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

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)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05274815

Acronym

WAYFINDER

Enrollment

305

Registered

2022-03-10

Start date

2022-05-17

Completion date

2024-09-09

Last updated

2025-12-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

Asthma, Severe Asthma, Oral Corticosteroids

Brief summary

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.

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.

Interventions

BIOLOGICALTezepelumab

Tezepelumab subcutaneous injection

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Open label

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Inclusion criteria

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

Design outcomes

Primary

Measure	Time frame	Description
Proportion of the Participants Who Discontinued OCS Without Loss of Asthma Control at Week 28 and Week 52	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.
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	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.

Secondary

Measure	Time frame	Description
Rate of Asthma Exacerbation Associated With Hospitalisation or ER Visit Over 28 Weeks and Over 52 Weeks	Week 28 and Week 52	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).
Rate of Asthma Exacerbation Associated With Hospitalisation Over 28 Weeks and Over 52 Weeks	Week 28 and Week 52	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).
Proportion of the Participants Who Did Not Experience an Exacerbation Over 28 Weeks and Over 52 Weeks	Week 28 and Week 52	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.
Proportion of the Participants Who Did Not Experience an Exacerbation Associated With Hospitalisation or ER Visit Over 28 Weeks and Over 52 Weeks	Week 28 and Week 52	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.
Proportion of the Participants With ≥50% Reduction From Baseline in Daily Maintenance OCS Dose at Week 28 and Week 52	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).
Categorised Percent Reduction From Baseline in the Daily Maintenance OCS Dose at Week 28 and Week 52	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).
Proportion of the Participants Who Did Not Experience an Exacerbation Associated With Hospitalisation Over 28 Weeks and Over 52 Weeks	Week 28 and Week 52	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.
Percent Change From Baseline in Daily Maintenance OCS Dose at Week 28 and Week 52	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).
Change From Baseline in Post-bronchodilator FEV1 at Week 28 and Week 52	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
Change From Baseline in ACQ-6 at Week 28 and Week 52	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.
Change From Baseline in Standardised AQLQ(s)+12 Total Score at Week 28 and Week 52	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.
Change From Baseline in SGRQ Total Score at Week 28 and Week 52	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.
Absolute Change From Baseline in Daily Maintenance OCS Dose at Week 28 and Week 52	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).
Annual Asthma Exacerbation Rate (AAER) Over Week 28 and Over Week 52	Week 28 and 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).

Countries

Argentina, Belgium, Bulgaria, France, Germany, Latvia, Mexico, Poland, Spain, United Kingdom, United States

Participant flow

Recruitment details

A total of 305 participants were enrolled from 68 study sites across 11 countries, including sites in Argentina, Belgium, Bulgaria, France, Germany, Latvia, Mexico, Poland, Spain, UK, and USA.

Pre-assignment details

Of the 305 participants that initiated treatment with tezepelumab, 7 were excluded from the efficacy and safety summary due to potential data fraud. Therefore, only 298 participants were included in the summaries.

Participants by arm

Arm	Count
Tezepelumab Tezepelumab 210 mg was administered SC Q4W for a total of 13 doses. Induction phase (Week 0 to 4): Participants received tezepelumab treatment at Visit 2/Week 0 (baseline) and had to remain stable on their baseline OCS dose during this phase. OCS reduction and maintenance phase (Week 4 to 52): Initial OCS tapering was guided by an algorithm based on baseline OCS dose until the lowest stable OCS dose (OCS discontinued or no further OCS reduction possible) was reached or until Week 48; dosages were reduced in 2.5- to 5-mg increments weekly, every 2 weeks, or Q4W OCS dose.	298
Total	298

Arm

Count

Tezepelumab

Tezepelumab 210 mg was administered SC Q4W for a total of 13 doses. Induction phase (Week 0 to 4): Participants received tezepelumab treatment at Visit 2/Week 0 (baseline) and had to remain stable on their baseline OCS dose during this phase. OCS reduction and maintenance phase (Week 4 to 52): Initial OCS tapering was guided by an algorithm based on baseline OCS dose until the lowest stable OCS dose (OCS discontinued or no further OCS reduction possible) was reached or until Week 48; dosages were reduced in 2.5- to 5-mg increments weekly, every 2 weeks, or Q4W OCS dose.

298

Total

298

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Death	2
Overall Study	Lost to Follow-up	4
Overall Study	Withdrawal by Subject	11
Overall Study	Withdrawn due to participant's decision not to continue for personal and family reasons	1
Overall Study	Withdrawn from study due to investigator's decision	1
Overall Study	Withdrawn from study due to participant's decision to withdraw	1
Overall Study	Withdrawn from study due to randomization into closed cohort by mistake	1
Overall Study	Withdrawn from study due to severe non-compliance with the protocol	1
Overall Study	Withdrawn from study due to subject decision	1
Overall Study	Withdrawn from study due to the participant stopped visit; agreed to a telephone contact at Week 52	1

Baseline characteristics

Characteristic	Tezepelumab
Age, Continuous	54.4 Years STANDARD_DEVIATION 12
Age, Customized >=18 to <65 years	231 Participants
Age, Customized >=65 years	67 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants
Race/Ethnicity, Customized Hispanic or Latino	123 Participants
Race/Ethnicity, Customized Missing	18 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	157 Participants
Race/Ethnicity, Customized Not reported	18 Participants
Race/Ethnicity, Customized Other	15 Participants
Race/Ethnicity, Customized White	258 Participants
Region of Enrollment Argentina	80 Participants
Region of Enrollment Belgium	13 Participants
Region of Enrollment Bulgaria	36 Participants
Region of Enrollment France	18 Participants
Region of Enrollment Germany	22 Participants
Region of Enrollment Latvia	16 Participants
Region of Enrollment Mexico	41 Participants
Region of Enrollment Poland	40 Participants
Region of Enrollment Spain	8 Participants
Region of Enrollment United Kingdom	12 Participants
Region of Enrollment United States	12 Participants
Sex: Female, Male Female	206 Participants
Sex: Female, Male Male	92 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	2 / 298
other Total, other adverse events	4 / 298
serious Total, serious adverse events	28 / 298

Outcome results

Primary

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.