PONENTE: Study to Evaluate Efficacy and Safety of Benralizumab in Reducing Oral Corticosteroid Use in Adult Patients With Severe Asthma

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03557307
• Collaborator: (none)
• Enrollment: 598
• Locations: 144
• Arm: 1
• Actual Duration (Months): 43.7
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a study designed to evaluate efficacy and safety of Benralizumab in reducing the Oral Corticosteroid (OCS) use in adult patients with severe asthma who are receiving OCS with or without additional asthma controller medications.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Biological: Benralizumab	Phase 3

Detailed Description

This is an open-label, multicenter study designed to evaluate efficacy and safety of reducing daily oral corticosteroid (OCS) use after initiation of 30 mg dose of benralizumab administered subcutaneously (SC) in patients with severe eosinophilic asthma receiving high-dose inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) and OCS with or without additional asthma controller(s).

Study Design

• Study Type: Interventional
• Actual Enrollment: 598 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open labelOpen label
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: PONENTE: A Multicenter, Open-label, Phase 3b Efficacy and Safety Study of Benralizumab 30 mg Administered Subcutaneously to Reduce Oral Corticosteroid Use in Adult Patients With Severe Eosinophilic Asthma on High Dose Inhaled Corticosteroid Plus Long-acting β2 Agonist and Chronic Oral Corticosteroid Therapy
• Actual Study Start Date: Aug 1, 2018
• Actual Primary Completion Date: Apr 16, 2021
• Actual Study Completion Date: Mar 24, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Benralizumab Benralizumab subcutaneous injection	Biological: Benralizumab; Benralizumab subcutaneous injection

Outcome Measures

Primary Outcome Measures

1. Patients Who Achieve 100% Reduction in Daily OCS Dose [Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)]

   Patients who achieve 100% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma

2. Patients Who Achieve 100% Reduction or a Daily OCS Dose of <=5mg [Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)]

   Patients who achieve 100% reduction or a daily OCS dose of <=5mg, if reason for no further OCS reduction is Adrenal Insufficiency, that are sustained over at least 4 weeks without worsening of asthma

Secondary Outcome Measures

1. Patients Who Achieve a Daily OCS of ≤5mg [Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)]

   Patients who achieve a daily OCS dose of ≤5 mg (regardless of reason for no further OCS reduction), that are sustained over at least 4 weeks without worsening of asthma

2. Patients Who Achieve a ≥90%, ≥75%, and ≥50% Reduction in Daily OCS Dose [Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)]

   Patients who achieve a ≥90%, ≥75%, and ≥50% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma

3. Change From Baseline in Average Daily OCS Dose (mg) [Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)]

   Change from baseline in average daily OCS dose (mg) from start of OCS reduction to end of the OCS reduction phase

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 130 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Peripheral blood eosinophil count of ≥150 cells/μL assessed by central lab at Visit 1 or ≥ 300 cells/μL in the past 12 months

2. History of physician diagnosed asthma requiring continuous treatment with high dose ICS (high-dose ICS is budesonide/formoterol HFA ≥640/18 per day or equivalent, fluticasone propionate DPI > 500/day or equivalent, or authorized generics for these products) plus 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. The ICS can also be given via nebulized solution for inhalation.

3. Chronic oral corticosteroid therapy equivalent to a daily dose of at least 5 mg of prednisone, for at least 3 continuous months directly preceding Visit 1.

4. Patient should be on a stable OCS dose for at least 4 weeks prior to Visit 1.

5. Non-smokers, current smokers or former smokers with a smoking history of < or =20 pack-years at Visit 1

Exclusion Criteria:

1. Clinically important pulmonary disease other than asthma or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts

2. Known history of allergy or reaction to the study drug formulation

3. History of anaphylaxis to any biologic therapy

4. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy

5. Asthma exacerbation requiring use of systemic corticosteroids, or an increase in maintenance dose of OCS, or acute upper/lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to Visit 2 (first benralizumab dose)

6. A history of known immunodeficiency disorder including history of a positive human immunodeficiency virus (HIV) test

7. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥3 times the upper limit of normal (ULN) confirmed at Visit 1.

8. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained

9. Coincident primary adrenal failure (Addison's disease) or irreversible secondary hypoadrenalism due to another independent cause (e.g. pituitary tumour or its treatment)

10. Co-existent inflammatory conditions for which chronic OCS doses are part of their maintenance treatment such as Giant Cell Arteritis, Polymyalgia Rheumatica

11. Exclusion from genetic research may be for any of the exclusion criteria specified in the main study or allogeneic bone marrow transplant, Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection

12. Current night-shift workers

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Flagstaff	Arizona	United States	86001
2	Research Site	Los Angeles	California	United States	90025
3	Research Site	Aurora	Colorado	United States	80045
4	Research Site	Newark	Delaware	United States	19713
5	Research Site	Tampa	Florida	United States	33607
6	Research Site	Winter Park	Florida	United States	32789-4681
7	Research Site	Albany	Georgia	United States	31707
8	Research Site	Atlanta	Georgia	United States	30322
9	Research Site	Savannah	Georgia	United States	31405
10	Research Site	Normal	Illinois	United States	61761
11	Research Site	Georgetown	Kentucky	United States	40324
12	Research Site	Lakeside Park	Kentucky	United States	41017
13	Research Site	Ann Arbor	Michigan	United States	48109
14	Research Site	Minneapolis	Minnesota	United States	55402
15	Research Site	Saint Paul	Minnesota	United States	55101
16	Research Site	Saint Louis	Missouri	United States	63156
17	Research Site	New York	New York	United States	10016
18	Research Site	Chapel Hill	North Carolina	United States	27599
19	Research Site	Greenville	North Carolina	United States	27834
20	Research Site	Wilmington	North Carolina	United States	28401
21	Research Site	Winston-Salem	North Carolina	United States	27104
22	Research Site	DuBois	Pennsylvania	United States	15801
23	Research Site	North Charleston	South Carolina	United States	29406
24	Research Site	Buenos Aires		Argentina	C1121ABE
25	Research Site	Caba		Argentina	C1012AAR
26	Research Site	Cap. Fed		Argentina	1280
27	Research Site	Ciudad Autónoma de Bs. As.		Argentina	1426
28	Research Site	Ciudad Autónoma de Buenos Aire		Argentina	C1440BRR
29	Research Site	Florencio Varela		Argentina	1888
30	Research Site	Mar del Plata		Argentina	7600
31	Research Site	Mendoza		Argentina	M5500GIP
32	Research Site	Monte Grande		Argentina	1842
33	Research Site	Ranelagh		Argentina	1886
34	Research Site	Rosario		Argentina	2000
35	Research Site	Rosario		Argentina	S2000DEJ
36	Research Site	Bruxelles		Belgium	1200
37	Research Site	Erpent		Belgium	5101
38	Research Site	Gent		Belgium	9000
39	Research Site	Botucatu		Brazil	18618-970
40	Research Site	Londrina		Brazil	86057-970
41	Research Site	Maringa		Brazil	87015-000
42	Research Site	Porto Alegre		Brazil	90610-000
43	Research Site	Porto Alegre		Brazil	91350-200
44	Research Site	Salvador		Brazil	40060-330
45	Research Site	Santo Andre		Brazil	09060-650
46	Research Site	Santo Andre		Brazil	09080-110
47	Research Site	Sorocaba		Brazil	18040-425
48	Research Site	Uberlandia		Brazil	38411-186
49	Research Site	Vancouver	British Columbia	Canada	V6Z 1Y6
50	Research Site	Vancouver	CA	Canada	V5Z 4E1
51	Research Site	Ajax	Ontario	Canada	L1S 2J5
52	Research Site	Mississauga	Ontario	Canada	L5A 3V4
53	Research Site	Ottawa	Ontario	Canada	K1H 1E4
54	Research Site	Toronto	Ontario	Canada	M4V 1R2
55	Research Site	Quebec		Canada	G1V 4W2
56	Research Site	Barranquilla		Colombia	080020
57	Research Site	Bogota		Colombia	110221
58	Research Site	Cali		Colombia	76001000
59	Research Site	Cartagena		Colombia	130013
60	Research Site	Floridablanca		Colombia	681004
61	Research Site	Manizales		Colombia	17001
62	Research Site	Medellin		Colombia	5001000
63	Research Site	Herlev		Denmark	2730
64	Research Site	Hvidovre		Denmark	2650
65	Research Site	Vejle		Denmark	7100
66	Research Site	Ålborg		Denmark	9000
67	Research Site	ANGERS Cedex 9		France	49933
68	Research Site	Besancon Cedex		France	25030
69	Research Site	Colmar Cedex		France	68024
70	Research Site	Marseille		France	13300
71	Research Site	NICE Cedex 01		France	06001
72	Research Site	Orléans		France	45067
73	Research Site	Reims		France	51092
74	Research Site	Suresnes Cedex		France	92151
75	Research Site	Tours		France	37000
76	Research Site	Bamberg		Germany	96049
77	Research Site	Berlin		Germany	12203
78	Research Site	Berlin		Germany	13187
79	Research Site	Darmstadt		Germany	64283
80	Research Site	Frankfurt		Germany	60596
81	Research Site	Großhansdorf		Germany	22927
82	Research Site	Heidelberg		Germany	69126
83	Research Site	Köln		Germany	51069
84	Research Site	Leipzig		Germany	04207
85	Research Site	Lübeck		Germany	23552
86	Research Site	Magdeburg		Germany	39120
87	Research Site	München		Germany	81675
88	Research Site	Firenze		Italy	50134
89	Research Site	Milano		Italy	20162
90	Research Site	Napoli		Italy	80131
91	Research Site	Palermo		Italy	90129
92	Research Site	Pisa		Italy	56100
93	Research Site	Roma		Italy	00185
94	Research Site	Sassari		Italy	07100
95	Research Site	Tradate		Italy	21049
96	Research Site	Del. Cuauhtemoc		Mexico	06700
97	Research Site	Durango		Mexico	43080
98	Research Site	Guadalajara		Mexico	44100
99	Research Site	Guadalajara		Mexico	44130
100	Research Site	Mérida		Mexico	97070
101	Research Site	Veracruz		Mexico	91910
102	Research Site	Villahermosa		Mexico	86035
103	Research Site	Białystok		Poland	15-044
104	Research Site	Białystok		Poland	15-430
105	Research Site	Gdańsk		Poland	80-214
106	Research Site	Kraków		Poland	31-011
107	Research Site	Lubin		Poland	59-300
108	Research Site	Ostrowiec Świętokrzyski		Poland	27-400
109	Research Site	Poznań		Poland	60-693
110	Research Site	Poznań		Poland	60-823
111	Research Site	Rzeszów		Poland	35-051
112	Research Site	Sosnowiec		Poland	41-200
113	Research Site	Tarnów		Poland	33-100
114	Research Site	Wieluń		Poland	98-300
115	Research Site	Wrocław		Poland	50-449
116	Research Site	Izhevsk		Russian Federation	426061
117	Research Site	Kirov		Russian Federation	610014
118	Research Site	Moscow		Russian Federation	115478
119	Research Site	Omsk		Russian Federation	644043
120	Research Site	Omsk		Russian Federation	644112
121	Research Site	Saint Petersburg		Russian Federation	194354
122	Research Site	Saint Petersburg		Russian Federation	195257
123	Research Site	Ulyanovsk		Russian Federation	432009
124	Research Site	Cádiz		Spain	11009
125	Research Site	Marbella (Málaga)		Spain	29603
126	Research Site	Mérida		Spain	06800
127	Research Site	Ourense		Spain	32005
128	Research Site	Sant Joan Despí (Barcelona)		Spain	08970
129	Research Site	Santiago De Compostela-Coruña		Spain	15706
130	Research Site	Zaragoza		Spain	50009
131	Research Site	Lund		Sweden	221 85
132	Research Site	Kaohsiung Hsien		Taiwan	83301
133	Research Site	Kaohsiung		Taiwan	80756
134	Research Site	Taichung		Taiwan	40447
135	Research Site	Taichung		Taiwan	40705
136	Research Site	Taipei City		Taiwan	110
137	Research Site	Taipei		Taiwan	10449
138	Research Site	Taipei		Taiwan	235
139	Research Site	Yunlin		Taiwan	640
140	Research Site	Bradford		United Kingdom	BND9 6RJ
141	Research Site	Cambridge		United Kingdom	CB2 0QQ
142	Research Site	London		United Kingdom	SE1 9RT
143	Research Site	London		United Kingdom	SW3 6HP
144	Research Site	Nottingham		United Kingdom	NG5 1PB

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Oct 17, 2020
• Statistical Analysis Plan - Apr 26, 2021

More Information

Additional Information:

• CSP
• Statistical Analysis Plan (SAP)
• CSR Synopsis

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03557307
• Other Study ID Numbers: D3250C00065
• First Posted: Jun 15, 2018
• Last Update Posted: Jun 28, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by AstraZeneca: Asthma; Severe Asthma; Oral Corticosteroids
• Additional relevant MeSH terms: Asthma; Benralizumab

Study Results

Participant Flow

Recruitment Details	705 participants provided informed consent and were assigned a unique enrollment number prior to screening. Of the 705 patients screened, 598 (84.8%) were eligible to receive Benralizumab 30 mg and entered the study. All 598 (100%) patients received the study drug.
Pre-assignment Detail	In PONENTE, at the first visit, ie, the enrollment visit 1, patients were assigned an enrollment number and then evaluated regarding the protocol mandated inclusion and exclusion criteria. After screening and evaluation, only those eligible to receive Benralizumab 30 mg were assigned treatment and entered a 4 week induction phase on a stable dose of oral corticosteroids (OCS).

Arm/Group Title	Benra 30 mg
Arm/Group Description	Benralizumab 30 mg administered subcutaneously every 4 weeks
Period Title: To End of OCS Reduction Phase
STARTED	598
COMPLETED	563
NOT COMPLETED	35
Period Title: To End of OCS Reduction Phase
STARTED	563
COMPLETED	536
NOT COMPLETED	27

Baseline Characteristics

Arm/Group Title	Benra 30 mg
Arm/Group Description	Benralizumab 30 mg administered subcutaneously every 4 weeks
Overall Participants	598
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.3 (13.59)
Sex: Female, Male (Count of Participants)
Female	383 64%
Male	215 36%
Race/Ethnicity, Customized (Count of Participants)
White	475 79.4%
Black or African American	26 4.3%
Asian	29 4.8%
Native Hawaiian or other Pacific Islander	1 0.2%
American Indian or Alaska Native	46 7.7%
Other	12 2%

Outcome Measures

1. Primary Outcome

Title	Patients Who Achieve 100% Reduction in Daily OCS Dose
Description	Patients who achieve 100% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma
Time Frame	Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)

Outcome Measure Data

Analysis Population Description

Full analysis set - All enrolled patients who received at least one dose of benralizumab are included in the FAS, irrespective of their protocol adherence and continued participation in the study.

Arm/Group Title	Benra 30 mg
Arm/Group Description	Benralizumab 30 mg administered subcutaneously every 4 weeks
Measure Participants	598
Count of Participants [Participants]	376 62.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage
	Estimated Value	62.9
	Confidence Interval	(2-Sided) 95%; 58.86 to 66.76
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage of patients who achieved 100% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma

2. Primary Outcome

Title	Patients Who Achieve 100% Reduction or a Daily OCS Dose of <=5mg
Description	Patients who achieve 100% reduction or a daily OCS dose of <=5mg, if reason for no further OCS reduction is Adrenal Insufficiency, that are sustained over at least 4 weeks without worsening of asthma
Time Frame	Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)

Outcome Measure Data

Analysis Population Description

All enrolled patients who received at least one dose of benralizumab are included in the FAS, irrespective of their protocol adherence and continued participation in the study.

Arm/Group Title	Benra 30 mg
Arm/Group Description	Benralizumab 30 mg administered subcutaneously every 4 weeks
Measure Participants	598
Count of Participants [Participants]	490 81.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage
	Estimated Value	81.9
	Confidence Interval	(2-Sided) 95%; 78.62 to 84.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage of patients who achieve 100% reduction or a daily OCS dose of <=5mg, if reason for no further OCS reduction is Adrenal Insufficiency, that are sustained over at least 4 weeks without worsening of asthma

3. Secondary Outcome

Title	Patients Who Achieve a Daily OCS of ≤5mg
Description	Patients who achieve a daily OCS dose of ≤5 mg (regardless of reason for no further OCS reduction), that are sustained over at least 4 weeks without worsening of asthma
Time Frame	Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)

Outcome Measure Data

Analysis Population Description

Full analysis set - All enrolled patients who received at least one dose of benralizumab are included in the FAS, irrespective of their protocol adherence and continued participation in the study.

Arm/Group Title	Benra 30 mg
Arm/Group Description	Benralizumab 30 mg administered subcutaneously every 4 weeks
Measure Participants	598
Count of Participants [Participants]	547 91.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage
	Estimated Value	91.5
	Confidence Interval	(2-Sided) 95%; 88.94 to 93.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage of patients who achieve a daily OCS dose of ≤5 mg (regardless of reason for no further OCS reduction), that are sustained over at least 4 weeks without worsening of asthma

4. Secondary Outcome

Title	Patients Who Achieve a ≥90%, ≥75%, and ≥50% Reduction in Daily OCS Dose
Description	Patients who achieve a ≥90%, ≥75%, and ≥50% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma
Time Frame	Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)

Outcome Measure Data

Analysis Population Description

Full analysis set - All enrolled patients who received at least one dose of benralizumab are included in the FAS, irrespective of their protocol adherence and continued participation in the study.

Arm/Group Title	Benra 30 mg
Arm/Group Description	Benralizumab 30 mg administered subcutaneously every 4 weeks
Measure Participants	598
≥90% reduction	383 64%
≥75% reduction	412 68.9%
≥50% reduction	489 81.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage
	Estimated Value	64.0
	Confidence Interval	(2-Sided) 95%; 60.06 to 67.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage of patients who achieve >=90% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage
	Estimated Value	68.9
	Confidence Interval	(2-Sided) 95%; 65.02 to 72.59
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage of patients who achieve >=75% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage
	Estimated Value	81.8
	Confidence Interval	(2-Sided) 95%; 78.44 to 84.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage of patients who achieve >=50% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma

5. Secondary Outcome

Title	Change From Baseline in Average Daily OCS Dose (mg)
Description	Change from baseline in average daily OCS dose (mg) from start of OCS reduction to end of the OCS reduction phase
Time Frame	Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)

Outcome Measure Data

Analysis Population Description

Full analysis set - All enrolled patients who received at least one dose of benralizumab are included in the FAS, irrespective of their protocol adherence and continued participation in the study.

Arm/Group Title	Benra 30 mg
Arm/Group Description	Benralizumab 30 mg administered subcutaneously every 4 weeks
Measure Participants	593
Mean (95% Confidence Interval) [mg]	-8.50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage change from baseline
	Estimated Value	-76.92
	Confidence Interval	(2-Sided) 95%; -79.90 to -73.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage change from baseline in daily OCS dose at the end of OCS reduction phase

Adverse Events

Time Frame	From first dose of study drug until end of study, with an average of 405 days.
Arm/Group Title	Benra 30 mg
Arm/Group Description	Benralizumab 30 mg administered subcutaneously every 4 weeks
All Cause Mortality
	Benra 30 mg
	Affected / at Risk (%)	# Events
Total	5/598 (0.8%)
Serious Adverse Events
	Benra 30 mg
	Affected / at Risk (%)	# Events
Total	89/598 (14.9%)
Cardiac disorders
Acute myocardial infarction	4/598 (0.7%)	4
Angina unstable	2/598 (0.3%)	2
Cardiac arrest	2/598 (0.3%)	2
Cardiac failure congestive	1/598 (0.2%)	1
Coronary artery disease	1/598 (0.2%)	1
Myocardial ischaemia	1/598 (0.2%)	1
Ventricular extrasystoles	1/598 (0.2%)	1
Ear and labyrinth disorders
Meniere's disease	1/598 (0.2%)	1
Gastrointestinal disorders
Abdominal pain	1/598 (0.2%)	1
Anal fistula	1/598 (0.2%)	1
Ileus	2/598 (0.3%)	2
Pancreatitis	1/598 (0.2%)	1
Pancreatitis acute	1/598 (0.2%)	2
General disorders
Sudden cardiac death	1/598 (0.2%)	1
Hepatobiliary disorders
Cholelithiasis	1/598 (0.2%)	1
Infections and infestations
COVID-19	1/598 (0.2%)	1
Chronic sinusitis	2/598 (0.3%)	2
Diverticulitis	2/598 (0.3%)	2
Gastroenteritis	1/598 (0.2%)	1
H1N1 influenza	1/598 (0.2%)	1
Haemophilus infection	1/598 (0.2%)	1
Infected bite	1/598 (0.2%)	1
Influenza	5/598 (0.8%)	5
Lower respiratory tract infection bacterial	1/598 (0.2%)	1
Pelvic abscess	1/598 (0.2%)	1
Peritonitis	1/598 (0.2%)	1
Pneumonia	11/598 (1.8%)	11
Pneumonia bacterial	2/598 (0.3%)	2
Pneumonia haemophilus	2/598 (0.3%)	2
Pneumonia influenzal	1/598 (0.2%)	2
Pneumonia pseudomonal	1/598 (0.2%)	1
Respiratory tract infection	1/598 (0.2%)	1
Respiratory tract infection bacterial	1/598 (0.2%)	1
Sepsis	3/598 (0.5%)	3
Urosepsis	1/598 (0.2%)	1
Injury, poisoning and procedural complications
Alcohol poisoning	1/598 (0.2%)	1
Craniocerebral injury	1/598 (0.2%)	1
Humerus fracture	1/598 (0.2%)	1
Multiple fractures	1/598 (0.2%)	1
Post procedural haemorrhage	1/598 (0.2%)	1
Rib fracture	1/598 (0.2%)	1
Spinal fracture	1/598 (0.2%)	1
Tendon rupture	1/598 (0.2%)	1
Investigations
Oxygen saturation decreased	1/598 (0.2%)	1
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/598 (0.2%)	1
Type 2 diabetes mellitus	1/598 (0.2%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/598 (0.2%)	1
Osteonecrosis	1/598 (0.2%)	1
Polymyalgia rheumatica	1/598 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	1/598 (0.2%)	1
Basal cell carcinoma	1/598 (0.2%)	1
Malignant glioma	1/598 (0.2%)	1
Neurofibroma	1/598 (0.2%)	1
Uterine leiomyoma	1/598 (0.2%)	1
Nervous system disorders
Apallic syndrome	1/598 (0.2%)	1
Carotid artery aneurysm	1/598 (0.2%)	1
Dizziness postural	1/598 (0.2%)	1
Generalised tonic-clonic seizure	1/598 (0.2%)	1
Sciatica	1/598 (0.2%)	1
Renal and urinary disorders
Acute kidney injury	1/598 (0.2%)	1
Reproductive system and breast disorders
Breast calcifications	1/598 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/598 (0.2%)	1
Aspirin-exacerbated respiratory disease	1/598 (0.2%)	1
Asthma	23/598 (3.8%)	33
Atelectasis	1/598 (0.2%)	1
Chronic rhinosinusitis with nasal polyps	1/598 (0.2%)	1
Dyspnoea	1/598 (0.2%)	1
Haemoptysis	1/598 (0.2%)	1
Pharyngeal swelling	1/598 (0.2%)	1
Respiratory failure	1/598 (0.2%)	1
Vascular disorders
Embolism arterial	1/598 (0.2%)	1
Hypertensive emergency	1/598 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Benra 30 mg
	Affected / at Risk (%)	# Events
Total	181/598 (30.3%)
General disorders
Influenza like illness	33/598 (5.5%)	34
Infections and infestations
Nasopharyngitis	64/598 (10.7%)	92
Sinusitis	19/598 (3.2%)	22
Upper respiratory tract infection	25/598 (4.2%)	28
Viral upper respiratory tract infection	28/598 (4.7%)	31
Nervous system disorders
Headache	29/598 (4.8%)	38
Vascular disorders
Hypertension	21/598 (3.5%)	21

Limitations/Caveats

During COVID-19 pandemic, for ongoing patients, patient dosing, and scheduled visits are inevitable impacted. But the primary endpoint is not impacted.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

≥ 60 days prior to submission of material for publication/presentation, Institution and PI shall jointly provide AZ with material for review. No publication/presentation may include any of AZ's Confidential Information without AZ's written approval. AZ can request Inst. and PI to withhold material from submission for publication/presentation for an additional 90 days to allow AZ to establish and preserve its proprietary rights in the material being submitted for publication or presentation.