Clinical trial NCT05274815: Study to Evaluate Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adult Patients With Severe Asthma
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Severe Asthma
Oral Corticosteroids
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-03-10
Enrollment: 306
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Proportion of participants who discontinued OCS without loss of asthma control
timeFrame: At Week 28
measure: Proportion of participants who discontinued OCS without loss of asthma control
timeFrame: At Week 52
measure: Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control
timeFrame: At Week 28
measure: Proportion of participants who reduced daily prescribed maintenance OCS dose to ≤ 5 mg/day without loss of asthma control
timeFrame: At Week 52
Secondary outcomes:
measure: The Annualised Asthma Exacerbation Rate
timeFrame: Baseline to Week 28
measure: The Annualised Asthma Exacerbation Rate
timeFrame: Baseline to Week 52
measure: Rate of asthma exacerbation associated with hospitalisation or emergency room (ER)
timeFrame: Baseline to Week 28
measure: Rate of asthma exacerbation associated with hospitalisation or emergency room (ER)
timeFrame: Baseline to Week 52
measure: Rate of asthma exacerbation associated with hospitalisation
timeFrame: Baseline to Week 28
measure: Rate of asthma exacerbation associated with hospitalisation
timeFrame: Baseline to Week 52
measure: Proportion of participants who did not experience an exacerbation
timeFrame: Baseline to Week 28
measure: Proportion of participants who did not experience an exacerbation
timeFrame: Baseline to Week 52
measure: Proportion of participants who did not experience an exacerbation associated with hospitalisation or ER visit
timeFrame: Baseline to Week 28
measure: Proportion of participants who did not experience an exacerbation associated with hospitalisation or ER visit
timeFrame: Baseline to Week 52
measure: Proportion of participants who did not experience an exacerbation associated with hospitalisation
timeFrame: Baseline to Week 28
measure: Proportion of participants who did not experience an exacerbation associated with hospitalisation
timeFrame: Baseline to Week 52
measure: Proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose
timeFrame: Baseline to Week 28
measure: Proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose
timeFrame: Baseline to Week 52
measure: Categorised percent reduction from baseline in the daily maintenance OCS dose
timeFrame: Baseline to Week 28
measure: Categorised percent reduction from baseline in the daily maintenance OCS dose
timeFrame: Baseline to Week 52
measure: Absolute and percent change from baseline in daily maintenance OCS dose
timeFrame: Baseline to Week 28
measure: Absolute and percent change from baseline in daily maintenance OCS dose
timeFrame: Baseline to Week 52
measure: Change from baseline in post-bronchodilator (post-BD) FEV1
timeFrame: Baseline to Week 28
measure: Change from baseline in post-bronchodilator (post-BD) FEV1
timeFrame: Baseline to Week 52
measure: Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score
timeFrame: Baseline to Week 28
measure: Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score
timeFrame: Baseline to Week 52
measure: Change from baseline in standardised Asthma Quality of Life Questionnaire for 12 years and older (AQLQ[s]+12) total score
timeFrame: Baseline to Week 28
measure: Change from baseline in standardised Asthma Quality of Life Questionnaire for 12 years and older (AQLQ[s]+12) total score
timeFrame: Baseline to Week 52
measure: Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score
timeFrame: Baseline to Week 28
measure: Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score
timeFrame: Baseline to Week 52
Other outcomes:
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city: Nottingham
country: United Kingdom
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city: Portsmouth
country: United Kingdom
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Study officials:
References: