Tezepelumab Efficacy and Safety in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma
- Registration Number
- NCT05398263
- Lead Sponsor
- AstraZeneca
- Brief Summary
A Randomised, Double-Blind, Parallel-Group, Placebo-Controlled 28-week Phase 3 Efficacy and Safety Study of Tezepelumab in Reducing Oral Corticosteroid Use in Adults with Oral Corticosteroid Dependent Asthma
- Detailed Description
This is a multicentre, randomised, double-blind, placebo controlled, parallel group study designed to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma treated with maintenance OCS in combination with high dose inhaled corticosteroids (ICS) and long-acting β2 agonists (LABA), with or without other asthma controller therapies. Approximately 207 subjects will be randomized globally. Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection using the accessorized pre-filled syringe (APFS), over a 28-week treatment period. The study also includes a post-treatment follow-up period of 12 weeks.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 125
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tezepelumab Tezepelumab Tezepelumab subcutaneous injection, in an accessorised pre-filled syringe. Placebo Placebo Placebo subcutaneous injection, in an accessorised pre-filled syringe.
- Primary Outcome Measures
Name Time Method Categorised percent reduction from baseline in the daily maintenance OCS dose at Week 28 whilst maintaining asthma control. Baseline to Week 28 Categorised percent reduction from baseline at Week 28. Percent change from baseline is defined as {final dose-baseline dose)/baseline dose}\*100%, and the categories of percent change from baseline in daily OCS dose are defined as: ≥90% to ≤100% reduction, ≥75% to \<90% reduction, ≥50% to \<75% reduction, \>0% to \<50% reduction, and, no change or any increase.
- Secondary Outcome Measures
Name Time Method Proportion of subjects with 100% reduction from baseline in daily OCS dose at Week 28 Baseline to Week 28 Proportion of subjects with 100% reduction from baseline in daily OCS dose at Week 28. Percent change from baseline is defined as {(final dose-baseline dose)/baseline dose}\*100%.
Proportion of subjects with daily OCS dose ≤5 mg at Week 28 Week 28 Proportion of subjects with daily OCS dose ≤5 mg at Week 28.
Change from baseline in weekly mean home peak expiratory flow (PEF) (morning and evening) at Week 28 Baseline to Week 28 Change from baseline in weekly mean morning and evening peak expiratory flow (PEF) as compared to placebo at Week 28. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Each timepoint is calculated as weekly.
Change from baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(s)+12) total score at Week 28 Baseline to Week 28 Change from baseline in AQLQ(S)+12 as compared to placebo at Week 28. The AQLQ(S)+12 is a questionnaire that measures 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 a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment).
Change from baseline in fractional exhaled nitric oxide (FeNO) at Week 28 Baseline to Week 28 Change from baseline in fractional exhaled nitric oxide (FeNO) at Week 28.
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Score at Week 28 Baseline to Week 28 Change from baseline in SGRQ as compared to placebo at Week 28. The questionnaire is divided into 2 parts: part 1 consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status.
Immunogenicity: Incidence of anti-drug antibodies (ADA) at Week 0, 12, 28, and 40 Baseline to Week 40 Immunogenicity samples are collected at baseline and at Week 12 prior to study intervention administration, at Week 28 (End of Treatment visit) and at Week 40 (Follow-up visit). Persistently positive is defined as positive at \>=2 post baseline assessments (with \>=16 weeks between the first and the last positive) or positive at last post baseline assessment. Transiently positive is defined as having at least one post baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Treatment boosted ADA defined as baseline positive ADA that was boosted to a 4 fold or higher level following treatment. Treatment emergent ADA defined as sum of treatment induced ADA and treatment boosted ADA.
Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) at Week 28 Baseline to Week 28 Change from baseline in pre-BD FEV1 at Week 28. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration.
Proportion of subjects with ≥50% reduction from baseline in daily OCS dose at Week 28 Baseline to Week 28 Proportion of subjects with ≥50% reduction from baseline in daily OCS dose at Week 28. Percent change from baseline is defined as {(final dose-baseline dose)/baseline dose}\*100%.
Annualised asthma exacerbation rate (AAER) over 28 weeks Baseline to Week 28 The annualized exacerbation rate is based on exacerbations reported by the investigator in the eCRF over 28 weeks.
Time to first asthma exacerbation Baseline to Week 28 Time to first asthma exacerbation.
Change from baseline in peripheral blood eosinophils at Week 28 Baseline to Week 28 Change from baseline in blood eosinophil counts at Week 28.
Change from baseline in total serum immunoglobulin E (IgE) at Week 28 Baseline to Week 28 Change from baseline in total serum IgE at Week 28.
PK: Serum trough concentrations at Week 0, 12 and 28 Baseline, Week 12 and Week 28 Pharmacokinetics samples are collected at baseline and at Week 12 prior to study intervention administration, and at Week 28 (End of Treatment visit).
Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score at Week 28 Baseline to Week 28 Change from baseline in ACQ-6 as compared to placebo at Week 28. The ACQ-6 captures asthma symptoms and short-acting β2-agonist 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.
Trial Locations
- Locations (1)
Research Site
🇹🇷Izmir, Turkey