Trial Outcomes & Findings for Tezepelumab Efficacy and Safety in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma (NCT NCT05398263)

The study was conducted at 64 centres in 12 countries. Between 9AUG2022 and 29NOV2024, 250 subjects were screened; 125 were randomized and treated, and 125 were not randomized mainly due to screen failures. Four participants (1 tezepelumab, 2 placebo, 1 screen failure) from one site were excluded for quality issues, so 122 randomized participants were analysed. The sponsor terminated the study early due to recruitment challenges.

Assignment was done by Interactive Voice/Web Response System (IVRS/IWRS). Subjects were randomized in 2:1 ratio for tezepelumab or placebo. Randomization was stratified by region and eosinophil count at Visit 1 (\< 150 cells/μL, 150-\< 300 cells/μL, ≥ 300 cells/μL).

Tezepelumab Efficacy and Safety in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma

Proportion of subjects by 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.

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 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.

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%.

The annualized exacerbation rate is based on exacerbations reported by the investigator in the eCRF over 28 weeks.

Time to first asthma exacerbation, presented as proportion of subjects with at least one asthma exacerbation as reported by the investigator in the eCRF

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.

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 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 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.

Change from baseline in fractional exhaled nitric oxide (FeNO) at Week 28.

Change from baseline in blood eosinophil counts at Week 28.

Change from baseline in total serum IgE at 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).

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.