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.
Brief Title
Study to Evaluate Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adult Patients With Severe Asthma
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Asthma
Eligibility 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 exclusion criteria per protocol apply.
* 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.
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Keywords
Asthma
Severe Asthma
Oral Corticosteroids
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
80 Years
Minimum Age
18 Years
NCT Id
NCT05274815
Org Class
Industry
Org Full Name
AstraZeneca
Org Study Id
D5180C00037
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome Description
Proportion of participants who discontinued OCS without loss of asthma control at Week 28.
Outcome Measure
Proportion of participants who discontinued OCS without loss of asthma control
Outcome Time Frame
At Week 28
Outcome Description
Proportion of participants who discontinued OCS without loss of asthma control at Week 52.
Outcome Measure
Proportion of participants who discontinued OCS without loss of asthma control
Outcome Time Frame
At Week 52
Outcome Description
Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control at Week 28.
Outcome Measure
Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control
Outcome Time Frame
At Week 28
Outcome Description
Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control at Week 52.
Outcome Measure
Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control
Outcome Time Frame
At Week 52
Secondary Ids
Secondary Id
2021-005457-85
Secondary Outcomes
Outcome Description
The annualised asthma exacerbation rate is based on exacerbations reported by investigator in eCRF over 28 weeks.
Outcome Time Frame
Baseline to Week 28
Outcome Measure
The Annualised Asthma Exacerbation Rate
Outcome Description
The annualised asthma exacerbation rate is based on exacerbations reported by investigator in eCRF over 52 weeks.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
The Annualised Asthma Exacerbation Rate
Outcome Description
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.
Outcome Time Frame
Baseline to Week 28
Outcome Measure
Rate of asthma exacerbation associated with hospitalisation or emergency room (ER)
Outcome Description
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.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Rate of asthma exacerbation associated with hospitalisation or emergency room (ER)
Outcome Description
Rate of asthma exacerbation is based on exacerbations reported by the investigator in eCRF that are associated with a hospitalization over 28 weeks.
Outcome Time Frame
Baseline to Week 28
Outcome Measure
Rate of asthma exacerbation associated with hospitalisation
Outcome Description
Rate of asthma exacerbation is based on exacerbations reported by the investigator in eCRF that are associated with a hospitalization over 52 weeks.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Rate of asthma exacerbation associated with hospitalisation
Outcome Description
Proportion of participants who did not experience an exacerbation over 28 weeks.
Outcome Time Frame
Baseline to Week 28
Outcome Measure
Proportion of participants who did not experience an exacerbation
Outcome Description
Proportion of participants who did not experience an exacerbation over 52 weeks.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Proportion of participants who did not experience an exacerbation
Outcome Description
Proportion of participants who did not experience an exacerbation associated with hospitalization or ER visit over 28 weeks.
Outcome Time Frame
Baseline to Week 28
Outcome Measure
Proportion of participants who did not experience an exacerbation associated with hospitalisation or ER visit
Outcome Description
Proportion of participants who did not experience an exacerbation associated with hospitalization or ER visit over 52 weeks.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Proportion of participants who did not experience an exacerbation associated with hospitalisation or ER visit
Outcome Description
Proportion of participants who did not experience an exacerbation associated with hospitalization over 28 weeks.
Outcome Time Frame
Baseline to Week 28
Outcome Measure
Proportion of participants who did not experience an exacerbation associated with hospitalisation
Outcome Description
Proportion of participants who did not experience an exacerbation associated with hospitalization over 52 weeks.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Proportion of participants who did not experience an exacerbation associated with hospitalisation
Outcome Description
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.
Outcome Time Frame
Baseline to Week 28
Outcome Measure
Proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose
Outcome Description
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.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose
Outcome Description
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.
Outcome Time Frame
Baseline to Week 28
Outcome Measure
Categorised percent reduction from baseline in the daily maintenance OCS dose
Outcome Description
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.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Categorised percent reduction from baseline in the daily maintenance OCS dose
Outcome Description
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.
Outcome Time Frame
Baseline to Week 28
Outcome Measure
Absolute and percent change from baseline in daily maintenance OCS dose
Outcome Description
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.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Absolute and percent change from baseline in daily maintenance OCS dose
Outcome Description
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.
Outcome Time Frame
Baseline to Week 28
Outcome Measure
Change from baseline in post-bronchodilator (post-BD) FEV1
Outcome Description
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.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Change from baseline in post-bronchodilator (post-BD) FEV1
Outcome Description
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.
Outcome Time Frame
Baseline to Week 28
Outcome Measure
Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score
Outcome Description
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.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score
Outcome Description
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.
Outcome Time Frame
Baseline to Week 28
Outcome Measure
Change from baseline in standardised Asthma Quality of Life Questionnaire for 12 years and older (AQLQ[s]+12) total score
Outcome Description
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.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Change from baseline in standardised Asthma Quality of Life Questionnaire for 12 years and older (AQLQ[s]+12) total score
Outcome Description
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.
Outcome Time Frame
Baseline to Week 28
Outcome Measure
Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score
Outcome Description
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.
Outcome Time Frame
Baseline to Week 52
Outcome Measure
Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
80
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Golda Hudes
Investigator Email
ghudes@montefiore.org
Investigator Phone
646-229-9509