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: Completed
• 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): 305
• 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
  • 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 Juan Bautista, Argentina, 1888
    • Research Site
  • San Miguel de Tucumán, Argentina, 4000
    • Research Site
• Belgium
  • Brussels (Woluwé-St-Lambert), Belgium, 1200
    • Research Site
  • Erpent, Belgium, 5101
    • Research Site
  • Ghent, 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, 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, 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
  • Jūrmala, Latvia, LV-2015
    • Research Site
  • Riga, Latvia, LV1002
    • Research Site
  • Riga, Latvia, LV1010
    • Research Site
  • Riga, Latvia, LV-1011
    • Research Site
  • Valmiera, Latvia, LV-4201
    • Research Site
• Mexico
  • Chihuahua City, Mexico, 31200
    • Research Site
  • Chihuahua City, 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
  • Gdansk, Poland, 80-952
    • Research Site
  • Krakow, Poland, 31-011
    • Research Site
  • Lodz, Poland, 92-213
    • 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
• Spain
  • Badalona, Spain, 08916
    • Research Site
  • Barcelona, Spain, 8035
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Oviedo, Spain, 33011
    • Research Site
  • Santa Cruz de Tenerife, Spain, 38010
    • Research Site
  • Santander, Spain, 39008
    • Research Site
  • Seville, Spain, 41009
    • Research Site
• United Kingdom
  • Belfast, United Kingdom, BT97AB
    • 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
    • The 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 the Participants Who Discontinued OCS Without Loss of Asthma Control at Week 28 and Week 52	The proportion (expressed as a percentage) of participants who discontinued OCS without loss of asthma control is presented. Loss of asthma control was defined as asthma worsening or exacerbation. Asthma worsening was defined by an increase of Asthma Control Questionnaire 6 (ACQ-6) score ≥0.5 from baseline. Asthma exacerbation was defined by worsening of asthma symptoms that led to temporary bolus/burst of systemic corticosteroids (SCS; or a temporary increase in stable OCS background dose) for at least 3 consecutive days (a single depo-injectable dose of corticosteroids being considered equivalent to a 3-day bolus/burst of SCS), and/or an emergency room (ER) or urgent care visit requiring SCS, and/or inpatient hospitalisation, both due to asthma.	Week 28 and Week 52
Proportion of the Participants Who Reduced Daily Prescribed Maintenance OCS Dose to ≤5 mg/Day Without Loss of Asthma Control at Week 28 and Week 52	The proportion (expressed as a percentage) of the participants who reduced daily prescribed maintenance OCS dose to ≤5 mg/day without loss of asthma control at Week 28 and Week 52 is presented.	Week 28 and Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual Asthma Exacerbation Rate (AAER) Over Week 28 and Over Week 52	The AAER over Week 28 and over Week 52 is presented. The AAER was calculated as the total number of asthma exacerbations over the period (Week 28/52) divided by the total time at risk for the period (Week 28 or Week 52).	Week 28 and Week 52
Rate of Asthma Exacerbation Associated With Hospitalisation or ER Visit Over 28 Weeks and Over 52 Weeks	The AAER for exacerbations associated with hospitalisation or ER visit over 28 weeks and over 52 weeks is presented. The AAER was calculated as the total number of asthma exacerbations over the period (Week 28/52) divided by the total time at risk for the period (Week 28 or Week 52).	Week 28 and Week 52
Rate of Asthma Exacerbation Associated With Hospitalisation Over 28 Weeks and Over 52 Weeks	The AAER for exacerbations associated with hospitalisation over 28 weeks and over 52 weeks are presented. The AAER was calculated as the total number of asthma exacerbations over the period (Week 28/52) divided by the total time at risk for the period (Week 28 or Week 52).	Week 28 and Week 52
Proportion of the Participants Who Did Not Experience an Exacerbation Over 28 Weeks and Over 52 Weeks	The proportion (expressed as a percentage) of participants who completed 28 or 52 weeks of treatment and did not experience an exacerbation over 28 weeks and over 52 weeks is presented.	Week 28 and Week 52
Proportion of the Participants Who Did Not Experience an Exacerbation Associated With Hospitalisation or ER Visit Over 28 Weeks and Over 52 Weeks	The proportion (expressed as a percentage) of participants who completed 28 or 52 weeks of treatment and did not experience an exacerbation associated with hospitalisation or ER visit over 28 weeks and over 52 weeks is presented.	Week 28 and Week 52
Proportion of the Participants Who Did Not Experience an Exacerbation Associated With Hospitalisation Over 28 Weeks and Over 52 Weeks	The proportion (expressed as a percentage) of participants who completed 28 or 52 weeks of treatment and did not experience an exacerbation associated with hospitalisation over 28 weeks and over 52 weeks is presented.	Week 28 and Week 52
Proportion of the Participants With ≥50% Reduction From Baseline in Daily Maintenance OCS Dose at Week 28 and Week 52	The proportion (expressed as a percentage) of participants with ≥50% reduction from baseline in daily maintenance OCS dose at Week 28 and Week 52 is presented. The baseline OCS dose is the prescribed OCS dose prior to first dose of investigational product (IP). The final daily OCS dose was defined as the last dose reported by participants with asthma stability verified (no change in OCS dose for at least 2 consecutive weeks).	Week 28 and Week 52
Categorised Percent Reduction From Baseline in the Daily Maintenance OCS Dose at Week 28 and Week 52	The categorised percent reduction from baseline in the daily maintenance OCS dose (categories: ≥90% to ≤100% reduction, ≥75% to <90% reduction, ≥50% to <75% reduction, >0% to <50% reduction, no change or any increase) at Week 28 and Week 52 is presented. The baseline OCS dose is the prescribed OCS dose prior to first dose of IP. The final daily OCS dose was defined as the last dose reported by participants with asthma stability verified (no change in OCS dose for at least 2 consecutive weeks).	Week 28 and Week 52
Absolute Change From Baseline in Daily Maintenance OCS Dose at Week 28 and Week 52	The absolute change from baseline in daily maintenance OCS dose at Week 28 and Week 52 is presented. The baseline OCS dose is the prescribed OCS dose prior to first dose of IP. The final daily OCS dose was defined as the last dose reported by participants with asthma stability verified (no change in OCS dose for at least 2 consecutive weeks).	Week 28 and Week 52
Percent Change From Baseline in Daily Maintenance OCS Dose at Week 28 and Week 52	The percent change from baseline in daily maintenance OCS dose at Week 28 and Week 52 is presented. The baseline OCS dose is the prescribed OCS dose prior to first dose of IP. The final daily OCS dose was defined as the last dose reported by participants with asthma stability verified (no change in OCS dose for at least 2 consecutive weeks).	Week 28 and Week 52
Change From Baseline in Post-bronchodilator FEV1 at Week 28 and Week 52	The change from baseline in post-bronchodilator FEV1 at Week 28 and Week 52 is presented. Baseline was defined as the last measurement at or prior first dose of IP. FEV1 = forced expiratory volume in 1 second	Week 28 and Week 52
Change From Baseline in ACQ-6 at Week 28 and Week 52	The Asthma Control Questionnaire 6 (ACQ-6) is a 6-item questionnaire which includes the following questions: 1) Awakening at night by symptoms, 2) Limitations of normal daily activities, 3) Waking in the morning with symptoms, 4) Dyspnoea, 5) Wheeze, and 6) Daily rescue medication. Questions were scored from 0 (totally controlled) to 6 (severely uncontrolled) and the ACQ-6 score was computed as the unweighted mean of the responses to the 6 questions. Higher scores indicate poorer outcomes. The change from baseline in ACQ-6 at Week 28 and Week 52 is presented.	Week 28 and Week 52
Change From Baseline in Standardised AQLQ(s)+12 Total Score at Week 28 and Week 52	The Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ[S]+12) is a questionnaire that measures the health-related quality of life experienced by asthma participants. Questions were scored from 7 (no impairment) to 1 (severe impairment). The overall score is calculated as the mean response to all questions. Higher scores indicate better outcomes. The change from baseline in standardised AQLQ(S)+12 total score at Week 28 and Week 52 is presented.	Week 28 and Week 52
Change From Baseline in SGRQ Total Score at Week 28 and Week 52	The St. George's Respiratory Questionnaire (SGRQ) is a 50-item instrument developed to measure the health status of participants with airway obstruction diseases. The total score indicates the impact of disease on overall health status. The total score ranges for the SGRQ are 0-100, with higher scores indicating worse health status. The change from baseline in SGRQ total score at Week 28 and Week 52 is presented.	Week 28 and Week 52

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Jackson DJ, Lugogo NL, Gurnell M, Heaney LG, Korn S, Brusselle G, Chanez P, Del Olmo R, Llanos JP, Keeling N, Salapa K, Cook B, Parulekar AD, Kostikas K, Fogel R, Martin N, Chandarana SN. Oral corticosteroid reduction and discontinuation in adults with corticosteroid-dependent, severe, uncontrolled asthma treated with tezepelumab (WAYFINDER): a multicentre, single-arm, phase 3b trial. Lancet Respir Med. 2025 Nov 26:S2213-2600(25)00359-5. doi: 10.1016/S2213-2600(25)00359-5. Online ahead of print.

Helpful Links

• Redacted CSP
• Redacted CSR Synopsis
• Redacted SAP

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2022
• Primary Completion (Actual): September 9, 2024
• Study Completion (Actual): September 9, 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): December 11, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Asthma; Severe Asthma; Oral Corticosteroids
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma; tezepelumab
• 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