Asthma
Conditions
Keywords
Inhaled corticosteroids (ICS), Post-Authorization, Baseline Blood eosinophil count (BEC), long-acting- β2 Agonist (LABA), Real-world participant population
Brief summary
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
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.
Interventions
DRUGTezepelumab
Participants will be receiving subcutaneous injection of tezepelumab.
Sponsors
AstraZeneca
Parexel
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 130 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Asthma Exacerbation Rate (AAER) | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | Asthma exacerbations were 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 was based on exacerbations reported by the investigator over 52 weeks. The exacerbation rate was compared between the 12-month period before \[baseline period (BP)\] and the 12-month period after initiation of tezepelumab \[up to study Week 52 (Visit 15) = study period (SP)\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Asthma Exacerbations | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | The number of participants with at least one asthma exacerbation in the 12-month period before (baseline period) and after initiation of tezepelumab (study period) (up to study Week 52 = study period) were assessed. |
| Number of Participants Who Completed the 52 -Week Study Period With Any Reduction in Total Number of Asthma Exacerbations | From Baseline period (Week -52 to Week 0) to Study period (Week 0 to Week 52) | The number of participants who completed the 52 -week study period following tezepelumab initiation with at least 50% reduction, and 100% reduction in total number of asthma exacerbations were assessed. |
| Cumulative Asthma Exacerbation Days | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | The cumulative asthma exacerbation days over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) was assessed. |
| Time to First Asthma Exacerbation | Baseline (Week 0) to Week 24 (Visit 8 = 6 months) and Week 52 (Visit 15 = 12 months) | The time to first exacerbation after initiation of tezepelumab was assessed. Data for median time to event have been presented for this endpoint. The median is the descriptive statistics median calculated using a subset of Participants with an event. |
| Rate of Asthma Exacerbations Associated With Hospitalizations | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | The rate of asthma exacerbations associated with hospitalization over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) was assessed. |
| Rate of Asthma Exacerbations Associated With Emergency Department /Urgent Care (ED/UC) Visits | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | The rate of asthma exacerbations associated with ED/UC visits over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) was assessed. |
| Rate of Asthma Exacerbations Associated With Hospitalizations or ED/UC Visits | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | 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) was assessed. |
| Number of Participants With Asthma Exacerbations Associated With Hospitalizations or ED/UC Visits | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | The number 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 = study period) were assessed. |
| Cumulative Asthma Exacerbation Days Associated With Hospitalizations or ED/UC Visits | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | The cumulative asthma exacerbation days associated with hospitalizations or ED/UC over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) were assessed. Total days of exacerbations resulting in hospitalizations or ED/UC visits have been presented. |
| Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) | Baseline (Week 0), Week 24 (Visit 8 = 6 months), Week 52 (Visit 15 = 12 months) | Lung function (FEV1) was measured pre-bronchodilator (pre-BD) by spirometry test. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration. |
| Change From Baseline in Pre-bronchodilator FEV1 | Baseline (Week 0) to Week 24 (Visit 8 = 6 months) and Week 52 (Visit 15 = 12 months) | Change from baseline in pre-bronchodilator FEV1 was assessed after initiation of tezepelumab. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration. |
| Number of Pre-BD FEV1 Responders | Week 24 (Visit 8 = 6 months), Week 52 (Visit 15 = 12 months) | Number of pre-BD FEV1 responders was defined as participants who achieved either at least 5% or 100 mL improvement from baseline. |
| Asthma Control Questionnaire (ACQ-6) | Baseline (Week 0), Week 24 (Visit 8 = 6 months), Week 52 (Visit 15 = 12 months) | The Asthma Control Questionnaire-6 (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), with higher scores indicating worse asthma control. The mean (average) ACQ-6 score is the mean of the responses. |
| Asthma Impairment and Risk Questionnaire (AIRQ) | Baseline (Week 0), Week 24 (Visit 8 = 6 months), Week 52 (Visit 15 = 12 months) | The Asthma Impairment and Risk Questionnaire (AIRQ) is a Patient Reported Outcome (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, ranging from 0 to 10, with higher scores indicating worse asthma control, where: 0-1 is well controlled, 2-4 is not well controlled, and 5-10 is very poorly controlled. |
| St. George's Respiratory Questionnaire (SGRQ) | Baseline (Week 0), Week 24 (Visit 8 = 6 months), Week 52 (Visit 15 = 12 months) | St. George's Respiratory Questionnaire (SGRQ) is a 50-item Patient Reported Outcome (PRO) instrument used to measure health status of participants with airway obstruction diseases. Questionnaire has 2 parts: part 1 consists of 8 items pertaining to severity of respiratory symptoms in preceding 4 weeks; part 2 consists of 42 items related to daily activity and psychosocial impacts of individual's respiratory condition. SGRQ yields a total score and 3 components scores (symptoms, activity, and impacts). Total score indicates impact of disease on overall health status, and it is expressed as percentage of overall impairment, in which 100 represents worst possible health status and 0 indicates best possible health status. Likewise, domain scores range from 0 to 100, with higher scores indicative of greater impairment. |
| Change From Baseline in ACQ-6 Score | Baseline (Week 0) to Week 24 (Visit 8 = 6 months) and Week 52 (Visit 15 = 12 months) | Change from baseline in Asthma Control Questionnaire-6 (ACQ-6) score was assessed. 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), with higher scores indicating worse asthma control. |
| Change From Baseline in AIRQ Score | Baseline (Week 0) to Week 24 (Visit 8 = 6 months) and Week 52 (Visit 15 = 12 months) | Change from baseline in Asthma Impairment and Risk Questionnaire (AIRQ) score was assessed. AIRQ is a Patient Reported Outcome (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, ranging from 0 to 10, with higher scores indicating worse asthma control, where: 0-1 is well controlled, 2-4 is not well controlled, and 5-10 is very poorly controlled. |
| Change From Baseline in SGRQ Score | Baseline (Week 0) to Week 24 (Visit 8 = 6 months) and Week 52 (Visit 15 = 12 months) | Change from baseline in St. George's Respiratory Questionnaire (SGRQ) score was assessed. SGRQ is a 50-item Patient Reported Outcome (PRO) instrument used to measure health status of participants with airway obstruction diseases. Questionnaire has 2 parts: part 1 consists of 8 items pertaining to severity of respiratory symptoms in preceding 4 weeks; part 2 consists of 42 items related to daily activity and psychosocial impacts of individual's respiratory condition. SGRQ yields a total score and 3 components scores (symptoms, activity, and impacts). Total score indicates impact of disease on overall health status, and it is expressed as percentage of overall impairment, in which 100 represents worst possible health status and 0 indicates best possible health status. Likewise, domain scores range from 0 to 100, with higher scores indicative of greater impairment. |
| Number of ACQ-6 Responders | Week 24 (Visit 8 = 6 months), Week 52 (Visit 15 = 12 months) | Number of ACQ-6 responders were assessed. Individual changes from baseline of ≥ 0.5 were considered to be clinically meaningful (minimum clinically important difference \[MCID\]). ACQ-6 responders in this study were defined as participants who achieved ≥ 1 MCID. |
| Number of AIRQ Responders | Week 24 (Visit 8 = 6 months), Week 52 (Visit 15 = 12 months) | Number of AIRQ responders were assessed. Individual changes from baseline of ≥ 2 were considered to be clinically meaningful (MCID). AIRQ responders in this study were defined as participants who achieved ≥ 1 MCID. |
| Number of SGRQ Responders | Week 24 (Visit 8 = 6 months), Week 52 (Visit 15 = 12 months) | Number of SGRQ responders were assessed. Individual changes from baseline of ≥ 4 were considered to be clinically meaningful (MCID). SGRQ (total and component score) responders in this study were defined as participants who achieved ≥ 1 MCID. |
| Number of Participants Who Require Any Systemic Corticosteroid (SCS) Use | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | Number 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) were assessed. |
| Cumulative Annualized SCS Dose | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | Cumulative annualized SCS dose in the 12-month periods before (baseline period) and after initiation of tezepelumab (up to study Week 52 = study period) were assessed. Cumulative annualized SCS dose for each participant was calculated as followed: Cumulative annualized SCS dose = \[sum of (cumulative SCS dose)/length of the planned treatment period\]\*365.25 |
| Number of Participants Who Require Longer-term (>30 Consecutive Days) SCS Use | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | Number 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) were assessed. |
| Number and Type of Asthma-related Healthcare Resource Utilization (HRU) | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | Number of participants with specific 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) were assessed. |
| Duration of Asthma-related Hospitalizations | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | 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) was assessed. |
| AAER for Asthma Exacerbations (Subgroups of Participants) | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | AAER based on asthma exacerbations in the 12-month period before \[baseline period (BP)\] and after initiation of tezepelumab \[up to study Week 52 = study period (SP)\] was assessed in following subgroups of participants: Blood eosinophil count (BEC) ≥300 cells/microliter; BEC \<300 cells/microliter; With clinically-relevant allergy to perennial aeroallergen; Without clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate chronic obstructive pulmonary disease (COPD); Significant smoking history (≥10 pack-years of smoking). |
| Number of Participants With Asthma Exacerbations (Subgroups of Participants) | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | The number of participants with at least one asthma exacerbations in the 12-month period before \[baseline period (BP)\] and after initiation of tezepelumab \[up to study Week 52 = study period (SP)\] were 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). |
| Number of Participants Who Completed the 52-week Study With Any Reduction in Total Number of Asthma Exacerbations (Subgroups of Participants) | From Baseline period (Week -52 to Week 0) to Study period (Week 0 to Week 52) | The number of participants who completed the 52-week study period following tezepelumab initiation with at least 50% reduction, and 100% reduction in total number of asthma exacerbations were 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). |
| Cumulative Asthma Exacerbation Days (Subgroups of Participants) | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | The cumulative asthma exacerbation days over 52 weeks before \[baseline period (BP)\] and after initiation of tezepelumab \[study period (SP)\] were 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). |
| Rate of Asthma Exacerbations Associated With Hospitalizations (Subgroups of Participants) | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | Rate of asthma exacerbations associated with hospitalization over 52 weeks before \[baseline period (BP)\] and after initiation of tezepelumab \[study period (SP)\] was assessed in the following subgroups of participants: BEC ≥300 cells/µL; BEC \<300 cells/µL; With a clinically-relevant allergy to perennial aeroallergen; Without a clinically-relevant allergy to 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). |
| Rate of Asthma Exacerbations Associated With Emergency Department/Urgent Care (ED/UC) Visits (Subgroups of Participants) | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | Rate of asthma exacerbations associated with ED/UC visits over 52 weeks before \[baseline period (BP)\] and after initiation of tezepelumab \[study period (SP)\] was assessed in following subgroups of participants: BEC ≥300 cells/µL; BEC \<300 cells/µL; With a clinically-relevant allergy to perennial aeroallergen; Without a clinically-relevant allergy to 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). |
| Rate of Asthma Exacerbations Associated With Hospitalizations or ED/UC Visits (Subgroups of Participants) | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | Rate of asthma exacerbations associated with hospitalizations or ED/UC visits over 52 weeks before \[baseline period (BP)\] and after initiation of tezepelumab \[study period (SP)\] was assessed in following subgroups of participants: BEC ≥300 cells/µL; BEC \<300 cells/µL; With clinically-relevant allergy to perennial aeroallergen; Without clinically-relevant allergy to 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). |
| Number and Type of Asthma-related HRU (Subgroups of Participants) | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | Number of participants with specific type of asthma related HRU in the 12-month period before \[baseline period (BP)\] and after initiation of tezepelumab \[up to study Week 52 = study period (SP)\] were 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). FEIA = Fluorescent enzyme immunoassay |
| Duration of Asthma-related Hospitalizations (Subgroups of Participants) | Baseline period (Week -52 to Week 0), Study period (Week 0 to Week 52) | Duration of asthma-related hospitalization in 12-month period before \[baseline period (BP)\] and after initiation of tezepelumab \[up to study Week 52 = study period (SP)\] was assessed in following subgroups of participants: BEC≥300 cells/µL; BEC\<300 cells/µL; With clinically-relevant allergy to perennial aeroallergen; Without clinically-relevant allergy to 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). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNjira Lugogo., MD.
University of Michigan Health. Michigan, USA
Participant flow
Recruitment details
The study was conducted from 29 April 2022 (first participant first visit) to 01 October 2025 (last participant last visit) at 32 study sites in the United States of America (USA).
Pre-assignment details
Participants who met the inclusion criteria and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of activities.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 52.9 years STANDARD_DEVIATION 16.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 259 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants |
| Race/Ethnicity, Customized Black or African American | 63 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants |
| Race/Ethnicity, Customized Not reported | 2 Participants |
| Race/Ethnicity, Customized Other | 5 Participants |
| Race/Ethnicity, Customized White | 204 Participants |
| Sex: Female, Male Female | 186 Participants |
| Sex: Female, Male Male | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 286 |
| other Total, other adverse events | 4 / 286 |
| serious Total, serious adverse events | 31 / 286 |
Outcome results
None listed