Colorado, United States

Research Site

New Haven, Connecticut, United States

Research Site

Washington D.C., District of Columbia, United States

Research Site

Chicago, Illinois, United States

...and 27 more locations

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline (Week 0), Week 24, Week 52

Change from baseline in ACQ-6 score

Change from baseline in ACQ-6 score will be assessed.

Time frame: Baseline (Week 0), Week 24, Week 52

Change from baseline in AIRQ score

Change from baseline in AIRQ score will be assessed.

Time frame: Baseline (Week 0), Week 24, Week 52

Change from baseline in SGRQ score

Change from baseline in SGRQ score will be assessed.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: Baseline period up to study Week 52