TERRANOVA: Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With Exacerbation History

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT02155660

Collaborator

MedImmune LLC (Industry)

2,255

Enrollment

356

Locations

Arms

45.5

Actual Duration (Months)

6.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to determine if benralizumab reduces COPD exacerbation rate in symptomatic patients with moderate to very severe COPD who are receiving standard of care therapies.

Condition or Disease	Intervention/Treatment	Phase
Moderate to Very Severe Chronic Obstructive Pulmonary Disease	Drug: Benralizumab Arm A Drug: Benralizumab Arm B Drug: Benralizumab Arm C Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

2255 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomised, Double-blind, Double Dummy, 56 Week Placebo-controlled, Multicentre, Parallel Group, Phase 3 Study Evaluating Efficacy/Safety of 3 Benralizumab Doses in Patients With Moderate to Very Severe COPD With Previous Exacerbations.

Actual Study Start Date :

Jun 25, 2014

Actual Primary Completion Date :

Apr 9, 2018

Actual Study Completion Date :

Apr 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Benralizumab Arm A Benralizumab administered subcutaneously	Drug: Benralizumab Arm A Benralizumab subcutaneously on study week 0 until study week 48 inclusive
Experimental: Benralizumab Arm B Benralizumab administered subcutaneously	Drug: Benralizumab Arm B Benralizumab subcutaneously on study week 0 until study week 48 inclusive
Experimental: Benralizumab Arm C Benralizumab administered subcutaneously	Drug: Benralizumab Arm C Benralizumab subcutaneously on study week 0 until study week 48 inclusive
Placebo Comparator: Placebo Placebo administered subcutaneously	Drug: Placebo Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Outcome Measures

Primary Outcome Measures

Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL [Immediately following the first IP dose through week 56]
A COPD exacerbation is defined by symptomatic worsening of COPD requiring: Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or Use of antibiotics; and/or An inpatient hospitalization or death due to COPD Annual COPD exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.

Secondary Outcome Measures

Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS<220/uL [Immediately following the first IP dose through week 56]
A COPD exacerbation is defined by symptomatic worsening of COPD requiring: Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or Use of antibiotics; and/or An inpatient hospitalization or death due to COPD Annual COPD exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.
Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline EOS>=220/uL [First IP up to end of treatment Week 56]
Pre-bronchodilator FEV1 (L) is collected at Weeks 0, 4, 8, 16, 24, 32, 40, 48, and 56. Baseline is the last non-missing value with quality (acceptable or borderline quality grade) prior to the first dose of study treatment.
Mean Change From Baseline in SGRQ Total Score for Patients With Baseline EOS>=220/uL [First IP up to Week 56]
SGRQ is from 50-item PRO instrument. The SGRQ total score is expressed as a percentage of overall impairment, in which 100% means the worst possible health status and 0 indicates the best possible health status.
Mean Change From Baseline in CAT Total Score for Patients With Baseline EOS>=220/uL [First IP up to Week 56]
CAT is an 8-item PRO developed to measure the impact of COPD on health status. The instrument uses semantic differential six-point response scales. A CAT total score is the sum of item responses. Score ranges from 0 to 40 with higher scores indicative of greater COPD impact on health status.
Mean Change From Baseline in E-RS: COPD Total Score for Patients With Baseline EOS>=220/uL [First IP up to Week 56]
The E-RS: COPD is an 11-item PRO developed to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS: COPD item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity.
Mean Change From Baseline in Total Rescue Medication Use (Number of Puffs Per Day) for Patients With Baseline EOS>=220/uL [First IP up to Week 56]
The number of rescue medication inhalations and nebulizer treatments taken are recorded by the patient in the eDiary twice daily. Total rescue medication use is the sum of daytime and night-time use.
Mean Change From Baseline in Proportion of Nights With Awakenings Due to Respiratory Symptoms for Patients With Baseline EOS>=220/uL [First IP up to Week 56]
Change from baseline to Week 56 in proportion of nights with awakenings due to respiratory symptoms.
Number of Participants by Number of COPD Exacerbations Based on EXACT-PRO for Patients With Baseline EOS>=220/uL [Immediately following first IP up to week 56]
The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while considering their experiences "today". The daily EXACT-PRO total score is recorded and has a range of 0-100 with higher scores indicative of greater severity. COPD exacerbation event frequency is calculated based on comparison of the baseline score with daily total scores. An increase of EXACT-PRO total score ≥9 for 3 days or ≥12 for 2 days indicates a COPD exacerbation event has occurred.
Severity of EXACT-PRO for Patients With Baseline EOS>=220/uL [Immediately following first IP up to week 56]
The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while considering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. Severity of the study is the highest score of EXACT-PRO.
Duration of COPD Exacerbation Based on EXACT-PRO Score for Patients With Baseline EOS>=220/uL [Immediately following first IP up to week 56]
The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while considering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. COPD exacerbation event frequency is identified by comparing the baseline score with daily total scores. An increase in EXACT-PRO total score ≥9 for 3 days or ≥12 for 2 days indicate an event has occurred. Event duration is calculated after identification of the following five parameters: 1) onset; 2) three-day rolling average; 3) maximum observed value; 4) threshold for improvement; and 5) recovery. That is, duration of the exacerbation is the time elapse between onset and recovery of the event.
Annual EXACT-PRO Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL [Immediately following the first IP dose through week 56]
The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while considering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. Event frequency is calculated by comparing the baseline with daily total scores. An increase in EXACT-PRO total score ≥9 for 3 days or ≥12 for 2 days indicate an event has occurred. Annual EXACT-PRO exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.
Number of Participants Having at Least 1 COPD Exacerbation for Patients With Baseline EOS>=220/uL [Immediately following first IP dose up to week 56]
A COPD exacerbation is defined by symptomatic worsening COPD requiring systemic corticosteroids, antibiotics, or an inpatient hospitalization/death due to COPD.
Time to First COPD Exacerbation [Immediately following IP dose to Week 56]
Time to first COPD exacerbation is from the randomization date to the first occurrence of COPD exacerbation.
Annual COPD Exacerbation Rate Associated With ER or Hospitalization Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL [Immediately following the first IP dose through week 56]
Annual COPD exacerbations rate that result in ER or hospitalization is calculated by number of exacerbations resulting ER or hospitalization divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.
Number of Participants Had COPD-related Healthcare Encounter for Patient With Baseline EOS>=220/uL [Immediately following first IP dose up to Week 56]
Types of healthcare encounter: Hospitalisations (inc. intensive care and/or general care), Emergency department visits, Unscheduled outpatients visits, Home visits, Telephone calls, and ambulance transports.
Duration of Study Treatment Administration [From first dose date to last dose date, 48 weeks per protocol.]
Duration of study treatment is calculated from first dose date to last dose date + 1 day.
Serum Concentration of Benralizumab [Pre-first dose and pre-dose at end of treatment (week 56).]
PK serum samples were collected pre-dose at each visit.
Immunogenicity of Benralizumab [Pre-treatment until end of follow-up, week 60 per protocol.]
Anti-drug antibody (ADA) responses such as ADA prevalence, ADA incidence, ADA persistently positive counts, etc. were presented.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:.

Informed consent.
Subjects 40-85 y.o.
Moderate to very severe COPD with Post Bronchodilator (BD) FEV1>20% and ≤65%.

-≥2 moderate or ≥1 severe COPD exacerbation(s) required treatment or hospitalization within 2-52 weeks prior to Visit1.

Modified Medical Research Council (mMRC) score ≥1 at Visit 1.
Treatment with double or triple therapy throughout the year prior to Visit 1, constant 2 weeks prior to Visit 1.
Tobacco history of ≥10 pack-years.
Women of childbearing potential must use a highly effective form of birth control from Visit 1 until 16 weeks after their last dose, and negative serum pregnancy test result at Visit 1.
Male subjects who are sexually active must be surgically sterile one year prior to Visit 1 or use an adequate method of contraception from the first Investigational Product (IP) dose until 16 weeks after their last dose.
Compliance with maintenance therapy during run-in ≥70%.
Blood eosinophils due to subject's stratification and cap for blood eosinophil levels.When any eosinophil cohort is full, subjects in the completed cohort will not be randomised and will be withdrawn from the study.

Exclusion criteria:

Clinically important pulmonary disease other than COPD or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
Any disorder or major physical impairment that is not stable by Investigator opinion and/or could affect: - subject safety-study findings or their interpretation or subject's ability to complete the entire study duration.
Unstable ischemic heart disease, arrhythmia, cardiomyopathy, or other relevant cardiovascular disorder that in Investigator's judgment may put the patient at risk or negatively affect the study outcome.
Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 2 weeks prior to Visit1 or during the enrolment and run-in period.
Acute upper or lower respiratory infection requiring antibiotics within 2 weeks prior to Visit1 or during the enrolment and run-in period.
Pneumonia within 8 weeks prior to Visit1 or during the enrolment and run-in period.
Pregnant, breastfeeding, or lactating women.
Risk factors for pneumonia
History of anaphylaxis to any other biologic therapy.
Long term oxygen therapy with signs and/or symptoms of cor pulmonale, right ventricular failure.
Use of immunosuppressive medication within 2 weeks prior to Visit1 and/or during the enrolment and run-in period.
Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to Visit 1.
Evidence of active tuberculosis (TB) without an appropriate course of treatment.
Lung volume reduction surgery within the 6 months prior to Visit 1. History of partial or total lung resection (single lobe or segmentectomy is acceptable).
Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA) guidelines or other accepted guidelines.
Previous treatment with benralizumab.
Helminth parasitic infection diagnosed within 24 weeks prior to Visit 1.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35216
2	Research Site	Gulf Shores	Alabama	United States	36542
3	Research Site	Montgomery	Alabama	United States	36117
4	Research Site	Flagstaff	Arizona	United States	86001
5	Research Site	Phoenix	Arizona	United States	85018
6	Research Site	Anaheim	California	United States	92801
7	Research Site	Arcadia	California	United States	91007
8	Research Site	Bakersfield	California	United States	93301
9	Research Site	Fresno	California	United States	93721
10	Research Site	Fullerton	California	United States	92835
11	Research Site	Hawaiian Gardens	California	United States	90716
12	Research Site	Huntington Beach	California	United States	92647
13	Research Site	Los Angeles	California	United States	90048
14	Research Site	Northridge	California	United States	91324
15	Research Site	Palmdale	California	United States	93551
16	Research Site	Peninsula	California	United States	90505
17	Research Site	Placentia	California	United States	92870
18	Research Site	Rolling Hills Estates	California	United States	90274
19	Research Site	Westminster	California	United States	92683
20	Research Site	Centennial	Colorado	United States	80112
21	Research Site	Colorado Springs	Colorado	United States	80907
22	Research Site	Denver	Colorado	United States	80246
23	Research Site	Chiefland	Florida	United States	32626
24	Research Site	Clearwater	Florida	United States	33759
25	Research Site	Clearwater	Florida	United States	33765
26	Research Site	Coconut Creek	Florida	United States	33066
27	Research Site	Coral Gables	Florida	United States	33134
28	Research Site	Daytona Beach	Florida	United States	32117
29	Research Site	DeBary	Florida	United States	32713
30	Research Site	DeLand	Florida	United States	32720
31	Research Site	Doral	Florida	United States	33172
32	Research Site	Edgewater	Florida	United States	32132
33	Research Site	Fort Lauderdale	Florida	United States	33308
34	Research Site	Hialeah	Florida	United States	33010
35	Research Site	Hialeah	Florida	United States	33012
36	Research Site	Hialeah	Florida	United States	33013
37	Research Site	Homestead	Florida	United States	33130
38	Research Site	Jacksonville	Florida	United States	32204
39	Research Site	Kissimmee	Florida	United States	34744
40	Research Site	Miami	Florida	United States	33126
41	Research Site	Miami	Florida	United States	33144
42	Research Site	Miami	Florida	United States	33147
43	Research Site	Miami	Florida	United States	33155
44	Research Site	Miami	Florida	United States	33165
45	Research Site	Miami	Florida	United States	33174
46	Research Site	Miami	Florida	United States	33186
47	Research Site	Pensacola	Florida	United States	32504
48	Research Site	Port Charlotte	Florida	United States	33952
49	Research Site	Sarasota	Florida	United States	34239
50	Research Site	South Miami	Florida	United States	33143
51	Research Site	Atlanta	Georgia	United States	30331
52	Research Site	Blue Ridge	Georgia	United States	30513
53	Research Site	Lawrenceville	Georgia	United States	30046
54	Research Site	Woodstock	Georgia	United States	30189
55	Research Site	Nampa	Idaho	United States	83687
56	Research Site	Evergreen Park	Illinois	United States	60805
57	Research Site	O'Fallon	Illinois	United States	62269
58	Research Site	Peoria	Illinois	United States	61602
59	Research Site	River Forest	Illinois	United States	60305
60	Research Site	Topeka	Kansas	United States	66606
61	Research Site	Henderson	Kentucky	United States	42420
62	Research Site	Owensboro	Kentucky	United States	42303
63	Research Site	Opelousas	Louisiana	United States	70570
64	Research Site	Shreveport	Louisiana	United States	71106
65	Research Site	Sunset	Louisiana	United States	70584
66	Research Site	Bangor	Maine	United States	04401
67	Research Site	Lutherville	Maryland	United States	21093
68	Research Site	White Marsh	Maryland	United States	21162
69	Research Site	Fall River	Massachusetts	United States	02720
70	Research Site	Marlborough	Massachusetts	United States	01752
71	Research Site	Buckley	Michigan	United States	49620
72	Research Site	Kalamazoo	Michigan	United States	49009
73	Research Site	Troy	Michigan	United States	48085
74	Research Site	Edina	Minnesota	United States	55435
75	Research Site	Fridley	Minnesota	United States	55432
76	Research Site	Woodbury	Minnesota	United States	55125
77	Research Site	Picayune	Mississippi	United States	39466
78	Research Site	Port Gibson	Mississippi	United States	39150
79	Research Site	Belton	Missouri	United States	64012
80	Research Site	Florissant	Missouri	United States	63033
81	Research Site	Saint Louis	Missouri	United States	63136
82	Research Site	Missoula	Montana	United States	59808
83	Research Site	Fremont	Nebraska	United States	68025
84	Research Site	Omaha	Nebraska	United States	68124
85	Research Site	Las Vegas	Nevada	United States	89146
86	Research Site	Marlton	New Jersey	United States	08053
87	Research Site	Union	New Jersey	United States	07083
88	Research Site	Bronx	New York	United States	10459
89	Research Site	Bronx	New York	United States	10461
90	Research Site	Brooklyn	New York	United States	11236
91	Research Site	Great Neck	New York	United States	11023
92	Research Site	Mineola	New York	United States	11501
93	Research Site	New Windsor	New York	United States	12553
94	Research Site	New York	New York	United States	10016
95	Research Site	Potsdam	New York	United States	13676
96	Research Site	Burlington	North Carolina	United States	27215
97	Research Site	Calabash	North Carolina	United States	28467
98	Research Site	Charlotte	North Carolina	United States	28277
99	Research Site	Hickory	North Carolina	United States	28601
100	Research Site	Mooresville	North Carolina	United States	28117
101	Research Site	New Bern	North Carolina	United States	28562
102	Research Site	Shelby	North Carolina	United States	28150
103	Research Site	Chardon	Ohio	United States	44024
104	Research Site	Cincinnati	Ohio	United States	45242
105	Research Site	Columbus	Ohio	United States	43213
106	Research Site	Columbus	Ohio	United States	43214
107	Research Site	Marion	Ohio	United States	43302
108	Research Site	Toledo	Ohio	United States	43617
109	Research Site	Oklahoma City	Oklahoma	United States	73103
110	Research Site	Oklahoma City	Oklahoma	United States	73112
111	Research Site	Clackamas	Oregon	United States	97015-6804
112	Research Site	Medford	Oregon	United States	97504
113	Research Site	Monroeville	Pennsylvania	United States	15146
114	Research Site	Philadelphia	Pennsylvania	United States	19142
115	Research Site	Pittsburgh	Pennsylvania	United States	15213
116	Research Site	Pittsburgh	Pennsylvania	United States	15243
117	Research Site	Uniontown	Pennsylvania	United States	15401
118	Research Site	Charleston	South Carolina	United States	29412
119	Research Site	Hodges	South Carolina	United States	29653
120	Research Site	Spartanburg	South Carolina	United States	29303
121	Research Site	Rapid City	South Dakota	United States	57702
122	Research Site	Tullahoma	Tennessee	United States	37388
123	Research Site	Corsicana	Texas	United States	75110
124	Research Site	Dallas	Texas	United States	75216
125	Research Site	Duncanville	Texas	United States	75116
126	Research Site	Fort Worth	Texas	United States	76104
127	Research Site	Houston	Texas	United States	77024
128	Research Site	Houston	Texas	United States	77034
129	Research Site	Houston	Texas	United States	77036
130	Research Site	Houston	Texas	United States	77043
131	Research Site	Houston	Texas	United States	77055
132	Research Site	Houston	Texas	United States	77063
133	Research Site	Houston	Texas	United States	78756
134	Research Site	Huntsville	Texas	United States	77340
135	Research Site	Killeen	Texas	United States	76543
136	Research Site	Lampasas	Texas	United States	76550
137	Research Site	Longview	Texas	United States	75604
138	Research Site	Lufkin	Texas	United States	75904
139	Research Site	McKinney	Texas	United States	75069
140	Research Site	McKinney	Texas	United States	75071
141	Research Site	Plano	Texas	United States	75093
142	Research Site	Sealy	Texas	United States	77474
143	Research Site	Bountiful	Utah	United States	84010
144	Research Site	Salt Lake City	Utah	United States	84102
145	Research Site	Abingdon	Virginia	United States	24210
146	Research Site	Richmond	Virginia	United States	23220
147	Research Site	Richmond	Virginia	United States	23235
148	Research Site	Everett	Washington	United States	98208
149	Research Site	Tacoma	Washington	United States	98405
150	Research Site	Kingwood	West Virginia	United States	26357
151	Research Site	Morgantown	West Virginia	United States	26505
152	Research Site	Buenos Aires		Argentina	C1414AIF
153	Research Site	Caba		Argentina	1426
154	Research Site	Caba		Argentina	C1056ABJ
155	Research Site	Caba		Argentina	C1425BEN
156	Research Site	Caba		Argentina	C1431FWO
157	Research Site	Ciudad Autónoma de Buenos Aire		Argentina	C1440BRR
158	Research Site	Ciudad de Buenos Aires		Argentina	1425
159	Research Site	Concepción del Uruguay		Argentina	3260
160	Research Site	Corrientes		Argentina	3400
161	Research Site	Córdoba		Argentina	X5003DCE
162	Research Site	Córdoba		Argentina	X5014KEH
163	Research Site	Florencio Varela		Argentina	1888
164	Research Site	Florida		Argentina	1638
165	Research Site	Mar del Plata		Argentina	7600
166	Research Site	Mar del Plata		Argentina	B7600GNY
167	Research Site	Mendoza		Argentina	5500
168	Research Site	Mendoza		Argentina	M5500GIP
169	Research Site	Nueve de julio		Argentina	B6500EZL
170	Research Site	Quilmes		Argentina	B1878FNR
171	Research Site	Rosario		Argentina	S2000DEJ
172	Research Site	San Fernando		Argentina	1646
173	Research Site	San Miguel de Tucuman		Argentina	T4000IAR
174	Research Site	Clayton		Australia	3168
175	Research Site	Gosford		Australia	2250
176	Research Site	Murdoch		Australia	6150
177	Research Site	Nedlands		Australia	6009
178	Research Site	New Lambton		Australia	2310
179	Research Site	Woolloongabba		Australia	4102
180	Research Site	Brussels		Belgium	1020
181	Research Site	Genk		Belgium	3600
182	Research Site	Jambes		Belgium	5100
183	Research Site	Leuven		Belgium	3000
184	Research Site	Malmedy		Belgium	4960
185	Research Site	Turnhout		Belgium	2300
186	Research Site	Veurne		Belgium	8630
187	Research Site	Fortaleza		Brazil	60864190
188	Research Site	Porto Alegre		Brazil	90035-074
189	Research Site	Porto Alegre		Brazil	90470-340
190	Research Site	Porto Alegre		Brazil	90610-000
191	Research Site	Porto Alegre		Brazil	91350-200
192	Research Site	Rio de Janeiro		Brazil	22271-100
193	Research Site	Santo Andre		Brazil	09080-110
194	Research Site	Sao Paulo		Brazil	04020060
195	Research Site	Sao Paulo		Brazil	04023-062
196	Research Site	Sao Paulo		Brazil	05403-000
197	Research Site	Sorocaba		Brazil	18040-425
198	Research Site	Vitória		Brazil	29055-450
199	Research Site	Dupnitsa		Bulgaria	2600
200	Research Site	Kozloduy		Bulgaria	3320
201	Research Site	Pazardzhik		Bulgaria	4400
202	Research Site	Pernik		Bulgaria	2300
203	Research Site	Petrich		Bulgaria	2850
204	Research Site	Plovdiv		Bulgaria	4002
205	Research Site	Ruse		Bulgaria	7002
206	Research Site	Sandanski		Bulgaria	2800
207	Research Site	Silistra		Bulgaria
208	Research Site	Sofia		Bulgaria	1002
209	Research Site	Sofia		Bulgaria	1408
210	Research Site	Vidin		Bulgaria	3700
211	Research Site	Vratsa		Bulgaria	3000
212	Research Site	Yambol		Bulgaria	8600
213	Research Site	Curico		Chile	3341643
214	Research Site	Quillota		Chile	2260000
215	Research Site	Santiago		Chile	7500698
216	Research Site	Santiago		Chile	7500800
217	Research Site	Talca		Chile	3465584
218	Research Site	Armenia		Colombia	630004
219	Research Site	Barranquilla		Colombia	80001
220	Research Site	Bogota		Colombia	111511
221	Research Site	Bogotá		Colombia	110221
222	Research Site	Bogotá		Colombia
223	Research Site	Cali		Colombia	76001000
224	Research Site	Manizales		Colombia	17001
225	Research Site	Medellin		Colombia	5001000
226	Research Site	Medillin		Colombia
227	Research Site	Petrinja		Croatia	44250
228	Research Site	Aarhus N		Denmark	8200
229	Research Site	København NV		Denmark	2400
230	Research Site	Næstved		Denmark	4700
231	Research Site	Odense C		Denmark	5000
232	Research Site	Roskilde		Denmark	4000
233	Research Site	Silkeborg		Denmark	8600
234	Research Site	Bois Guillaume		France	76031
235	Research Site	Brest Cedex		France	29609
236	Research Site	La Tronche		France	38700
237	Research Site	Lille cedex		France	59037
238	Research Site	Lyon Cedex 04		France	69317
239	Research Site	Marseille		France	13915
240	Research Site	Montpellier		France	34295
241	Research Site	NIMES Cedex 9		France	30029
242	Research Site	Orléans Cedex 2		France	45100
243	Research Site	Pessac		France	33604
244	Research Site	Haifa		Israel	34362
245	Research Site	Jerusalem		Israel	91120
246	Research Site	Jerusalem		Israel	9372212
247	Research Site	Petach Tikva		Israel	49100
248	Research Site	Rehovot		Israel	7661041
249	Research Site	Tel Aviv		Israel	IL-
250	Research Site	Durango		Mexico	43080
251	Research Site	Guadalajara		Mexico	44130
252	Research Site	Guadalajara		Mexico	44200
253	Research Site	Mexico		Mexico	14050
254	Research Site	Monterrey		Mexico	64460
255	Research Site	Monterrey		Mexico	66465
256	Research Site	Auckland		New Zealand	0626
257	Research Site	Auckland		New Zealand	2025
258	Research Site	Dunedin		New Zealand	9016
259	Research Site	Greenlane		New Zealand	1051
260	Research Site	Hamilton West		New Zealand	3204
261	Research Site	Tauranga		New Zealand	3112
262	Research Site	Bodø		Norway	N-8092
263	Research Site	Kolbjørnsvik		Norway	N-4816
264	Research Site	Svelvik		Norway	3060
265	Research Site	Cusco		Peru	CUSCO 01
266	Research Site	Lima		Peru	15033
267	Research Site	Lima		Peru	41
268	Research Site	Lima		Peru	L27
269	Research Site	Lima		Peru	L41
270	Research Site	Lima		Peru	LIMA 1
271	Research Site	Lima		Peru	LIMA 21
272	Research Site	Lima		Peru	LIMA 31
273	Research Site	Lima		Peru	LIMA 33
274	Research Site	Piura		Peru
275	Research Site	Iloilo City		Philippines	5000
276	Research Site	Lipa City		Philippines
277	Research Site	Manila		Philippines	1000
278	Research Site	Quezon City		Philippines	1100
279	Research Site	Quezon City		Philippines	1101
280	Research Site	Quezon City		Philippines	1109
281	Research Site	Białystok		Poland	15-044
282	Research Site	Białystok		Poland	15-351
283	Research Site	Bydgoszcz		Poland	85-231
284	Research Site	Gdańsk		Poland	80-952
285	Research Site	Gorzów Wlkp		Poland	66-400
286	Research Site	Grodzisk Mazowiecki		Poland	05-825
287	Research Site	Karczew		Poland	05-480
288	Research Site	Katowice		Poland	40-648
289	Research Site	Kraków		Poland	30-901
290	Research Site	Ostrowiec Świętokrzyski		Poland	27-400
291	Research Site	Ostrów Wielkopolski		Poland	63-400
292	Research Site	Ruda Śląska		Poland	41-707
293	Research Site	Skierniewice		Poland	96-100
294	Research Site	Sosnowiec		Poland	41-200
295	Research Site	Starachowice		Poland	27-200
296	Research Site	Szczecin		Poland	70-111
297	Research Site	Słupca		Poland	62-400
298	Research Site	Trzebnica		Poland	55-100
299	Research Site	Wrocław		Poland	51-162
300	Research Site	Wrocław		Poland	53-301
301	Research Site	Żnin		Poland	88-400
302	Research Site	Belgrade		Serbia	11000
303	Research Site	Celje		Slovenia	3000
304	Research Site	Golnik		Slovenia	4204
305	Research Site	Kamnik		Slovenia	1241
306	Research Site	Ljubljana		Slovenia	1000
307	Research Site	Maribor		Slovenia	2000
308	Research Site	Goteborg		Sweden	405 30
309	Research Site	Göteborg		Sweden	41345
310	Research Site	Helsingborg		Sweden	252 20
311	Research Site	Lund		Sweden	221 85
312	Research Site	Malmo		Sweden	21152
313	Research Site	Stockholm		Sweden	114 46
314	Research Site	Uppsala		Sweden	751 85
315	Research Site	Changhua		Taiwan	500
316	Research Site	Kaohsiung		Taiwan	83301
317	Research Site	Kaohsiung		Taiwan
318	Research Site	New-Taipei		Taiwan	22056
319	Research Site	Taichung		Taiwan	40447
320	Research Site	Taichung		Taiwan	40705
321	Research Site	Taipei		Taiwan	112
322	Research Site	Taipei		Taiwan
323	Research Site	Bangkoknoi		Thailand	10700
324	Research Site	Bangkok		Thailand	10600
325	Research Site	Hat Yai		Thailand	90110
326	Research Site	Khon Kaen		Thailand	40002
327	Research Site	Muang,		Thailand	55000
328	Research Site	Nonthaburi		Thailand	11000
329	Research Site	Adana		Turkey	01330
330	Research Site	Ankara		Turkey	06280
331	Research Site	Bursa		Turkey	16059
332	Research Site	Istanbul		Turkey	34020
333	Research Site	Istanbul		Turkey	34098
334	Research Site	İstanbul		Turkey	34844
335	Research Site	Izmir		Turkey	35100
336	Research Site	Izmir		Turkey	35110
337	Research Site	Mersin		Turkey	33343
338	Research Site	Cherkasy		Ukraine	18009
339	Research Site	Chernivtsi		Ukraine	58000
340	Research Site	Chernivtsi		Ukraine	58022
341	Research Site	Dnipropetrovsk		Ukraine	49051
342	Research Site	Ivano-Frankivsk		Ukraine	76012
343	Research Site	Kharkiv		Ukraine	61035
344	Research Site	Kharkiv		Ukraine	61039
345	Research Site	Kyiv		Ukraine	03680
346	Research Site	Kyiv		Ukraine	04107
347	Research Site	Lutsk		Ukraine	43000
348	Research Site	Lviv		Ukraine	79066
349	Research Site	Odesa		Ukraine	65025
350	Research Site	Vinnytsia		Ukraine	21001
351	Research Site	Zaporizhzhya		Ukraine	69063
352	Research Site	Zaporizhzhya		Ukraine	69065
353	Research Site	Zaporizhzhya		Ukraine	69068
354	Research Site	Can Tho		Vietnam	900000
355	Research Site	Hanoi		Vietnam	100000
356	Research Site	Ho Chi Minh		Vietnam	700000

Sponsors and Collaborators

AstraZeneca
MedImmune LLC

Investigators

Principal Investigator: Bartolome R. Celli, MD, Brigham and Women's Hospital, Pulmonary Division, 75 Francis Street, PBB Clinics 3, Boston, MA 02115

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.

Responsible Party:

AstraZeneca

ClinicalTrials.gov Identifier:

NCT02155660

Other Study ID Numbers:

D3251C00004

First Posted:

Jun 4, 2014

Last Update Posted:

Jun 26, 2019

Last Verified:

Jun 1, 2019

Keywords provided by AstraZeneca

Obstructive Lung Diseases

Chronic Obstructive Pulmonary Disease

Lung Disease

Bronchial Diseases

COPD Exacerbation

Respiratory Tract Diseases

Additional relevant MeSH terms:

Lung Diseases

Lung Diseases, Obstructive

Pulmonary Disease, Chronic Obstructive

Benralizumab

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	2255 patients signed informed consent and were randomized to received treatment with benralizumab 10 mg,30 mg, 100 mg or placebo. One participant was excluded from the analysis. Therefore results are provided for 2254 participants.

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Period Title: Overall Study
STARTED	562	562	562	568
COMPLETED	504	489	502	507
NOT COMPLETED	58	73	60	61

Baseline Characteristics

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo	Total
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Total of all reporting groups
Overall Participants	562	562	562	568	2254
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.7 (8.47)	65.6 (8.61)	65.0 (8.23)	65.3 (8.44)	65.2 (8.44)
Sex: Female, Male (Count of Participants)
Female	196 34.9%	194 34.5%	207 36.8%	209 36.8%	806 35.8%
Male	366 65.1%	368 65.5%	355 63.2%	359 63.2%	1448 64.2%
Race/Ethnicity, Customized (participants) [Number]
White	441 78.5%	444 79%	443 78.8%	446 78.5%	1774 78.7%
Black or African American	8 1.4%	12 2.1%	16 2.8%	19 3.3%	55 2.4%
Asian	70 12.5%	69 12.3%	67 11.9%	67 11.8%	273 12.1%
Other	43 7.7%	37 6.6%	36 6.4%	36 6.3%	152 6.7%

Outcome Measures

1. Primary Outcome

Title	Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL
Description	A COPD exacerbation is defined by symptomatic worsening of COPD requiring: Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or Use of antibiotics; and/or An inpatient hospitalization or death due to COPD Annual COPD exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.
Time Frame	Immediately following the first IP dose through week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	377	394	386	388
Least Squares Mean (95% Confidence Interval) [Exacerbations per year]	0.99	1.21	1.09	1.17

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 10 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0638
	Comments
	Method	Negative binomial
	Comments	Model includes treatment group, EOS cohort, region, background therapy, number of exacerbations in the previous year.

Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95% 0.71 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.6575
	Comments
	Method	Negative binomial
	Comments	Model includes treatment group, EOS cohort, region, background therapy, number of exacerbations in the previous year.

Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95% 0.88 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 100 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3988
	Comments
	Method	Negative binomial
	Comments	Model includes treatment group, EOS cohort, region, background therapy, number of exacerbations in the previous year.

Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95% 0.78 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS<220/uL
Description	A COPD exacerbation is defined by symptomatic worsening of COPD requiring: Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or Use of antibiotics; and/or An inpatient hospitalization or death due to COPD Annual COPD exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.
Time Frame	Immediately following the first IP dose through week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS<220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	185	168	176	180
Least Squares Mean (95% Confidence Interval) [Exacerbations per year]	1.23	1.27	1.21	1.18

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 10 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.7564
	Comments
	Method	Negative binomial
	Comments	Model includes treatment group, region, background therapy, number of exacerbations in the previous year.

Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95% 0.82 to 1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.5573
	Comments
	Method	Negative binomial
	Comments	Model includes treatment group, region, background therapy, number of exacerbations in the previous year.

Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95% 0.84 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 100 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8644
	Comments
	Method	Negative binomial
	Comments	Model includes treatment group, region, background therapy, number of exacerbations in the previous year.

Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95% 0.80 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline EOS>=220/uL
Description	Pre-bronchodilator FEV1 (L) is collected at Weeks 0, 4, 8, 16, 24, 32, 40, 48, and 56. Baseline is the last non-missing value with quality (acceptable or borderline quality grade) prior to the first dose of study treatment.
Time Frame	First IP up to end of treatment Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	325	322	347	344
Mean (Standard Deviation) [Liter]	0.021 (0.346)	0.011 (0.289)	0.033 (0.291)	0.016 (0.292)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 10 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.5043
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline FEV1 value, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.015
	Confidence Interval	(2-Sided) 95% -0.029 to 0.059
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.7691
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline FEV1 value, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.007
	Confidence Interval	(2-Sided) 95% -0.051 to 0.037
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 100 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3767
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline FEV1 value, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95% -0.024 to 0.064
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Mean Change From Baseline in SGRQ Total Score for Patients With Baseline EOS>=220/uL
Description	SGRQ is from 50-item PRO instrument. The SGRQ total score is expressed as a percentage of overall impairment, in which 100% means the worst possible health status and 0 indicates the best possible health status.
Time Frame	First IP up to Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	331	329	354	349
Mean (Standard Deviation) [Percentage]	-7.733 (14.996)	-8.674 (17.910)	-7.257 (15.989)	-6.863 (16.344)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 10 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3636
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline SGRQ score, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.011
	Confidence Interval	(2-Sided) 95% -3.192 to 1.171
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2106
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline SGRQ score, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.388
	Confidence Interval	(2-Sided) 95% -3.562 to 0.786
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 100 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.5851
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline SGRQ score, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.602
	Confidence Interval	(2-Sided) 95% -2.763 to 1.560
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Mean Change From Baseline in CAT Total Score for Patients With Baseline EOS>=220/uL
Description	CAT is an 8-item PRO developed to measure the impact of COPD on health status. The instrument uses semantic differential six-point response scales. A CAT total score is the sum of item responses. Score ranges from 0 to 40 with higher scores indicative of greater COPD impact on health status.
Time Frame	First IP up to Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	332	331	354	350
Mean (Standard Deviation) [Score on a scale]	-2.18 (6.78)	-2.43 (7.18)	-2.36 (6.67)	-2.36 (6.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 10 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8525
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline CAT total score, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95% -0.82 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.9870
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline CAT total score, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95% -0.91 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 100 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8204
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline CAT total score, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95% -1.00 to 0.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Mean Change From Baseline in E-RS: COPD Total Score for Patients With Baseline EOS>=220/uL
Description	The E-RS: COPD is an 11-item PRO developed to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS: COPD item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity.
Time Frame	First IP up to Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	316	302	317	325
Mean (Standard Deviation) [Score on a scale]	-1.657 (5.701)	-2.219 (6.381)	-1.593 (5.665)	-1.137 (5.935)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 10 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2636
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline total score, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95% -1.102 to 0.301
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4087
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline total score, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.296
	Confidence Interval	(2-Sided) 95% -0.998 to 0.406
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 100 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2336
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline total score, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.425
	Confidence Interval	(2-Sided) 95% -1.125 to 0.275
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Mean Change From Baseline in Total Rescue Medication Use (Number of Puffs Per Day) for Patients With Baseline EOS>=220/uL
Description	The number of rescue medication inhalations and nebulizer treatments taken are recorded by the patient in the eDiary twice daily. Total rescue medication use is the sum of daytime and night-time use.
Time Frame	First IP up to Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	305	290	310	314
Mean (Standard Deviation) [Puffs/day]	-0.36 (3.04)	-0.24 (3.36)	-0.17 (3.02)	0.23 (3.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 10 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline rescue med. use, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.642
	Confidence Interval	(2-Sided) 95% -1.029 to -0.254
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0852
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline rescue med. use, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.340
	Confidence Interval	(2-Sided) 95% -0.727 to 0.047
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 100 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0650
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline rescue med. use, EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.364
	Confidence Interval	(2-Sided) 95% -0.750 to 0.023
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Mean Change From Baseline in Proportion of Nights With Awakenings Due to Respiratory Symptoms for Patients With Baseline EOS>=220/uL
Description	Change from baseline to Week 56 in proportion of nights with awakenings due to respiratory symptoms.
Time Frame	First IP up to Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	316	298	321	322
Mean (Standard Deviation) [Proportion of nights]	-0.092 (0.297)	-0.131 (0.332)	-0.084 (0.334)	-0.053 (0.345)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 10 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0415
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline prop. of nights awakens., EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.041
	Confidence Interval	(2-Sided) 95% -0.081 to -0.002
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0069
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline prop. of nights awakens., EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.055
	Confidence Interval	(2-Sided) 95% -0.094 to -0.015
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 100 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2008
	Comments
	Method	Mixed Models Analysis
	Comments	Model includes treatment group, baseline prop. of nights awakens., EOS cohort, region, background therapy, visit, and treatment by visit interaction.

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.026
	Confidence Interval	(2-Sided) 95% -0.065 to 0.014
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants by Number of COPD Exacerbations Based on EXACT-PRO for Patients With Baseline EOS>=220/uL
Description	The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while considering their experiences "today". The daily EXACT-PRO total score is recorded and has a range of 0-100 with higher scores indicative of greater severity. COPD exacerbation event frequency is calculated based on comparison of the baseline score with daily total scores. An increase of EXACT-PRO total score ≥9 for 3 days or ≥12 for 2 days indicates a COPD exacerbation event has occurred.
Time Frame	Immediately following first IP up to week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	377	394	385	388
0	166 29.5%	173 30.8%	162 28.8%	159 28%
1	108 19.2%	107 19%	113 20.1%	119 21%
2	45 8%	51 9.1%	56 10%	46 8.1%
3	21 3.7%	27 4.8%	25 4.4%	27 4.8%
4	14 2.5%	16 2.8%	13 2.3%	13 2.3%
5	8 1.4%	8 1.4%	9 1.6%	12 2.1%
6	7 1.2%	6 1.1%	4 0.7%	7 1.2%
7	2 0.4%	4 0.7%	1 0.2%	2 0.4%
8	4 0.7%	1 0.2%	2 0.4%	1 0.2%
9	0 0%	1 0.2%	0 0%	1 0.2%
10	2 0.4%	0 0%	0 0%	0 0%
11	0 0%	0 0%	0 0%	1 0.2%

10. Secondary Outcome

Title	Severity of EXACT-PRO for Patients With Baseline EOS>=220/uL
Description	The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while considering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. Severity of the study is the highest score of EXACT-PRO.
Time Frame	Immediately following first IP up to week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	211	221	223	229
Mean (Standard Deviation) [Score on a scale]	50.3 (12.30)	52.1 (11.3)	51.2 (11.0)	51.0 (11.7)

11. Secondary Outcome

Title	Duration of COPD Exacerbation Based on EXACT-PRO Score for Patients With Baseline EOS>=220/uL
Description	The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while considering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. COPD exacerbation event frequency is identified by comparing the baseline score with daily total scores. An increase in EXACT-PRO total score ≥9 for 3 days or ≥12 for 2 days indicate an event has occurred. Event duration is calculated after identification of the following five parameters: 1) onset; 2) three-day rolling average; 3) maximum observed value; 4) threshold for improvement; and 5) recovery. That is, duration of the exacerbation is the time elapse between onset and recovery of the event.
Time Frame	Immediately following first IP up to week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	211	221	223	229
Mean (Standard Deviation) [Days]	110.1 (114.0)	96.1 (109.3)	99.8 (114.8)	99.9 (113.9)

12. Secondary Outcome

Title	Annual EXACT-PRO Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL
Description	The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while considering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. Event frequency is calculated by comparing the baseline with daily total scores. An increase in EXACT-PRO total score ≥9 for 3 days or ≥12 for 2 days indicate an event has occurred. Annual EXACT-PRO exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.
Time Frame	Immediately following the first IP dose through week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	377	394	385	388
Least Squares Mean (95% Confidence Interval) [Exacerbations per year]	1.20	1.21	1.13	1.23

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 10 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8158
	Comments
	Method	Negative binomial
	Comments	Model includes treatment group, EOS cohort, region, background therapy, number of exacerbations in the previous year.

Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95% 0.81 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8378
	Comments
	Method	Negative binomial
	Comments	Model includes treatment group, EOS cohort, region, background therapy, number of exacerbations in the previous year.

Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95% 0.82 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 100 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3759
	Comments
	Method	Negative binomial
	Comments	Model includes treatment group, EOS cohort, region, background therapy, number of exacerbations in the previous year.

Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95% 0.76 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Number of Participants Having at Least 1 COPD Exacerbation for Patients With Baseline EOS>=220/uL
Description	A COPD exacerbation is defined by symptomatic worsening COPD requiring systemic corticosteroids, antibiotics, or an inpatient hospitalization/death due to COPD.
Time Frame	Immediately following first IP dose up to week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	377	394	386	388
Count of Participants [Participants]	203 36.1%	241 42.9%	214 38.1%	208 36.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 10 mg, Placebo
	Comments	Proportion of participants with >=1 COPD exacerbation.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.9141
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test controlling for EOS cohort, region, and background therapy.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95% 0.76 to 1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30 mg, Placebo
	Comments	Proportion of participants with >=1 COPD exacerbation.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0323
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test controlling for EOS cohort, region, and background therapy.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.39
	Confidence Interval	(2-Sided) 95% 1.03 to 1.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 100 mg, Placebo
	Comments	Proportion of participants with >=1 COPD exacerbation.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.5109
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	CMH test controlling for EOS cohort, region, and background therapy.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95% 0.82 to 1.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Time to First COPD Exacerbation
Description	Time to first COPD exacerbation is from the randomization date to the first occurrence of COPD exacerbation.
Time Frame	Immediately following IP dose to Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	377	394	386	388
Median (95% Confidence Interval) [Days]	315	260	322	337

15. Secondary Outcome

Title	Annual COPD Exacerbation Rate Associated With ER or Hospitalization Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL
Description	Annual COPD exacerbations rate that result in ER or hospitalization is calculated by number of exacerbations resulting ER or hospitalization divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.
Time Frame	Immediately following the first IP dose through week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	377	394	386	388
Least Squares Mean (95% Confidence Interval) [Exacerbations per year]	0.22	0.29	0.22	0.32

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 10 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0287
	Comments
	Method	Negative binomial
	Comments	Model includes treatment group, EOS cohort, region, background therapy, previous year exacerbations associated with hospitalization (Y/N).

Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95% 0.49 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4631
	Comments
	Method	Negative binomial
	Comments	Model includes treatment group, EOS cohort, region, background therapy, previous year exacerbations associated with hospitalization (Y/N).

Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95% 0.65 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 100 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0185
	Comments
	Method	Negative binomial
	Comments	Model includes treatment group, EOS cohort, region, background therapy, previous year exacerbations associated with hospitalization (Y/N).

Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95% 0.48 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Number of Participants Had COPD-related Healthcare Encounter for Patient With Baseline EOS>=220/uL
Description	Types of healthcare encounter: Hospitalisations (inc. intensive care and/or general care), Emergency department visits, Unscheduled outpatients visits, Home visits, Telephone calls, and ambulance transports.
Time Frame	Immediately following first IP dose up to Week 56

Outcome Measure Data

Analysis Population Description
Full analysis set, baseline EOS>=220/uL

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	377	394	386	388
Hospitalisations	45 8%	67 11.9%	48 8.5%	59 10.4%
Emergency department	49 8.7%	72 12.8%	58 10.3%	71 12.5%
Unscheduled outpatient visits	208 37%	230 40.9%	225 40%	211 37.1%
Home visits	14 2.5%	20 3.6%	17 3%	14 2.5%
Telephone calls	98 17.4%	112 19.9%	109 19.4%	114 20.1%
Ambulance transports	10 1.8%	19 3.4%	20 3.6%	22 3.9%

17. Secondary Outcome

Title	Duration of Study Treatment Administration
Description	Duration of study treatment is calculated from first dose date to last dose date + 1 day.
Time Frame	From first dose date to last dose date, 48 weeks per protocol.

Outcome Measure Data

Analysis Population Description
Safety analysis set

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	561	563	562	568
Mean (Standard Deviation) [Days]	307.4 (80.38)	302.2 (84.62)	303.0 (88.48)	308.8 (78.95)

18. Secondary Outcome

Title	Serum Concentration of Benralizumab
Description	PK serum samples were collected pre-dose at each visit.
Time Frame	Pre-first dose and pre-dose at end of treatment (week 56).

Outcome Measure Data

Analysis Population Description
PK analysis set

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	558	560	552
Baseline	NA (NA)	NA (NA)	NA (51.95)
Week 56	42.51 (384.81)	222.92 (248.24)	594.33 (321.66)

19. Secondary Outcome

Title	Immunogenicity of Benralizumab
Description	Anti-drug antibody (ADA) responses such as ADA prevalence, ADA incidence, ADA persistently positive counts, etc. were presented.
Time Frame	Pre-treatment until end of follow-up, week 60 per protocol.

Outcome Measure Data

Analysis Population Description
Safety analysis set. For each parameter, the number of subjects at risk is to be analyzed.

Arm/Group Title	Benralizumab 10 mg	Benralizumab 30 mg	Benralizumab 100 mg	Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously	Every 8 weeks administered subcutaneously
Measure Participants	561	563	562	568
ADA prevalence	70 12.5%	52 9.3%	77 13.7%	26 4.6%
ADA incidence	60 10.7%	39 6.9%	65 11.6%	16 2.8%
Both base/post-baseline positive	9 1.6%	8 1.4%	5 0.9%	10 1.8%
Only post baseline	57 10.1%	38 6.8%	64 11.4%	14 2.5%
Only baseline	4 0.7%	6 1.1%	8 1.4%	2 0.4%
ADA persistently positive	42 7.5%	30 5.3%	43 7.7%	6 1.1%
ADA transiently positive	15 2.7%	8 1.4%	21 3.7%	8 1.4%
nAb prevalence	55 9.8%	37 6.6%	59 10.5%	13 2.3%
nAb incidence	50 8.9%	33 5.9%	52 9.3%	9 1.6%

Adverse Events

	Benra 10 mg		Benra 30 mg		Benra 100 mg		Placebo
Time Frame	From the time patient signed informed consent throughout the treatment period to the follow-up visit (week 60).
Adverse Event Reporting Description	Adverse events are presented according to the actual treatment the participants received. One participant randomized to Benra 10 mg was treated with Benra 30 mg, thus this participant is counted in Benra 30 mg group, and hence one less participant in Benra 10 mg, compared with patient flow summary (where participants are summarized per randomized treatment group).

Arm/Group Title	Benra 10 mg		Benra 30 mg		Benra 100 mg		Placebo
Arm/Group Description	Every 8 weeks administered subcutaneously		Every 8 weeks administered subcutaneously		Every 8 weeks administered subcutaneously		Every 8 weeks administered subcutaneously
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/561 (3%)		21/563 (3.7%)		17/562 (3%)		19/568 (3.3%)
Serious Adverse Events
	Benra 10 mg		Benra 30 mg		Benra 100 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	144/561 (25.7%)		177/563 (31.4%)		127/562 (22.6%)		158/568 (27.8%)
Blood and lymphatic system disorders
Anaemia	0/561 (0%)	0	2/563 (0.4%)	2	0/562 (0%)	0	1/568 (0.2%)	1
Disseminated intravascular coagulation	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Haemorrhagic anaemia	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Iron deficiency anaemia	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Polycythaemia	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	2
Cardiac disorders
Acute coronary syndrome	1/561 (0.2%)	1	1/563 (0.2%)	1	1/562 (0.2%)	1	3/568 (0.5%)	3
Acute myocardial infarction	2/561 (0.4%)	2	7/563 (1.2%)	7	1/562 (0.2%)	1	1/568 (0.2%)	1
Angina pectoris	2/561 (0.4%)	3	1/563 (0.2%)	1	1/562 (0.2%)	1	2/568 (0.4%)	2
Angina unstable	3/561 (0.5%)	3	2/563 (0.4%)	2	1/562 (0.2%)	1	1/568 (0.2%)	1
Aortic valve incompetence	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Atrial fibrillation	2/561 (0.4%)	2	1/563 (0.2%)	3	1/562 (0.2%)	1	1/568 (0.2%)	1
Atrial flutter	1/561 (0.2%)	1	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Atrioventricular block	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Cardiac failure	0/561 (0%)	0	2/563 (0.4%)	2	3/562 (0.5%)	3	2/568 (0.4%)	3
Cardiac failure acute	2/561 (0.4%)	2	0/563 (0%)	0	1/562 (0.2%)	1	1/568 (0.2%)	1
Cardiac failure chronic	1/561 (0.2%)	1	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Cardiac failure congestive	3/561 (0.5%)	3	2/563 (0.4%)	3	4/562 (0.7%)	5	4/568 (0.7%)	4
Cardio-respiratory arrest	1/561 (0.2%)	1	1/563 (0.2%)	1	1/562 (0.2%)	1	0/568 (0%)	0
Cor pulmonale	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Coronary artery disease	1/561 (0.2%)	1	1/563 (0.2%)	1	0/562 (0%)	0	1/568 (0.2%)	1
Myocardial infarction	3/561 (0.5%)	3	1/563 (0.2%)	1	3/562 (0.5%)	3	1/568 (0.2%)	1
Right ventricular failure	0/561 (0%)	0	2/563 (0.4%)	2	0/562 (0%)	0	2/568 (0.4%)	2
Sinus tachycardia	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Tachycardia	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Ventricular extrasystoles	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Ventricular fibrillation	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Ear and labyrinth disorders
Vertigo positional	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Eye disorders
Retinal artery embolism	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Gastrointestinal disorders
Abdominal incarcerated hernia	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Abdominal pain	2/561 (0.4%)	2	0/563 (0%)	0	0/562 (0%)	0	2/568 (0.4%)	3
Chronic gastritis	0/561 (0%)	0	1/563 (0.2%)	1	1/562 (0.2%)	1	0/568 (0%)	0
Colitis	0/561 (0%)	0	2/563 (0.4%)	2	0/562 (0%)	0	0/568 (0%)	0
Colitis ulcerative	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Colonic pseudo-obstruction	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Constipation	1/561 (0.2%)	2	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Diarrhoea	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Diverticular perforation	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Diverticulum	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Diverticulum intestinal	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Duodenitis	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Femoral hernia strangulated	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Gastric ulcer	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Gastritis	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Gastrointestinal haemorrhage	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Gastrointestinal polyp haemorrhage	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Haematochezia	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Ileus	1/561 (0.2%)	1	0/563 (0%)	0	1/562 (0.2%)	2	0/568 (0%)	0
Incarcerated inguinal hernia	0/561 (0%)	0	2/563 (0.4%)	2	0/562 (0%)	0	0/568 (0%)	0
Inguinal hernia	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Intestinal obstruction	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Intestinal perforation	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Large intestine perforation	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	1/568 (0.2%)	1
Lower gastrointestinal haemorrhage	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Lumbar hernia	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Melaena	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Oesophageal hypomotility	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Small intestinal obstruction	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Vomiting	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
General disorders
Chest pain	1/561 (0.2%)	1	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Death	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Multiple organ dysfunction syndrome	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	1/568 (0.2%)	1
Oedema	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Hepatobiliary disorders
Bile duct stone	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Cholecystitis	0/561 (0%)	0	2/563 (0.4%)	2	0/562 (0%)	0	1/568 (0.2%)	1
Cholecystitis acute	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Cholecystitis chronic	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Cholelithiasis	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	1/568 (0.2%)	1
Immune system disorders
Drug hypersensitivity	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Food allergy	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Hypersensitivity	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Infections and infestations
Abdominal abscess	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Acute sinusitis	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Appendicitis	1/561 (0.2%)	1	2/563 (0.4%)	2	1/562 (0.2%)	1	1/568 (0.2%)	1
Bronchitis	0/561 (0%)	0	4/563 (0.7%)	4	1/562 (0.2%)	1	3/568 (0.5%)	3
Bronchitis bacterial	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Bursitis infective	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Catheter site cellulitis	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Cellulitis	2/561 (0.4%)	2	2/563 (0.4%)	2	0/562 (0%)	0	1/568 (0.2%)	1
Clostridium difficile colitis	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Cystitis	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Diarrhoea infectious	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Diverticulitis	1/561 (0.2%)	1	1/563 (0.2%)	1	1/562 (0.2%)	1	1/568 (0.2%)	1
Erysipelas	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Gastroenteritis viral	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	1/568 (0.2%)	1
Hepatitis C	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Herpes zoster	0/561 (0%)	0	0/563 (0%)	0	2/562 (0.4%)	2	1/568 (0.2%)	1
Infectious colitis	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Influenza	1/561 (0.2%)	1	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Intestinal sepsis	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Labyrinthitis	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Laryngitis	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Localised infection	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Lower respiratory tract infection	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Lung abscess	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Lung infection	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Osteomyelitis	0/561 (0%)	0	0/563 (0%)	0	2/562 (0.4%)	2	0/568 (0%)	0
Peritonitis	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Pneumonia	19/561 (3.4%)	20	22/563 (3.9%)	25	9/562 (1.6%)	10	30/568 (5.3%)	34
Pneumonia bacterial	5/561 (0.9%)	5	5/563 (0.9%)	7	2/562 (0.4%)	2	1/568 (0.2%)	1
Pneumonia mycoplasmal	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Post procedural infection	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Postoperative wound infection	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Pseudomembranous colitis	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Pseudomonas bronchitis	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Pulmonary sepsis	0/561 (0%)	0	2/563 (0.4%)	2	1/562 (0.2%)	1	0/568 (0%)	0
Pulmonary tuberculosis	1/561 (0.2%)	1	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Septic shock	3/561 (0.5%)	3	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Sinusitis	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Tracheobronchitis	1/561 (0.2%)	1	1/563 (0.2%)	1	0/562 (0%)	0	1/568 (0.2%)	1
Tuberculosis	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Upper respiratory tract infection	1/561 (0.2%)	1	1/563 (0.2%)	1	1/562 (0.2%)	1	4/568 (0.7%)	4
Urinary tract infection	1/561 (0.2%)	1	2/563 (0.4%)	4	0/562 (0%)	0	1/568 (0.2%)	1
Urosepsis	1/561 (0.2%)	1	0/563 (0%)	0	1/562 (0.2%)	1	1/568 (0.2%)	1
Viral upper respiratory tract infection	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Injury, poisoning and procedural complications
Abdominal injury	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Anaemia postoperative	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Ankle fracture	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Carbon monoxide poisoning	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Concussion	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Femoral neck fracture	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	1/568 (0.2%)	1
Femur fracture	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Foot fracture	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Forearm fracture	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Hand fracture	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Hip fracture	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Humerus fracture	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Laceration	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Lumbar vertebral fracture	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Open fracture	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Procedural pain	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Rib fracture	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Road traffic accident	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Subdural haematoma	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	1/568 (0.2%)	1
Tibia fracture	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Toxicity to various agents	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Traumatic fracture	1/561 (0.2%)	1	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Traumatic haemorrhage	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Investigations
Anticoagulation drug level above therapeutic	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Aspartate aminotransferase increased	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Electrocardiogram T wave inversion	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
False positive tuberculosis test	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Hepatic enzyme increased	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
International normalised ratio increased	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Oxygen saturation decreased	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Metabolism and nutrition disorders
Alcohol intolerance	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Cachexia	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Diabetes mellitus	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Hyperglycaemia	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	2/568 (0.4%)	2
Hyperkalaemia	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Hypoglycaemia	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Hyponatraemia	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Malnutrition	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Musculoskeletal and connective tissue disorders
Bursitis	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Lumbar spinal stenosis	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Musculoskeletal chest pain	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Osteoarthritis	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	1/568 (0.2%)	1
Psoriatic arthropathy	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Spondylolisthesis	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Trigger finger	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Abdominal neoplasm	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Acute myeloid leukaemia	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Adenocarcinoma gastric	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Adenocarcinoma of colon	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	1/568 (0.2%)	1
Basal cell carcinoma	1/561 (0.2%)	1	1/563 (0.2%)	1	1/562 (0.2%)	1	1/568 (0.2%)	1
Bladder cancer	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Brain cancer metastatic	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Brain neoplasm benign	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Breast cancer female	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Colon adenoma	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Colorectal cancer metastatic	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Follicular thyroid cancer	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Laryngeal squamous cell carcinoma	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Lip and/or oral cavity cancer	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Lung adenocarcinoma	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Lung cancer metastatic	1/561 (0.2%)	1	1/563 (0.2%)	1	0/562 (0%)	0	2/568 (0.4%)	2
Lung neoplasm malignant	0/561 (0%)	0	2/563 (0.4%)	2	1/562 (0.2%)	1	0/568 (0%)	0
Metastases to central nervous system	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Metastatic malignant melanoma	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Neuroendocrine carcinoma metastatic	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	1/568 (0.2%)	1
Oesophageal adenocarcinoma stage 0	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Pancreatic carcinoma	0/561 (0%)	0	2/563 (0.4%)	2	0/562 (0%)	0	0/568 (0%)	0
Pancreatic carcinoma metastatic	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Polycythaemia vera	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Prostate cancer	1/561 (0.2%)	1	0/563 (0%)	0	2/562 (0.4%)	2	0/568 (0%)	0
Renal cell carcinoma	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Renal neoplasm	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Squamous cell carcinoma of lung	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Squamous cell carcinoma of the cervix	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Sweat gland tumour	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Thyroid cancer	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Transitional cell cancer of the renal pelvis and ureter	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Nervous system disorders
Carotid arteriosclerosis	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Cerebellar haemorrhage	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Cerebrovascular accident	1/561 (0.2%)	1	4/563 (0.7%)	4	1/562 (0.2%)	1	1/568 (0.2%)	1
Cervical myelopathy	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Cognitive disorder	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Dementia Alzheimer's type	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Dizziness	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Encephalopathy	0/561 (0%)	0	0/563 (0%)	0	2/562 (0.4%)	2	0/568 (0%)	0
Haemorrhage intracranial	0/561 (0%)	0	1/563 (0.2%)	1	1/562 (0.2%)	1	0/568 (0%)	0
Haemorrhagic stroke	0/561 (0%)	0	0/563 (0%)	0	2/562 (0.4%)	2	0/568 (0%)	0
Hepatic encephalopathy	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Intercostal neuralgia	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Intracranial aneurysm	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Ischaemic stroke	1/561 (0.2%)	1	1/563 (0.2%)	1	1/562 (0.2%)	3	2/568 (0.4%)	2
Lumbosacral radiculopathy	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Multiple sclerosis relapse	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Myoclonus	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	2
Seizure	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Syncope	2/561 (0.4%)	2	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Thrombotic cerebral infarction	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Transient ischaemic attack	2/561 (0.4%)	2	1/563 (0.2%)	1	1/562 (0.2%)	1	1/568 (0.2%)	1
Vertebrobasilar insufficiency	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Psychiatric disorders
Alcohol abuse	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Alcoholism	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Anxiety	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	1/568 (0.2%)	1
Bipolar disorder	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Delirium	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Depression	2/561 (0.4%)	2	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Major depression	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Post-traumatic stress disorder	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Renal and urinary disorders
Acute kidney injury	4/561 (0.7%)	4	0/563 (0%)	0	2/562 (0.4%)	2	3/568 (0.5%)	3
Chronic kidney disease	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	1/568 (0.2%)	1
Hydronephrosis	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Nephrolithiasis	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	1/568 (0.2%)	1
Renal failure	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	1/568 (0.2%)	1
Renal infarct	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Ureterolithiasis	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Reproductive system and breast disorders
Acquired hydrocele	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Benign prostatic hyperplasia	1/561 (0.2%)	1	1/563 (0.2%)	1	2/562 (0.4%)	2	1/568 (0.2%)	1
Pelvic prolapse	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Prostatitis	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Acute respiratory failure	3/561 (0.5%)	3	1/563 (0.2%)	1	4/562 (0.7%)	4	5/568 (0.9%)	5
Aspiration	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Atelectasis	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Chronic obstructive pulmonary disease	92/561 (16.4%)	129	107/563 (19%)	136	80/562 (14.2%)	106	89/568 (15.7%)	140
Chronic respiratory failure	1/561 (0.2%)	1	0/563 (0%)	0	2/562 (0.4%)	3	1/568 (0.2%)	1
Cystic lung disease	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Dyspnoea	3/561 (0.5%)	3	1/563 (0.2%)	1	0/562 (0%)	0	1/568 (0.2%)	1
Hypercapnia	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Hypoxia	1/561 (0.2%)	1	1/563 (0.2%)	1	0/562 (0%)	0	1/568 (0.2%)	1
Lung disorder	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Lung infiltration	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Pleural effusion	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	1/568 (0.2%)	1
Pneumonia aspiration	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	2/568 (0.4%)	2
Pneumothorax	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	2/568 (0.4%)	2
Pneumothorax spontaneous	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Pulmonary embolism	6/561 (1.1%)	6	0/563 (0%)	0	3/562 (0.5%)	3	0/568 (0%)	0
Pulmonary mass	0/561 (0%)	0	2/563 (0.4%)	2	0/562 (0%)	0	1/568 (0.2%)	1
Pulmonary oedema	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Respiratory failure	3/561 (0.5%)	3	2/563 (0.4%)	2	1/562 (0.2%)	1	1/568 (0.2%)	2
Skin and subcutaneous tissue disorders
Angioedema	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Eczema	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	0/568 (0%)	0
Henoch-Schonlein purpura	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Psoriasis	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Vascular disorders
Accelerated hypertension	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Aortic aneurysm	1/561 (0.2%)	1	1/563 (0.2%)	1	1/562 (0.2%)	1	1/568 (0.2%)	1
Aortic dissection	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	1/568 (0.2%)	1
Aortic stenosis	0/561 (0%)	0	1/563 (0.2%)	1	1/562 (0.2%)	1	0/568 (0%)	0
Arteriosclerosis	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Circulatory collapse	1/561 (0.2%)	1	0/563 (0%)	0	0/562 (0%)	0	0/568 (0%)	0
Deep vein thrombosis	0/561 (0%)	0	1/563 (0.2%)	1	0/562 (0%)	0	1/568 (0.2%)	1
Haematoma	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Hypertension	0/561 (0%)	0	0/563 (0%)	0	2/562 (0.4%)	2	0/568 (0%)	0
Hypertensive crisis	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	2/568 (0.4%)	2
Hypotension	0/561 (0%)	0	1/563 (0.2%)	2	0/562 (0%)	0	0/568 (0%)	0
Hypovolaemic shock	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Orthostatic hypotension	0/561 (0%)	0	0/563 (0%)	0	1/562 (0.2%)	1	0/568 (0%)	0
Penetrating aortic ulcer	0/561 (0%)	0	0/563 (0%)	0	0/562 (0%)	0	1/568 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Benra 10 mg		Benra 30 mg		Benra 100 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	251/561 (44.7%)		233/563 (41.4%)		238/562 (42.3%)		260/568 (45.8%)
General disorders
Oedema peripheral	15/561 (2.7%)	17	9/563 (1.6%)	9	17/562 (3%)	18	9/568 (1.6%)	10
Infections and infestations
Bronchitis	66/561 (11.8%)	94	70/563 (12.4%)	100	63/562 (11.2%)	87	66/568 (11.6%)	88
Influenza	11/561 (2%)	11	20/563 (3.6%)	22	15/562 (2.7%)	15	11/568 (1.9%)	12
Lower respiratory tract infection	26/561 (4.6%)	27	22/563 (3.9%)	29	15/562 (2.7%)	16	21/568 (3.7%)	27
Oral candidiasis	21/561 (3.7%)	25	12/563 (2.1%)	13	15/562 (2.7%)	20	12/568 (2.1%)	17
Sinusitis	15/561 (2.7%)	18	13/563 (2.3%)	19	15/562 (2.7%)	21	20/568 (3.5%)	24
Upper respiratory tract infection	68/561 (12.1%)	109	71/563 (12.6%)	98	67/562 (11.9%)	92	65/568 (11.4%)	89
Urinary tract infection	24/561 (4.3%)	34	24/563 (4.3%)	26	28/562 (5%)	32	18/568 (3.2%)	22
Viral upper respiratory tract infection	61/561 (10.9%)	73	47/563 (8.3%)	68	60/562 (10.7%)	92	70/568 (12.3%)	93
Musculoskeletal and connective tissue disorders
Back pain	11/561 (2%)	11	12/563 (2.1%)	12	17/562 (3%)	20	15/568 (2.6%)	15
Nervous system disorders
Headache	19/561 (3.4%)	20	16/563 (2.8%)	17	27/562 (4.8%)	34	24/568 (4.2%)	36
Respiratory, thoracic and mediastinal disorders
Dyspnoea	8/561 (1.4%)	10	10/563 (1.8%)	13	20/562 (3.6%)	24	24/568 (4.2%)	34
Vascular disorders
Hypertension	17/561 (3%)	22	16/563 (2.8%)	17	12/562 (2.1%)	12	21/568 (3.7%)	22

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT 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.

Results Point of Contact

Name/Title	Ulbaldo Martin
Organization	AstraZeneca
Phone	1.301.398.0163
Email	ulbaldo.martin@astrazeneca.com

Responsible Party:

AstraZeneca

ClinicalTrials.gov Identifier:

NCT02155660

Other Study ID Numbers:

D3251C00004

First Posted:

Jun 4, 2014

Last Update Posted:

Jun 26, 2019

Last Verified:

Jun 1, 2019

TERRANOVA: Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With Exacerbation History

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Exclusion criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Additional Information:

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

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Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

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Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

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Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

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Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

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Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

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Outcome Measure Data

Outcome Measure Data

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Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events