Study to Evaluate Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adult Patients With Severe Asthma (WAYFINDER)

A Multicentre, Single-arm, Phase 3b Efficacy and Safety Study of Tezepelumab 210 mg Administered Subcutaneously to Reduce Oral Corticosteroid Use in Adult Participants With Severe Asthma on High-dose Inhaled Corticosteroid Plus Long-acting β2 Agonist and Long-term Oral Corticosteroid Therapy (WAYFINDER)

This is a study designed to evaluate efficacy and safety of Tezepelumab in reducing oral corticosteroid use in adult patients with severe asthma who are receiving oral corticosteroids with or without additional asthma controller medications.

Study Overview

• Status: Active, not recruiting
• Conditions: Asthma
• Intervention / Treatment: Biological: Tezepelumab

Detailed Description

This is a multicentre, single-arm, phase 3b study designed to evaluate efficacy and safety of reducing daily oral corticosteroid use after initiation of 210 mg dose of Tezepelumab administered subcutaneously in patients with severe asthma receiving high-dose inhaled corticosteroid plus long-acting β2 agonist and oral corticosteroids with or without additional asthma controller medications.

• Study Type: Interventional
• Enrollment (Actual): 306
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1121ABE
    • Research Site
  • Caba, Argentina, C1012AAR
    • Research Site
  • Caba, Argentina, 1426
    • Research Site
  • Florencio Varela, Argentina, 1888
    • Research Site
  • Mendoza, Argentina, M5500GHB
    • Research Site
  • Monte Grande, Argentina, 1842
    • Research Site
  • Pilar, Argentina, 1629
    • Research Site
  • Quilmes, Argentina, B1878FNR
    • Research Site
  • Ranelagh, Argentina, 1886
    • Research Site
  • Rosario, Argentina, 2000
    • Research Site
  • San Fernando, Argentina, B1646EBJ
    • Research Site
  • San Miguel de Tucuman, Argentina, 4000
    • Research Site
• Belgium
  • Brussels (Woluwé-St-Lambert), Belgium, 1200
    • Research Site
  • Erpent, Belgium, 5101
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
• Bulgaria
  • Haskovo, Bulgaria, 6305
    • Research Site
  • Razgrad, Bulgaria, 7200
    • Research Site
  • Sofia, Bulgaria, 1431
    • Research Site
  • Sofia, Bulgaria, 1142
    • Research Site
  • Sofia, Bulgaria, 5000
    • Research Site
  • Velika Tarnovo, Bulgaria, 5250
    • Research Site
• France
  • Antony, France, 92160
    • Research Site
  • Bordeaux, France, 33076
    • Research Site
  • Brest Cedex, France, 29609
    • Research Site
  • Lyon, France, 69004
    • Research Site
  • Marseille, France, 13915
    • Research Site
  • Montpellier, France
    • Research Site
  • Nantes, France, 44000
    • Research Site
  • Nice, France, 06000
    • Research Site
• Germany
  • Berlin, Germany, 12203
    • Research Site
  • Darmstadt, Germany, 64283
    • Research Site
  • Fürstenwalde/Spree, Germany, 15517
    • Research Site
  • Mainz, Germany, 55128
    • Research Site
  • Reinfeld (Holstein), Germany, 23858
    • Research Site
• Latvia
  • Daugavpils, Latvia, LV-5410
    • Research Site
  • Daugavpils, Latvia, LV-5417
    • Research Site
  • Jurmala, Latvia, LV-2015
    • Research Site
  • Kyiv, Latvia, 04050
    • Research Site
  • Riga, Latvia, LV1002
    • Research Site
  • Riga, Latvia, LV-1011
    • Research Site
  • Valmiera, Latvia, LV-4201
    • Research Site
• Mexico
  • Chihuahua, Mexico, 31200
    • Research Site
  • Chihuahua, Mexico, 31000
    • Research Site
  • Guadalajara, Mexico, 44100
    • Research Site
  • Monterrey, Mexico, 64360
    • Research Site
• Poland
  • Bychawa, Poland, 23100
    • Research Site
  • Chmielnik, Poland, 26-020
    • Research Site
  • Gdańsk, Poland, 80-952
    • Research Site
  • Kraków, Poland, 31-011
    • Research Site
  • Ostrowiec Świętokrzyski, Poland, 27-400
    • Research Site
  • Sosnowiec, Poland, 41-200
    • Research Site
  • Wroclaw, Poland, 54-239
    • Research Site
  • Wroclaw, Poland, 50-044
    • Research Site
  • Wroclaw, Poland, 53-301
    • Research Site
  • Łódź, Poland, 92-213
    • Research Site
• Spain
  • Badalona, Spain, 08916
    • Research Site
  • Barcelona, Spain, 8035
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Oviedo, Spain, 33011
    • Research Site
  • Santander, Spain, 39008
    • Research Site
  • Sevilla, Spain, 41009
    • Research Site
  • Tenerife, Spain, 38010
    • Research Site
• United Kingdom
  • Belfast, United Kingdom, BT7 1NN
    • Research Site
  • Bradford, United Kingdom, BD9 6RJ
    • Research Site
  • Le3 9qp, United Kingdom
    • Research Site
  • London, United Kingdom, SE1 7EH
    • Research Site
  • London, United Kingdom, SW3 6HP
    • Research Site
  • Nottingham, United Kingdom, NG5 1PB
    • Research Site
  • Portsmouth, United Kingdom, PO6 3LY
    • Research Site
• United States
  • California
    • Newport Beach, California, United States, 92663
      • Research Site
  • Delaware
    • Newark, Delaware, United States, 19713
      • Research Site
  • Florida
    • Loxahatchee Groves, Florida, United States, 33470
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Research Site
  • New York
    • Bronx, New York, United States, 10467
      • Research Site
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main inclusion criteria:

• Age 18-80 years.
• Documented physician diagnosed asthma requiring continuous treatment with high-dose ICS plus a LABA for at least 6 months prior to Visit 1. The ICS and LABA can be contained within a combination product or given by separate inhalers.
• Documented long-term OCS therapy for asthma, equivalent to a daily dose of at least 5 mg and up to 40 mg of prednisone/prednisolone for at least 3 continuous months directly preceding Visit 1.
• Participant should be on a stable maintenance OCS dose for at least 4 weeks prior to Visit 1.
• Documented history of at least 1 asthma exacerbation event within 12 months prior to Visit 1.

Other inclusion criteria per protocol apply.

Main exclusion criteria:

• Pulmonary disease or systemic diseases, other than asthma associated with elevated peripheral EOS counts.
• Any disorder or major physical impairment that is not stable and could affect the safety of the participant throughout the study, influence the findings of the study or the interpretation, or impede the participant's ability to complete the entire duration of study.
• History of cancer.
• History of a clinically significant infection requiring treatment with antibiotics, antiviral or additional corticosteroid medications finalised < 2 weeks before Visit 1.
• A helminth parasitic infection diagnosed within 6 months prior to Visit 1 that has not been treated with, or has failed to respond to, standard of care therapy.
• Current smokers or participants with smoking history ≥ 10 pack-years and participants using vaping products, including electronic cigarettes.
• History of chronic alcohol or drug abuse within 12 months prior to Visit 1.
• Tuberculosis requiring treatment within the 12 months prior to Visit 1.
• History of known immunodeficiency disorder including a positive HIV test at Visit 1.
• Major surgery within 8 weeks prior to Visit 1 or planned surgical procedures requiring general anaesthesia or inpatient status for > 1 day during the conduct of the study.
• Coexistent inflammatory conditions for which long-term OCS doses are part of their maintenance treatment.
• Receipt of any marketed or investigational biologic agent within 4 months or 5 half-lives (whichever is longer) prior to Visit 1 or receipt of any investigational nonbiologic agent within 30 days or 5 half-lives (whichever is longest) prior to Visit 1. Participants enrolled in current or previous tezepelumab studies will not be included.
• Concurrent enrolment in another clinical study involving an IP.
• Treatment with systemic immunosuppressive/immunomodulating drugs, except for OCS used in the treatment of asthma/asthma exacerbations, within the last 12 weeks or 5 half-lives (whichever is longer) prior to Visit 1.
• History of anaphylaxis or documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy.
• Positive hepatitis B surface antigen, or hepatitis C virus antibody serology at screening, or a positive medical history for hepatitis B or C.
• Pregnant, breastfeeding, or lactating women.

Other exclusion criteria per protocol apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tezepelumab; Tezepelumab subcutaneous injection	Biological: Tezepelumab; Tezepelumab subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants who discontinued OCS without loss of asthma control	Proportion of participants who discontinued OCS without loss of asthma control at Week 28.	At Week 28
Proportion of participants who discontinued OCS without loss of asthma control	Proportion of participants who discontinued OCS without loss of asthma control at Week 52.	At Week 52
Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control	Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control at Week 28.	At Week 28
Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control	Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control at Week 52.	At Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Annualised Asthma Exacerbation Rate	The annualised asthma exacerbation rate is based on exacerbations reported by investigator in eCRF over 28 weeks.	Baseline to Week 28
The Annualised Asthma Exacerbation Rate	The annualised asthma exacerbation rate is based on exacerbations reported by investigator in eCRF over 52 weeks.	Baseline to Week 52
Rate of asthma exacerbation associated with hospitalisation or emergency room (ER)	Rate of asthma exacerbation is based on exacerbations reported by the investigator in eCRF that are associated with a hospitalization or an emergency room visit over 28 weeks.	Baseline to Week 28
Rate of asthma exacerbation associated with hospitalisation or emergency room (ER)	Rate of asthma exacerbation is based on exacerbations reported by the investigator in eCRF that are associated with a hospitalization or an emergency room visit over 52 weeks.	Baseline to Week 52
Rate of asthma exacerbation associated with hospitalisation	Rate of asthma exacerbation is based on exacerbations reported by the investigator in eCRF that are associated with a hospitalization over 28 weeks.	Baseline to Week 28
Rate of asthma exacerbation associated with hospitalisation	Rate of asthma exacerbation is based on exacerbations reported by the investigator in eCRF that are associated with a hospitalization over 52 weeks.	Baseline to Week 52
Proportion of participants who did not experience an exacerbation	Proportion of participants who did not experience an exacerbation over 28 weeks.	Baseline to Week 28
Proportion of participants who did not experience an exacerbation	Proportion of participants who did not experience an exacerbation over 52 weeks.	Baseline to Week 52
Proportion of participants who did not experience an exacerbation associated with hospitalisation or ER visit	Proportion of participants who did not experience an exacerbation associated with hospitalization or ER visit over 28 weeks.	Baseline to Week 28
Proportion of participants who did not experience an exacerbation associated with hospitalisation or ER visit	Proportion of participants who did not experience an exacerbation associated with hospitalization or ER visit over 52 weeks.	Baseline to Week 52
Proportion of participants who did not experience an exacerbation associated with hospitalisation	Proportion of participants who did not experience an exacerbation associated with hospitalization over 28 weeks.	Baseline to Week 28
Proportion of participants who did not experience an exacerbation associated with hospitalisation	Proportion of participants who did not experience an exacerbation associated with hospitalization over 52 weeks.	Baseline to Week 52
Proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose	Proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose at Week 28. Percent change from baseline is defined as {(final dose-baseline dose)/baseline dose}*100.	Baseline to Week 28
Proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose	Proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose at Week 52. Percent change from baseline is defined as {(final dose-baseline dose)/baseline dose}*100.	Baseline to Week 52
Categorised percent reduction from baseline in the daily maintenance OCS dose	Categorised percent reduction from baseline in the daily maintenance OCS dose at Week 28. Percent change from baseline is derived as {(final dose-baseline dose)/baseline dose}*100 and the categories of percent change from baseline are defined as ≥ 90% to ≤ 100% reduction, ≥ 75% to < 90% reduction, ≥ 50% to < 75% reduction, > 0% to < 50% reduction, no change or any increase.	Baseline to Week 28
Categorised percent reduction from baseline in the daily maintenance OCS dose	Categorised percent reduction from baseline in the daily maintenance OCS dose at Week 52. Percent change from baseline is derived as {(final dose-baseline dose)/baseline dose}*100 and the categories of percent change from baseline are defined as ≥ 90% to ≤ 100% reduction, ≥ 75% to < 90% reduction, ≥ 50% to < 75% reduction, > 0% to < 50% reduction, no change or any increase.	Baseline to Week 52
Absolute and percent change from baseline in daily maintenance OCS dose	Absolute and percent change from baseline in daily maintenance OCS dose at Week 28. Absolute change from baseline is defined as (final dose-baseline dose). Percent change from baseline is defined as {(final OCS dose-baseline OCS)/baseline OCS}*100.	Baseline to Week 28
Absolute and percent change from baseline in daily maintenance OCS dose	Absolute and percent change from baseline in daily maintenance OCS dose at Week 52. Absolute change from baseline is defined as (final dose-baseline dose). Percent change from baseline is defined as {(final OCS dose-baseline OCS)/baseline OCS}*100.	Baseline to Week 52
Change from baseline in post-bronchodilator (post-BD) FEV1	Change from baseline in post-bronchodilator (post-BD) FEV1 at Week 28. FEV1 is defined as as the volume of air exhaled from the lungs in the first second of a forced expiration.	Baseline to Week 28
Change from baseline in post-bronchodilator (post-BD) FEV1	Change from baseline in post-bronchodilator (post-BD) FEV1 at Week 52. FEV1 is defined as as the volume of air exhaled from the lungs in the first second of a forced expiration.	Baseline to Week 52
Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score	Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) at Week 28. The ACQ-6 captures asthma symptoms and short-acting β2 agonists use via subject-report. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses.	Baseline to Week 28
Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score	Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) at Week 52. The ACQ-6 captures asthma symptoms and short-acting β2 agonists use via subject-report. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses.	Baseline to Week 52
Change from baseline in standardised Asthma Quality of Life Questionnaire for 12 years and older (AQLQ[s]+12) total score	Change from baseline in standardised Asthma Quality of Life Questionnaire for 12 years and older (AQLQ[s]+12) total score at Week 28. The AQLQ[s]+12 is a questionnaire that measured the health-related quality of life experienced by asthma subjects. The total score is defined as the average of all 32 questions in the AQLQ[s]+12 questionnaire. AQLQ[s]+12 is 7 point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment). The total score is the mean of the responses.	Baseline to Week 28
Change from baseline in standardised Asthma Quality of Life Questionnaire for 12 years and older (AQLQ[s]+12) total score	Change from baseline in standardised Asthma Quality of Life Questionnaire for 12 years and older (AQLQ[s]+12) total score at Week 52. The AQLQ[s]+12 is a questionnaire that measured the health-related quality of life experienced by asthma subjects. The total score is defined as the average of all 32 questions in the AQLQ[s]+12 questionnaire. AQLQ[s]+12 is 7 point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment). The total score is the mean of the responses.	Baseline to Week 52
Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score	Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score at Week 28. The SGRQ is a questionnaire that measures health status of participants with airway obstruction diseases. The total score is expressed as a percentage of overall impairment, where 100 represents the worst possible health status and 0 indicates the best possible health status.	Baseline to Week 28
Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score	Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score at Week 52. The SGRQ is a questionnaire that measures health status of participants with airway obstruction diseases. The total score is expressed as a percentage of overall impairment, where 100 represents the worst possible health status and 0 indicates the best possible health status.	Baseline to Week 52

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2022
• Primary Completion (Estimated): September 12, 2024
• Study Completion (Estimated): September 12, 2024

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: March 9, 2022
• First Posted (Actual): March 10, 2022

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Asthma; Severe Asthma; Oral Corticosteroids
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: D5180C00037; 2021-005457-85 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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 request 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.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of the timelines, please rerefer to the disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No