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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Asthma

Intervention / Treatment
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* Biological: Tezepelumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tezepelumab<br>Tezepelumab subcutaneous injection | Biological: Tezepelumab<br>* Tezepelumab subcutaneous injection<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Severe Asthma, Oral Corticosteroids