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

Asthma Clinical Trial

— WAYFINDER  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05274815
• Other study ID #: D5180C00037
• Secondary ID: 2021-005457-85
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 17, 2022
• Est. completion date: September 12, 2024

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 306
• Est. completion date: September 12, 2024
• Est. primary completion date: September 12, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• Tezepelumab
Tezepelumab subcutaneous injection

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Florencio Varela
Argentina	Research Site	Mendoza
Argentina	Research Site	Monte Grande
Argentina	Research Site	Pilar
Argentina	Research Site	Quilmes
Argentina	Research Site	Ranelagh
Argentina	Research Site	Rosario
Argentina	Research Site	San Fernando
Argentina	Research Site	San Miguel de Tucuman
Belgium	Research Site	Brussels (Woluwé-St-Lambert)
Belgium	Research Site	Erpent
Belgium	Research Site	Gent
Belgium	Research Site	Liège
Bulgaria	Research Site	Haskovo
Bulgaria	Research Site	Razgrad
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Velika Tarnovo
France	Research Site	Antony
France	Research Site	Bordeaux
France	Research Site	Brest Cedex
France	Research Site	Lyon
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Nantes
France	Research Site	Nice
Germany	Research Site	Berlin
Germany	Research Site	Darmstadt
Germany	Research Site	Fürstenwalde/Spree
Germany	Research Site	Mainz
Germany	Research Site	Reinfeld (Holstein)
Latvia	Research Site	Daugavpils
Latvia	Research Site	Daugavpils
Latvia	Research Site	Jurmala
Latvia	Research Site	Kyiv
Latvia	Research Site	Riga
Latvia	Research Site	Riga
Latvia	Research Site	Valmiera
Mexico	Research Site	Chihuahua
Mexico	Research Site	Chihuahua
Mexico	Research Site	Guadalajara
Mexico	Research Site	Monterrey
Poland	Research Site	Bychawa
Poland	Research Site	Chmielnik
Poland	Research Site	Gdansk
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Ostrowiec Swietokrzyski
Poland	Research Site	Sosnowiec
Poland	Research Site	Wroclaw
Poland	Research Site	Wroclaw
Poland	Research Site	Wroclaw
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Oviedo
Spain	Research Site	Santander
Spain	Research Site	Sevilla
Spain	Research Site	Tenerife
United Kingdom	Research Site	Belfast
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Le3 9qp
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Portsmouth
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Bronx	New York
United States	Research Site	DuBois	Pennsylvania
United States	Research Site	Loxahatchee Groves	Florida
United States	Research Site	Newark	Delaware
United States	Research Site	Newport Beach	California
United States	Research Site	Toms River	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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 ß2 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
Secondary	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 ß2 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
Secondary	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
Secondary	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
Secondary	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
Secondary	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