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

• ClinicalTrials.gov Identifier: NCT05329194
• Recruitment Status: Recruiting
• First Posted: April 14, 2022
• Last Update Posted: June 6, 2023
• Sponsor: AstraZeneca
• Collaborator: Parexel
• Information provided by (Responsible Party): AstraZeneca

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: Tezepelumab	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 400 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: April 29, 2022
• Estimated Primary Completion Date: July 8, 2025
• Estimated Study Completion Date: July 8, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Tezepelumab; Participants will be receiving 210 mg of tezepelumab every 4 weeks (Q4W) from Week 0 until Week 48.	Drug: Tezepelumab; Participants will be receiving subcutaneous injection of tezepelumab.; Other Name: AMG 157 or MEDI9929

Outcome Measures

Primary Outcome Measures :

1. Annualized asthma exacerbation rate (AAER) [ Time Frame: Baseline period up to study Week 52 ]

   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).

2. Proportion of participants with asthma exacerbations [ Time Frame: Baseline period up to study Week 52 ]
   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.
3. 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 ]
   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.
4. Cumulative asthma exacerbation days [ Time Frame: Baseline period up to study Week 52 ]
   The cumulative asthma exacerbation days over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed.

Secondary Outcome Measures :

1. Time to first asthma exacerbation [ Time Frame: Week 0 to Week 52 ]
   The time to first exacerbation after initiation of tezepelumab will be assessed.
2. Rate of asthma exacerbations associated with hospitalizations [ Time Frame: Baseline period up to study Week 52 ]
   The rate of asthma exacerbations associated with hospitalization over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed.
3. Rate of asthma exacerbations associated with emergency department /urgent care (ED/UC) visits [ Time Frame: Baseline period up to study 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) will be assessed.
4. Rate of asthma exacerbations associated with hospitalizations or ED/UC visits over [ Time Frame: Baseline period up to study 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) will be assessed.
5. Proportion of participants with asthma exacerbations associated with hospitalizations or ED/UC visits [ Time Frame: Baseline period up to study Week 52 ]
   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.
6. Cumulative asthma exacerbation days associated with hospitalizations or ED/UC visits [ Time Frame: Baseline period up to study 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) will be assessed.
7. Pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) [ Time Frame: Baseline (Week 0), Week 24, Week 52 ]
   Lung function (FEV1) will be measured pre-bronchodilator (pre-BD) by spirometry test.
8. Change from baseline in pre-bronchodilator FEV1 [ Time Frame: Baseline (Week 0), Week 24, Week 52 ]
   Change from baseline in pre-bronchodilator FEV1 will be assessed as lung function parameters after initiation of tezepelumab.
9. Proportion of pre-BD FEV1 responders [ Time Frame: Baseline (Week 0), Week 24, Week 52 ]
   Proportion of pre-BD FEV1 responders is defined as participants who achieve either at least 5% or 100 mL improvement from baseline.
10. Asthma Control Questionnaire (ACQ-6) [ Time Frame: Baseline (Week 0), Week 24, Week 52 ]

    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.

11. Asthma Impairment and Risk Questionnaire (AIRQ) [ Time Frame: Baseline (Week 0), Week 24, Week 52 ]

    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.

12. St. George's Respiratory Questionnaire (SGRQ) [ Time Frame: Baseline (Week 0), Week 24, Week 52 ]

    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.

13. Change from baseline in ACQ-6 score [ Time Frame: Baseline (Week 0), Week 24, Week 52 ]
    Change from baseline in ACQ-6 score will be assessed.
14. Change from baseline in AIRQ score [ Time Frame: Baseline (Week 0), Week 24, Week 52 ]
    Change from baseline in AIRQ score will be assessed.
15. Change from baseline in SGRQ score [ Time Frame: Baseline (Week 0), Week 24, Week 52 ]
    Change from baseline in SGRQ score will be assessed.
16. Proportion of ACQ-6 responders [ Time Frame: Baseline (Week 0), Week 24, Week 52 ]
    ACQ-6 responders are defined as participants who achieve >=1 clinically important difference (MCID).
17. Proportion of AIRQ responders [ Time Frame: Baseline (Week 0), Week 24, Week 52 ]
    AIRQ responders is defined as participants who achieve ≥1 minimum clinically important difference (MCID).
18. Proportion of SGRQ responders [ Time Frame: Baseline (Week 0), Week 24, Week 52 ]
    SGRQ responders is defined as participants who achieve ≥1 minimum clinically important difference (MCID).
19. Proportion of participants who require any systemic corticosteroid (SCS) use [ Time Frame: Baseline period up to study Week 52 ]
    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.
20. Cumulative annualized SCS dose [ Time Frame: Baseline period up to study 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) will be assessed.
21. Proportion of participants who require longer-term (>30 consecutive days) SCS use [ Time Frame: Baseline period up to study Week 52 ]
    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.
22. Number and type of asthma-related healthcare resource utilization (HRU) [ Time Frame: Baseline period up to study Week 52 ]
    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.
23. Duration of asthma-related hospitalizations [ Time Frame: Baseline period up to study 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) will be assessed.
24. AAER for asthma exacerbations (subgroups of participants) [ Time Frame: Baseline period up to study Week 52 ]
    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).
25. Proportion of participants with asthma exacerbations (subgroups of participants) [ Time Frame: Baseline period up to study Week 52 ]
    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).
26. Proportion of participants who completed the 52 -week study with any reduction in total number of asthma exacerbations (subgroups of participants) [ Time Frame: Week 0 to Week 52 ]
    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).
27. Cumulative asthma exacerbation days (subgroups of participants) [ Time Frame: Baseline period up to study Week 52 ]
    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).
28. Rate of asthma exacerbations associated with hospitalizations (subgroups of participants) [ Time Frame: Baseline period up to study Week 52 ]
    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).
29. Rate of asthma exacerbations associated with emergency department urgent care (ED/UC) visits (subgroups of participants) [ Time Frame: Baseline period up to study 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) 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).
30. Rate of asthma exacerbations associated with hospitalizations or ED/UC visits over (subgroups of participants) [ Time Frame: Baseline period up to study 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) 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).
31. Number and type of asthma-related HRU (subgroups of participants) [ Time Frame: Baseline period up to study Week 52 ]
    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).
32. Duration of asthma-related hospitalizations (subgroups of participants) [ Time Frame: Baseline period up to study 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) 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).

Other Outcome Measures:

1. Number of participants with serious adverse events, adverse events that lead to tezepelumab treatment discontinuation, and adverse events of special interest [ Time Frame: Week 0 to Week 52 ]
   The safety and tolerability of tezepelumab will be assessed.

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 130 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

Locations

United States, Alabama

Research Site; Withdrawn

Hoover, Alabama, United States, 35244

Research Site; Withdrawn

Mobile, Alabama, United States, 36608

United States, Arizona

Research Site; Withdrawn

Gilbert, Arizona, United States, 85234

United States, California

Research Site; Not yet recruiting

La Jolla, California, United States, 92093

Research Site; Recruiting

Westminster, California, United States, 92683

Research Site; Recruiting

Whittier, California, United States, 90603

United States, Colorado

Research Site; Recruiting

Colorado Springs, Colorado, United States, 80907

United States, Connecticut

Research Site; Not yet recruiting

New Haven, Connecticut, United States, 06510

United States, District of Columbia

Research Site; Not yet recruiting

Washington, District of Columbia, United States, 20037

United States, Illinois

Research Site; Not yet recruiting

Chicago, Illinois, United States, 60611

United States, Kentucky

Research Site; Recruiting

Lexington, Kentucky, United States, 40509

United States, Louisiana

Research Site; Not yet recruiting

New Orleans, Louisiana, United States, 70112

United States, Maryland

Research Site; Recruiting

Upper Marlboro, Maryland, United States, 20772

Research Site; Withdrawn

White Marsh, Maryland, United States, 21162

United States, Michigan

Research Site; Recruiting

Ann Arbor, Michigan, United States, 48109

Research Site; Recruiting

Ypsilanti, Michigan, United States, 48197

United States, Minnesota

Research Site; Recruiting

Saint Paul, Minnesota, United States, 55109

United States, Missouri

Research Site; Recruiting

Saint Louis, Missouri, United States, 63110

United States, Nebraska

Research Site; Recruiting

Lincoln, Nebraska, United States, 68505

Research Site; Recruiting

Omaha, Nebraska, United States, 68114

United States, New York

Research Site; Withdrawn

Bronx, New York, United States, 10465

Research Site; Recruiting

Hollis, New York, United States, 11423

Research Site; Withdrawn

Horseheads, New York, United States, 14845

Research Site; Recruiting

Rochester, New York, United States, 14642

Research Site; Recruiting

Valhalla, New York, United States, 10595

United States, North Carolina

Research Site; Recruiting

Chapel Hill, North Carolina, United States, 27514

Research Site; Withdrawn

Durham, North Carolina, United States, 27709

United States, Ohio

Research Site; Withdrawn

Cincinnati, Ohio, United States, 45229

Research Site; Recruiting

Toledo, Ohio, United States, 43617

United States, Oklahoma

Research Site; Recruiting

Oklahoma City, Oklahoma, United States, 73120

United States, Pennsylvania

Research Site; Recruiting

Altoona, Pennsylvania, United States, 16602

Research Site; Recruiting

Philadelphia, Pennsylvania, United States, 19140

United States, Rhode Island

Research Site; Recruiting

Warwick, Rhode Island, United States, 02886

United States, South Carolina

Research Site; Recruiting

Greenville, South Carolina, United States, 29607

United States, Texas

Research Site; Withdrawn

Dallas, Texas, United States, 75246

Research Site; Recruiting

Fort Worth, Texas, United States, 76107

Research Site; Recruiting

McKinney, Texas, United States, 75069

Research Site; Recruiting

San Antonio, Texas, United States, 78229

United States, Virginia

Research Site; Not yet recruiting

Charlottesville, Virginia, United States, 22903

United States, Washington

Research Site; Recruiting

Vancouver, Washington, United States, 98664

United States, Wisconsin

Research Site; Withdrawn

Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

AstraZeneca

Parexel

Investigators

• Principal Investigator: Njira Lugogo., MD.; University of Michigan Health. Michigan, USA

More Information

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT05329194
• Other Study ID Numbers: D5180C00032
• First Posted: April 14, 2022
• Last Update Posted: June 6, 2023
• Last Verified: June 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by AstraZeneca:

Inhaled corticosteroids (ICS); Post-Authorization; Baseline Blood eosinophil count (BEC); long-acting- β2 Agonist (LABA); Real-world participant population

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases