Trial Outcomes & Findings for A Study to Assess the Reduction of Daily Maintenance ICS/LABA Treatment Towards Anti-Inflammatory Reliever Treatment in Patients With Severe Eosinophilic Asthma Treated With Benralizumab (NCT NCT04159519)

Results Overview

Proportion of patients with non-missing Week 32 dose who reduced their Symbicort® maintenance dose at the end of the reduction period (Week 32) to: a) Medium-dose Symbicort® maintenance and reliever therapy (SMART), or b) Low-dose SMART, or c) Symbicort® anti-inflammatory reliever only.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

170 participants

Primary outcome timeframe

At Week 32

Results posted on

2025-01-09

Participant Flow

The study was conducted between 27 July 2020 and 31 January 2023.

Study began with Screening Visit (Visit 1), followed by 4-8 weeks of screening and run-in. Patients previously exposed to benralizumab and ICS/LABA maintenance treatment prior to study entry received a high dose of Symbicort. At week 0 (Visit 2), 168 patients who met inclusion and randomization criteria were selected to participate in study and received study intervention benralizumab. These patients were randomly assigned to either treatment reduction arm or the reference arm.

Participant milestones

Participant milestones
Measure	Treatment Reduction Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Overall Study STARTED	125	43
Overall Study COMPLETED	117	37
Overall Study NOT COMPLETED	8	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Reduction Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Overall Study Adverse Event	1	1
Overall Study Lack of Efficacy	1	0
Overall Study Discontinued from study	1	0
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	4	4

Baseline Characteristics

A Study to Assess the Reduction of Daily Maintenance ICS/LABA Treatment Towards Anti-Inflammatory Reliever Treatment in Patients With Severe Eosinophilic Asthma Treated With Benralizumab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Reduction n=125 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=43 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.	Total n=168 Participants Total of all reporting groups
Age, Continuous	58.1 Years STANDARD_DEVIATION 12.44 • n=5 Participants	56.5 Years STANDARD_DEVIATION 11.70 • n=7 Participants	57.7 Years STANDARD_DEVIATION 12.24 • n=5 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	20 Participants n=7 Participants	89 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	23 Participants n=7 Participants	79 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	91 Participants n=5 Participants	28 Participants n=7 Participants	119 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	26 Participants n=5 Participants	9 Participants n=7 Participants	35 Participants n=5 Participants
Race/Ethnicity, Customized White	95 Participants n=5 Participants	31 Participants n=7 Participants	126 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Missing	23 Participants n=5 Participants	9 Participants n=7 Participants	32 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Week 32

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study. Here, overall "number of participants analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

Proportion of patients with non-missing Week 32 dose who reduced their Symbicort® maintenance dose at the end of the reduction period (Week 32) to: a) Medium-dose Symbicort® maintenance and reliever therapy (SMART), or b) Low-dose SMART, or c) Symbicort® anti-inflammatory reliever only.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=119 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Proportion of Patients Who Reduced Their Symbicort® Maintenance Dose at the End of the Reduction Period Medium-dose SMART	0.151 Proportion of Participants Interval 0.0922 to 0.2285	—
Proportion of Patients Who Reduced Their Symbicort® Maintenance Dose at the End of the Reduction Period Low-dose SMART	0.168 Proportion of Participants Interval 0.1058 to 0.2476	—
Proportion of Patients Who Reduced Their Symbicort® Maintenance Dose at the End of the Reduction Period Symbicort® reliever-only dose	0.605 Proportion of Participants Interval 0.5113 to 0.6934	—

SECONDARY outcome

Timeframe: Week 0 (baseline) and at Week 32

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study. Here, overall "number of participants analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

Change from baseline in the ACQ-5 patient reported outcome. This instrument contains 5 asthma symptom questions, rated from 0 (total control) to 6 (severely uncontrolled). The ACQ-5 score is the mean of the responses. Mean scores ≤0.75 indicate well controlled, scores between \>0.75 and \<1.5 indicate partly controlled, ≥1.5 indicate not well controlled asthma, and individual changes of ≥0.5 are considered to be clinically meaningful. ACQ-5 deterioration is defined as at least a 0.5 unit increase in ACQ-5 score from baseline, and a decrease of at least 0.5 units from baseline indicates improved asthma control.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=112 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=38 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Change From Baseline in Asthma Control Questionnaire-5 Item (ACQ-5) Score at the End of the Reduction Period	0.1617 Score on a scale Standard Error 0.0393	0.0555 Score on a scale Standard Error 0.0677

SECONDARY outcome

Timeframe: Week 0 (baseline) and at Week 32

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study. Here, overall "number of participants analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

The AQLQ(S)+12 is a Patient-Reported Outcome (PRO) that measures the health-related quality of life experienced by asthma patients. The questionnaire comprises 4 separate domains (symptoms, activity limitations, emotional function, and environmental stimuli). Patients are asked to recall their experiences during the previous 2 weeks before each visit and to score each of the questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). Range of Total Score = 0 - 7 as it is an average of responses to the individual questions. High score = better quality of life, and low score = poor quality of life. Change of \>0.5 from baseline is considered a meaningful improvement in score.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=99 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=35 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Change From Baseline in Standardised Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) at the End of the Reduction Period	-0.0279 Score on a scale Standard Error 0.0559	0.0064 Score on a scale Standard Error 0.0950

SECONDARY outcome

Timeframe: At Week 32

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study.

The AQLQ(S)+12 is a PRO that measures the health-related quality of life experienced by asthma patients. The questionnaire comprises 4 separate domains (symptoms, activity limitations, emotional function, and environmental stimuli). Patients are asked to recall their experiences during the previous 2 weeks before each visit and to score each of the questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). AQLQ(S)+12 deterioration was defined as at least a 0.5 unit decrease in AQLQ(S)+12 total score from baseline. Patients with no deterioration include patients with improvement or no change.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=125 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=43 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Number of Patients With no Deterioration in AQLQ(S)+12 at the End of the Reduction Period Improvement	12 Participants	3 Participants
Number of Patients With no Deterioration in AQLQ(S)+12 at the End of the Reduction Period No change	73 Participants	28 Participants

SECONDARY outcome

Timeframe: At Week 32

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study.

Change from baseline in the ACQ-5 patient reported outcome. This instrument contains 5 asthma symptom questions, rated from 0 (total control) to 6 (severely uncontrolled). The ACQ-5 score is the mean of the responses. Mean scores ≤0.75 indicate well controlled, scores between \>0.75 and \<1.5 indicate partly controlled, ≥1.5 indicate not well controlled asthma, and individual changes of ≥0.5 are considered to be clinically meaningful. ACQ-5 deterioration is defined as at least a 0.5 units increase in ACQ-5 score from baseline, and a decrease of at least 0.5 units from baseline indicates improved asthma control.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=125 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=43 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Number of Patients With no Deterioration in ACQ-5 at the End of the Reduction Period Improvement	6 Participants	2 Participants
Number of Patients With no Deterioration in ACQ-5 at the End of the Reduction Period No change	87 Participants	28 Participants

SECONDARY outcome

Timeframe: At Week 0 (baseline), and at Weeks 8, 16, 24, 32, 40, and 48

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study. Here, overall "number of participants analyzed", and "number analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

The potential for benralizumab-treated patients to maintain lung function while stepping down Symbicort® maintenance treatment was assessed. The FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration, expressed in liters. Change from baseline pre-bronchodilator FEV1 calculated as post-baseline pre-bronchodilator FEV1 (L) minus baseline pre-bronchodilator FEV1 (L) for all post-baseline measurement points.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=125 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=43 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) During the Study Period Week 32	-0.0824 Liter Standard Error 0.0285	-0.0016 Liter Standard Error 0.0482
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) During the Study Period Week 40	-0.0953 Liter Standard Error 0.0280	0.0428 Liter Standard Error 0.0476
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) During the Study Period Week 48	-0.0889 Liter Standard Error 0.0272	0.0059 Liter Standard Error 0.0475
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) During the Study Period Week 8	0.0411 Liter Standard Error 0.0183	0.0549 Liter Standard Error 0.0315
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) During the Study Period Week 16	0.0299 Liter Standard Error 0.0215	0.0115 Liter Standard Error 0.0363
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) During the Study Period Week 24	-0.0536 Liter Standard Error 0.0317	0.0644 Liter Standard Error 0.0540

SECONDARY outcome

Timeframe: From Week 0 up to Week 48

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study.

Asthma exacerbation rate was assessed. An asthma exacerbation was defined as a worsening of asthma symptoms that led to any of the following: a) Temporary bolus/burst of systemic corticosteroids (≥3 consecutive days); b) Single depo-injectable dose of corticosteroids (equivalent to a 3-day bolus/burst); c) Visit to emergency room/urgent care (treatment \<24 hours) requiring systemic corticosteroids; d) Hospitalization (admission/evaluation ≥24 hours) due to asthma.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=125 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=43 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Annualised Asthma Exacerbation Rate During the Study Period	0.14 Events/Year Interval 0.09 to 0.23	0.14 Events/Year Interval 0.06 to 0.31

SECONDARY outcome

Timeframe: Reduction period (From Week 0 up to Week 32); maintenance period (From Week 32 up to Week 48); Study period (Week 0 up to end of maintenance period/ end of study)

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study. Here, overall "number of participants analyzed", and "number analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

The cumulative total daily ICS dose (maintenance +reliever) for: a) reduction period; b) maintenance period; c) study period was assessed.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=125 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=42 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Cumulative Total Daily Inhaled Corticosteroids (ICS) Dose, by Period Reduction period	115956.8 Microgram Standard Deviation 73223.93	312857.1 Microgram Standard Deviation 81251.22
Cumulative Total Daily Inhaled Corticosteroids (ICS) Dose, by Period Maintenance period	50984.3 Microgram Standard Deviation 51148.59	150400.0 Microgram Standard Deviation 42180.46
Cumulative Total Daily Inhaled Corticosteroids (ICS) Dose, by Period Study period	157560.0 Microgram Standard Deviation 114123.69	448933.3 Microgram Standard Deviation 131247.22

SECONDARY outcome

Timeframe: At Week 32

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study. Here, overall "number of participants analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

The mean total daily ICS dose (maintenance + reliever) during the 8 weeks prior to end of the reduction period was assessed.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=120 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=39 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Total Daily ICS Dose (Maintenance + Reliever) at the End of the Reduction Period	380.028 Microgram Standard Deviation 440.4995	1401.796 Microgram Standard Deviation 316.9718

SECONDARY outcome

Timeframe: At Week 48

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study. Here, overall "number of participants analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

Proportion of patients using the same Symbicort daily dose at the end of the maintenance period that they achieved at the end of the reduction period. Proportions were based on patients with non-missing Week 32 and Week 48 Symbicort doses.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=118 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Proportion of Participants Using the Same Symbicort® Daily Dose at the End of the Maintenance Period (Week 48) That They Achieved at the End of the Reduction Period (Week 32)	0.958 Proportion Interval 0.9039 to 0.9861	—

SECONDARY outcome

Timeframe: From Week 32 to Week 48

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study.

Number of patients with at least 1 exacerbation occurring from end of the reduction period to end of the maintenance period.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=125 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=43 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Number of Patients With at Least 1 Exacerbation Occurring From End of the Reduction Period to End of the Maintenance Period	5 Participants	4 Participants

SECONDARY outcome

Timeframe: Week 32, Week 40, and Week 48

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study. Here, overall "number of participants analyzed", and "number analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

Total daily ICS dose from the end of the reduction period to the end of the maintenance period.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=119 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=38 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Total Daily ICS Dose From the End of the Reduction Period to the End of the Maintenance Period Week 32	383.221 Microgram Standard Deviation 440.9649	1438.685 Microgram Standard Deviation 220.6355
Total Daily ICS Dose From the End of the Reduction Period to the End of the Maintenance Period Week 40	408.458 Microgram Standard Deviation 475.6986	1424.624 Microgram Standard Deviation 321.5752
Total Daily ICS Dose From the End of the Reduction Period to the End of the Maintenance Period Week 48	376.356 Microgram Standard Deviation 449.6614	1265.356 Microgram Standard Deviation 472.5244

SECONDARY outcome

Timeframe: From Week 32 to Week 48

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study. Here, overall "number of participants analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

Change in ACQ-5 score from end of reduction to end of maintenance is reported. This instrument contains 5 asthma symptom questions, rated from 0 (total control) to 6 (severely uncontrolled). The ACQ-5 score is the mean of the responses. Mean scores ≤0.75 indicate well controlled, scores between \>0.75 and \<1.5 indicate partly controlled, ≥1.5 indicate not well controlled asthma, and individual changes of ≥0.5 are considered to be clinically meaningful. ACQ-5 deterioration is defined as at least a 0.5 unit increase in ACQ-5 score from baseline, and a decrease of at least 0.5 units from baseline indicates improved asthma control.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=110 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=34 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Change in ACQ-5 From the End of the Reduction Period to the End of the Maintenance Period	-0.07 Score on a scale Standard Deviation 0.575	-0.20 Score on a scale Standard Deviation 0.814

SECONDARY outcome

Timeframe: From Week 32 to Week 48

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study. Here, overall "number of participants analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

Change in AQLQ(S)+12 from the end of the reduction period to the end of the maintenance period is reported. The AQLQ(S)+12 is a Patient-Reported Outcome (PRO) that measures the health-related quality of life experienced by asthma patients. The questionnaire comprises 4 separate domains (symptoms, activity limitations, emotional function, and environmental stimuli). Patients are asked to recall their experiences during the previous 2 weeks before each visit and to score each of the questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). Range of Total Score = 0 - 7 as it is an average of responses to the individual questions. High score = better quality of life, and low score = poor quality of life. Change of \>0.5 from baseline is considered a meaningful improvement in score.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=97 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=31 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Change in AQLQ(S)+12 From the End of the Reduction Period to the End of the Maintenance Period	-0.008 Score on a scale Standard Deviation 0.4720	0.060 Score on a scale Standard Deviation 0.5658

SECONDARY outcome

Timeframe: From Week 32 to Week 48

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study. Here, overall "number of participants analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

The change from the end of the reduction period to the end of the maintenance period for pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) was calculated as Week 48 pre-bronchodilator FEV1 (Liter \[L\]) minus the maintenance period baseline pre-bronchodilator FEV1 (L). The FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration, expressed in liters.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=100 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=30 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Change in FEV1 From the End of the Reduction Period to the End of the Maintenance Period	0.0089 Liter Standard Deviation 0.2320	0.0040 Liter Standard Deviation 0.2264

SECONDARY outcome

Timeframe: At Week 32 and Week 48

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study. Here, overall "number of participants analyzed" and "number analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

The number of patients meeting each individual component of the composite endpoint defining clinical remission (zero exacerbations, ACQ-5 \< 1.5, or ACQ-5 \<= 0.75, \< 10% FEV1 deterioration) at the end of reduction and maintenance periods were assessed.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=119 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=38 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Number of Patients That Met Each Composite Endpoint Defining Clinical Remission No asthma exacerbation at Week 32	108 Participants	37 Participants
Number of Patients That Met Each Composite Endpoint Defining Clinical Remission No asthma exacerbation at Week 48	101 Participants	32 Participants
Number of Patients That Met Each Composite Endpoint Defining Clinical Remission ACQ-5 <1.5 at Week 32	106 Participants	32 Participants
Number of Patients That Met Each Composite Endpoint Defining Clinical Remission ACQ-5 <1.5 at Week 48	103 Participants	32 Participants
Number of Patients That Met Each Composite Endpoint Defining Clinical Remission ACQ-5 ≤ 0.75 at Week 32	65 Participants	21 Participants
Number of Patients That Met Each Composite Endpoint Defining Clinical Remission ACQ-5 ≤ 0.75 at Week 48	68 Participants	21 Participants
Number of Patients That Met Each Composite Endpoint Defining Clinical Remission FEV1 < 10% decrease from baseline at Week 32	59 Participants	26 Participants
Number of Patients That Met Each Composite Endpoint Defining Clinical Remission FEV1 < 10% decrease from baseline at Week 48	66 Participants	23 Participants

SECONDARY outcome

Timeframe: At Week 32 and Week 48

Population: The FAS included all randomised patients, irrespective of their protocol adherence and continued participation in the study. Here, overall "number of participants analyzed" and "number analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

Clinical remission in patients at end of the reduction and maintenance periods was assessed. A remission score, assigning 1 point for each clinical remission component achieved at week 32 or week 48,was calculated for patients who met 0, 1, 2, and all 3 remission criteria (zero exacerbations,ACQ-5 \< 1.5, or ACQ-5 \<= 0.75,\< 10% FEV1 deterioration). Total remission score ranges from 0 to 3. The higher the score, the more components of remission the patient achieved.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=89 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=28 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score (Exacerbation, ACQ-5 ≤ 0.75, FEV1 < 10% decrease from baseline) at Week 32 · 0	2 Participants	0 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score (Exacerbation, ACQ-5 ≤ 0.75, FEV1 < 10% decrease from baseline) at Week 32 · 1	15 Participants	5 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score (Exacerbation, ACQ-5 ≤ 0.75, FEV1 < 10% decrease from baseline) at Week 32 · 2	40 Participants	8 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score (Exacerbation, ACQ-5 ≤ 0.75, FEV1 < 10% decrease from baseline) at Week 32 · 3	29 Participants	15 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score (Exacerbation, ACQ-5 ≤ 0.75, FEV1 < 10% decrease from baseline) at Week 48 · 0	1 Participants	1 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score (Exacerbation, ACQ-5 ≤ 0.75, FEV1 < 10% decrease from baseline) at Week 48 · 1	15 Participants	4 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score (Exacerbation, ACQ-5 ≤ 0.75, FEV1 < 10% decrease from baseline) at Week 48 · 2	41 Participants	9 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score (Exacerbation, ACQ-5 ≤ 0.75, FEV1 < 10% decrease from baseline) at Week 48 · 3	32 Participants	14 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score: Exacerbation, ACQ-5 < 1.5, FEV1 < 10% decrease from baseline at Week 32 · 0	1 Participants	0 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score: Exacerbation, ACQ-5 < 1.5, FEV1 < 10% decrease from baseline at Week 32 · 1	5 Participants	2 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score: Exacerbation, ACQ-5 < 1.5, FEV1 < 10% decrease from baseline at Week 32 · 2	32 Participants	5 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score: Exacerbation, ACQ-5 < 1.5, FEV1 < 10% decrease from baseline at Week 32 · 3	48 Participants	21 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score: Exacerbation, ACQ-5 < 1.5, FEV1 < 10% decrease from baseline at Week 48 · 0	0 Participants	0 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score: Exacerbation, ACQ-5 < 1.5, FEV1 < 10% decrease from baseline at Week 48 · 1	5 Participants	2 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score: Exacerbation, ACQ-5 < 1.5, FEV1 < 10% decrease from baseline at Week 48 · 2	36 Participants	7 Participants
Number of Patients That Met 0, 1, 2, and All 3 Composite Remission Endpoints Remission score: Exacerbation, ACQ-5 < 1.5, FEV1 < 10% decrease from baseline at Week 48 · 3	48 Participants	19 Participants

SECONDARY outcome

Timeframe: From Week 0 (randomization) to Week 48 or end of treatment (total period of study is 2.5 years)

Population: The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. Here, overall "number of participants analyzed" are the patients with available data that were evaluated for this outcome measure within the specified time frame.

The safety and tolerability of benralizumab in patients with severe asthma, while stepping down Symbicort® maintenance treatment and maintaining asthma symptom control was assessed.

Outcome measures

Outcome measures
Measure	Treatment Reduction n=125 Participants Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=42 Participants Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Number of Patients With Adverse Events or Serious Adverse Events Any AE with outcome = death	0 Participants	0 Participants
Number of Patients With Adverse Events or Serious Adverse Events Any adverse event (AE)	91 Participants	35 Participants
Number of Patients With Adverse Events or Serious Adverse Events Any serious adverse event (including events with outcome = death)	12 Participants	5 Participants
Number of Patients With Adverse Events or Serious Adverse Events Any AE leading to discontinuation of benralizumab	3 Participants	1 Participants
Number of Patients With Adverse Events or Serious Adverse Events Any AE leading to discontinuation of Symbicort	3 Participants	1 Participants
Number of Patients With Adverse Events or Serious Adverse Events Any AE leading to discontinuation of Ventolin	2 Participants	1 Participants
Number of Patients With Adverse Events or Serious Adverse Events Any AE leading to withdrawal from study	3 Participants	1 Participants

Adverse Events

Run-In Period

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Treatment Reduction

Serious events: 12 serious events

Other events: 46 other events

Deaths: 0 deaths

Reference

Serious events: 5 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Run-In Period n=167 participants at risk All patients at Screening (Visit 1), switched from their previous ICS/LABA maintenance treatment and rescue medication to high-dose Symbicort maintenance (budesonide/formoterol 400/12 μg) ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever PRN. Patients continued on this medication for the duration of the 4- to 8-week screening and run-in period.	Treatment Reduction n=125 participants at risk Patients received benralizumab 30 mg every 8 weeks (Q8W) during the study period, and high-dose Symbicort maintenance 400/12 μg ×2 inhalations BID + Ventolin (salbutamol 100 μg) reliever as needed (PRN), medium-dose Symbicort 200/6 μg ×2 inhalations BID maintenance + Symbicort 200/6 μg reliever PRN, low dose Symbicort 200/6 μg x 1 inhalation BID maintenance + Symbicort 200/6 μg reliever PRN; or Symbicort 200/6 μg reliever only, as per tapering scheme and depending on the degree of asthma control). The reduction period in this arm lasted for 32 weeks.	Reference n=42 participants at risk Patients received benralizumab 30 mg Q8W + high-dose Symbicort® 400/12 μg maintenance × 2 inhalations BID + Ventolin® (salbutamol 100 μg) reliever PRN therapy. Eligible patients randomised to the reference arm continued on high-dose Symbicort® maintenance treatment and Ventolin® reliever treatment.
Infections and infestations Bronchitis	0.00% 0/167 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.	5.6% 7/125 • Number of events 8 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.	2.4% 1/42 • Number of events 1 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.
Infections and infestations COVID-19	1.2% 2/167 • Number of events 2 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.	15.2% 19/125 • Number of events 19 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.	21.4% 9/42 • Number of events 9 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.
Infections and infestations Nasopharyngitis	1.8% 3/167 • Number of events 3 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.	8.0% 10/125 • Number of events 12 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.	16.7% 7/42 • Number of events 8 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.
Infections and infestations Rhinitis	0.00% 0/167 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.	0.80% 1/125 • Number of events 1 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.	7.1% 3/42 • Number of events 4 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/167 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.	13.6% 17/125 • Number of events 20 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.	9.5% 4/42 • Number of events 4 • Run-In period: Week -8 to -4 to Week 0 before randomization (total period of 8 weeks); Treatment Period (Treatment reduction and reference): From Week 0 (Randomization) to Week 48 or end of treatment (total period of study is 2.5 years) The safety analysis set (SAF) included all patients from the FAS who were randomized to the study and received any amount of study treatment during the ICS reduction and maintenance periods and used for all safety analyses. The run-in period includes adverse events occurring during this period reported by the patients in SAF.

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee This document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.
Publication restrictions are in place

Restriction type: OTHER