STEP: Phase IIIb Study of Benralizumab to Step-down Maintenance Therapy in Patients With Severe Eosinophilic Asthma
NCT Number: NCT06465485
Acronym: STEP
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Severe Eosinophilic Asthma
Interventions: DRUG: Benralizumab
Sponsor: AstraZeneca
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 200
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-02-28
Completion Date: 2026-07-31
Locations: Research Site, Beijing, 100020, China|Research Site, Beijing, 100029, China|Research Site, Beijing, 100191, China|Research Site, Chengdu, 610014, China|Research Site, Chengdu, 610072, China|Research Site, Guangzhou, 510280, China|Research Site, Guangzhou, 510630, China|Research Site, Hangzhou, 310009, China|Research Site, Hohhot, 10050, China|Research Site, Huzhou, 313003, China|Research Site, Jinan, 250012, China|Research Site, Jinan, 250014, China|Research Site, Lanzhou, 730000, China|Research Site, Lanzhou, 730030, China|Research Site, Nanjing, 211100, China|Research Site, Nanning, 530021, China|Research Site, Ningbo, 315010, China|Research Site, Shanghai, 200065, China|Research Site, Shanghai, 200080, China|Research Site, Shenzhen, 518001, China|Research Site, Shenzhen, 518036, China|Research Site, Shenzhen, 518039, China|Research Site, Shenzhen, 518101, China|Research Site, Shijiazhuang, 054001, China|Research Site, Shijiazhuang, 50051, China|Research Site, Suzhou, 215004, China|Research Site, Suzhou, 215006, China|Research Site, Taiyuan, 030001, China|Research Site, Tangshan, 63000, China|Research Site, Wenzhou, 325000, China|Research Site, Wuhu, 241000, China|Research Site, Xi'an, 710006, China|Research Site, Xinxiang, 453100, China|Research Site, Yangzhou, 225001, China|Research Site, Zhangzhou, 363099, China|Research Site, Zhengzhou, 450007, China

Summary:
This is a prospective, multi-center, single-arm Phase 3b study designed to evaluate the potential benefit to patients if benralizumab treatment could enable reduction in asthma maintenance controllers while allowing patients to maintain asthma control in Chinese patients.

Primary Outcome Measures: To assess the potential for benralizumab treated patients to reduce their standard of care asthma controller regimen, Main outcomes: Proportion of patients with at least one controller medication category reduction at end of reduction phase

* discontinuation of LTRA, or
* discontinuation of LAMA, or
* discontinuation of theophylline, or
* getting to MD ICS/LABA, or
* getting to LD ICS/LABA

Supportive outcomes:

* Proportion of patients with individual category reduction at end of reduction phase
* Proportion of patients with ≥2 category reductions in controller medication
* In sub-group of patients who meet reduction criteria
* proportion of patients with at least one controller medication category reduction,
* proportion of patients with individual category reduction
* proportion of patients with ≥2 reductions in controller medication at end of reduction phase, within 40 weeks after the first administration
Secondary Outcome Measures: To assess standard asthma efficacy measures for benralizumab treated patients when reducing their standard of care asthma controller regimen for pulmonary function measured by pre-BD FEV1 in litres, Change in pre-BD FEV1 measured in litres from beginning of reduction phase to end of reduction phase, From 16~40 weeks|To assess standard asthma efficacy measures for benralizumab treated patients when reducing their standard of care asthma controller regimen for asthma symptoms control measured by ACQ-IA Score, * Change in measured by ACQ-IA score from beginning of reduction phase to end of reduction phase
* Measured by Proportion of patients with no deterioration (defined as ACQ-IA score change \<0.5 score since last visit) during reduction phase, From 16~40 weeks|To assess if reductions in background therapies achieved at end of reduction phase are maintained until end of maintenance phase, Measured by Proportion of patients at the end of the maintenance phase who use the same background therapy that they achieved at the end of the reduction phase, from 40-56 weeks|To assess if reductions in background therapies achieved at end of reduction phase are maintained until end of maintenance phase, Change in measured by ACQ-IA score from the end of the reduction phase to the end of the maintenance phase, from 40-56 weeks|To assess if reductions in background therapies achieved at end of reduction phase are maintained until end of maintenance phase, Change in measured by FEV1 in litres from the end of the reduction phase to the end of the maintenance phase, from 40-56 weeks|To assess standard asthma efficacy measures for benralizumab treated patients at induction phase, Change in measured by FEV1 in litres from beginning of induction phase to end of induction phase, within 0-16 weeks after first administration|To assess standard asthma efficacy measures for benralizumab treated patients at induction phase, * Change in measured by ACQ-IA score from beginning of induction phase to end of induction phase
* Measured by Proportion of patients achieving ACQ-IA score MCID improvement (defined as change in ACQ-IA score ≤-0.5 compared to beginning of induction phase) at end of induction phase, within 0-16 weeks after first administration|To assess overall asthma exacerbation rate during the study of severe eosinophilic asthma patients treated with benralizumab, * Annualized asthma exacerbation rate during the study (from first dose to EOT) and 1-year baseline period
* Change in annualized asthma exacerbation rate during study phase vs. 1-year baseline period

Annualized asthma exacerbation rate Defined as Number of exacerbations×365.25/(Follow-Up Date-First Benralizumab dose date+1), within 56 weeks after first administration|To assess biomarkers of severe eosinophilic asthma patients treated with benralizumab, Baseline and follow-up visits, and change from baseline:

Blood EOS measured as cells per litre, from -1 week to 56 week|To assess biomarkers of severe eosinophilic asthma patients treated with benralizumab, Baseline and follow-up visits, and change from baseline:· FeNO measured as parts per billion, from -1 week to 56 week|To assess the safety and tolerability of benralizumab.Number of participants with treatment-related adverse events as asessed by CTCAEV5.0., The number of patients experiencing any Treatment related AEs/SAEs, from -1 week to 60 week