Trial Outcomes & Findings for A Safety Extension Study With Benralizumab for Asthmatic Adults on Inhaled Corticosteroid Plus Long-acting β2 Agonist (NCT NCT02808819)

NCT ID: NCT02808819

Last Updated: 2021-04-13

Results Overview

Change from baseline in hematologic lab parameter of Basophils.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

447 participants

Primary outcome timeframe

From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Results posted on

2021-04-13

Participant Flow

447 patients enrolled in MELTEMI, 1 patient from Czech Republic was not treated, thus 446 patients received at least 1 dose of IP. Among these treated participants, 347 were from studies SIROCCO(NCT01928771)/CALIMA(NCT01914757) and 99 were from study ZONDA(NCT02075255).

170 participants from SIROCCO(NCT01928771)/CALIMA(NCT01914757) assigned to Benralizumab 30 mg every 4 weeks (q4w) with 1 participant not treated. 178 participants from SIROCCO/CALIMA received Benralizumab every 8 weeks (q8w). 51 participants from ZONDA(NCT02075255) received Benralizumab q4w. 48 participants from study ZONDA received Benralizumab q8w.

Participant milestones

Participant milestones
Measure	Benra 30 mg q.4 Weeks Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks Benralizumab administered subcutaneously every 8 weeks
Overall Study STARTED	220	226
Overall Study Treated	220	226
Overall Study COMPLETED	189	195
Overall Study NOT COMPLETED	31	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Benra 30 mg q.4 Weeks Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks Benralizumab administered subcutaneously every 8 weeks
Overall Study eg. no treatment efficacy on asthma	5	4
Overall Study Withdrawal by Subject	10	13
Overall Study Site terminated by sponsor	2	0
Overall Study Pregnancy	1	0
Overall Study Lost to Follow-up	1	6
Overall Study Protocol Violation	0	1
Overall Study Development of study-specific withdrawal criteria	8	3
Overall Study Death	1	0
Overall Study Adverse Event	3	4

Baseline Characteristics

A Safety Extension Study With Benralizumab for Asthmatic Adults on Inhaled Corticosteroid Plus Long-acting β2 Agonist

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Benra 30 mg q.4 Weeks n=220 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=226 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=446 Participants Total of all reporting groups
Age, Continuous	53.5 Years STANDARD_DEVIATION 12.00 • n=5 Participants	53.0 Years STANDARD_DEVIATION 11.64 • n=7 Participants	53.2 Years STANDARD_DEVIATION 11.81 • n=5 Participants
Sex: Female, Male Female	140 Participants n=5 Participants	144 Participants n=7 Participants	284 Participants n=5 Participants
Sex: Female, Male Male	80 Participants n=5 Participants	82 Participants n=7 Participants	162 Participants n=5 Participants
Race/Ethnicity, Customized White	204 Participants n=5 Participants	206 Participants n=7 Participants	410 Participants n=5 Participants
Race/Ethnicity, Customized Black or African	9 Participants n=5 Participants	13 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized American Asian	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Population: Full analysis set. For each lab test, number of patients is the number of patients with available change from baseline value.

Change from baseline in hematologic lab parameter of Basophils.

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=173 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=178 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=351 Participants sum per row
Change From Baseline in Basophils, Full Analysis Set	0.014 10^9 cells/L Standard Deviation 0.0229	0.012 10^9 cells/L Standard Deviation 0.0243	0.013 10^9 cells/L Standard Deviation 0.0236

PRIMARY outcome

Timeframe: From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Population: Full analysis set. For each lab test, number of patients is the number of patients with available change from baseline value.

Change from baseline in hematologic lab parameter of Leukocytes.

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=178 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=182 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=360 Participants sum per row
Change From Baseline in Leukocytes, Full Analysis Set	-0.254 10^9 cells/L Standard Deviation 2.0446	-0.498 10^9 cells/L Standard Deviation 1.7217	-0.377 10^9 cells/L Standard Deviation 1.8896

PRIMARY outcome

Timeframe: From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Population: Full analysis set. For each lab test, number of patients is the number of patients with available change from baseline value.

Change from baseline in hematologic lab parameter of Lymphocytes.

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=173 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=178 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=351 Participants sum per row
Change From Baseline in Lymphocytes, Full Analysis Set	-0.098 10^9 cells/L Standard Deviation 0.5479	-0.142 10^9 cells/L Standard Deviation 0.6544	-0.121 10^9 cells/L Standard Deviation 0.6038

PRIMARY outcome

Timeframe: From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Population: Full analysis set. For each lab test, number of patients is the number of patients with available change from baseline value.

Change from baseline in hematologic lab parameter of Neutrophils.

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=173 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=178 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=351 Participants sum per row
Change From Baseline in Neutrophils, Full Analysis Set	-0.237 10^9 cells/L Standard Deviation 1.8765	-0.392 10^9 cells/L Standard Deviation 1.4802	-0.315 10^9 cells/L Standard Deviation 1.6866

PRIMARY outcome

Timeframe: From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Population: Full analysis set. For each lab test, number of patients is the number of patients with available change from baseline value.

Change from baseline in hematologic lab parameter of Monocytes.

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=173 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=179 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=352 Participants sum per row
Change From Baseline in Monocytes, Full Analysis Set	0.055 10^9 cells/L Standard Deviation 0.1835	0.056 10^9 cells/L Standard Deviation 0.1766	0.055 10^9 cells/L Standard Deviation 0.1798

PRIMARY outcome

Timeframe: From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Population: Full analysis set. For each lab test, number of patients is the number of patients with available change from baseline value.

Change from baseline in hematologic lab parameter of Platelets.

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=177 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=179 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=356 Participants sum per row
Change From Baseline in Platelets, Full Analysis Set	9.1 10^9 cells/L Standard Deviation 41.72	11.9 10^9 cells/L Standard Deviation 36.13	10.5 10^9 cells/L Standard Deviation 38.98

PRIMARY outcome

Timeframe: From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Population: Full analysis set. For each lab test, number of patients is the number of patients with available change from baseline value.

Change from baseline in hematologic lab parameter of Hematocrit.

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=172 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=177 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=349 Participants sum per row
Change From Baseline in Hematocrit, Full Analysis Set	-0.002 [ratio] Standard Deviation 0.0269	-0.003 [ratio] Standard Deviation 0.0260	-0.003 [ratio] Standard Deviation 0.0264

PRIMARY outcome

Timeframe: From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Population: Full analysis set. For each lab test, number of patients is the number of patients with available change from baseline value.

Change from baseline in hematologic lab parameter of Erythrocytes.

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=178 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=183 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=361 Participants sum per row
Change From Baseline in Erythrocytes, Full Analysis Set	-0.008 10^12 cells/L Standard Deviation 0.2922	-0.054 10^12 cells/L Standard Deviation 0.2614	-0.031 10^12 cells/L Standard Deviation 0.2776

PRIMARY outcome

Timeframe: From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Population: Full analysis set. For each lab test, number of patients is the number of patients with available change from baseline value.

Change from baseline in hematologic lab parameter of Hemoglobin.

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=178 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=183 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=361 Participants sum per row
Change From Baseline in Hemoglobin, Full Analysis Set	2.6 g/L Standard Deviation 8.92	1.2 g/L Standard Deviation 8.37	1.9 g/L Standard Deviation 8.66

PRIMARY outcome

Timeframe: From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Population: Full analysis set. For each lab test, number of patients is the number of patients with available change from baseline value.

Change from baseline in chemistry test ALT.

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=174 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=175 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=349 Participants sum per row
Change From Baseline in Alanine Aminotransferase (ALT), Full Analysis Set	0.007 ukat/L Standard Deviation 0.2060	0.004 ukat/L Standard Deviation 0.2118	0.005 ukat/L Standard Deviation 0.2086

PRIMARY outcome

Timeframe: From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Population: Full analysis set. For each lab test, number of patients is the number of patients with available change from baseline value.

Change from baseline in chemistry test AST.

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=174 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=175 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=349 Participants sum per row
Change From Baseline in Aspartate Aminotransferase (AST), Full Analysis Set	-0.021 ukat/L Standard Deviation 0.1258	-0.018 ukat/L Standard Deviation 0.1280	-0.020 ukat/L Standard Deviation 0.1267

PRIMARY outcome

Timeframe: From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Population: Full analysis set. For each lab test, number of patients is the number of patients with available change from baseline value.

Change from baseline in chemistry test Bilirubin.

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=172 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=175 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=347 Participants sum per row
Change From Baseline in Bilirubin, Full Analysis Set	-0.451 umol/L Standard Deviation 3.0980	-0.297 umol/L Standard Deviation 3.3972	-0.374 umol/L Standard Deviation 3.2486

SECONDARY outcome

Timeframe: From week 0 to week 184 in study treatment period and through the follow up period (12 weeks from day of last dose). Number and percentage of participants with asthma exacerbation during this period is presented.

Population: Full analysis set.

Asthma exacerbation is defined by a worsening of asthma requiring the use of systemic corticosteroids for at least 3 days, and/or an in patient hospitalization, and/or an emergency department or urgent care visit

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=220 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=226 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=446 Participants sum per row
Number of Participants With Asthma Exacerbations During Study Period	96 Participants	97 Participants	193 Participants

SECONDARY outcome

Timeframe: From week 0 to week 184 in study treatment period and through the follow up period (12 weeks from day of last dose). Number and percentage of participants with health care encounters during this period is presented.

Population: Full analysis set.

Hospitalizations, Emergency department (ED) visits, urgent care visits and all other outpatient visits due to asthma

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=220 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=226 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=446 Participants sum per row
Number of Participants Who Had Health Care Encounter (ie, Hospitalization, Emergency Department Visits, Urgent Care Visits, and All Other Outpatient Visits Due to Asthma) During Study Period	25 Participants	28 Participants	53 Participants

SECONDARY outcome

Timeframe: From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented.

Population: Full analysis set.

Change from Baseline to End of Treatment in blood eosinophils count.

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=173 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=178 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=351 Participants sum per row
Change of Blood Eosinophils Count	12.3 cell/uL Standard Deviation 50.24	-12.9 cell/uL Standard Deviation 212.51	-0.5 cell/uL Standard Deviation 155.68

SECONDARY outcome

Timeframe: From week 0 to week 184 in study treatment period and plus 12 weeks follow up period

Population: Full analysis set.

Assessments for the presence of ADA and neutralizing antibody (nAb) throughout study

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=220 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=226 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=446 Participants sum per row
Number of Participants With Anti-drug Antibodies (ADA) Responses During the Study Positive at any visit	19 Participants	28 Participants	47 Participants
Number of Participants With Anti-drug Antibodies (ADA) Responses During the Study Both baseline and post-baseline positive	11 Participants	17 Participants	28 Participants
Number of Participants With Anti-drug Antibodies (ADA) Responses During the Study Only post-baseline positive	7 Participants	10 Participants	17 Participants
Number of Participants With Anti-drug Antibodies (ADA) Responses During the Study ADA Persistently Positive	12 Participants	21 Participants	33 Participants
Number of Participants With Anti-drug Antibodies (ADA) Responses During the Study ADA Transiently Positive	6 Participants	6 Participants	12 Participants
Number of Participants With Anti-drug Antibodies (ADA) Responses During the Study Only baseline positive	1 Participants	1 Participants	2 Participants
Number of Participants With Anti-drug Antibodies (ADA) Responses During the Study nAb positive	13 Participants	24 Participants	37 Participants
Number of Participants With Anti-drug Antibodies (ADA) Responses During the Study nAb positive in ADA positive participants	13 Participants	24 Participants	37 Participants

SECONDARY outcome

Timeframe: From week 0 to week 184 in study treatment period

Population: Full analysis set.

Duration of exposure

Outcome measures

Outcome measures
Measure	Benra 30 mg q.4 Weeks n=220 Participants Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=226 Participants Benralizumab administered subcutaneously every 8 weeks	Total n=446 Participants sum per row
Duration of Exposure	26.35 months Standard Deviation 10.112	25.36 months Standard Deviation 9.939	25.85 months Standard Deviation 10.026

Adverse Events

Benra 30 mg q.4 Weeks

Serious events: 44 serious events

Other events: 169 other events

Deaths: 1 deaths

Benra 30 mg q.8 Weeks

Serious events: 47 serious events

Other events: 145 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

AstraZeneca Information Center

AstraZeneca

Phone: +1 8002369933

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee ≥ 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Benra 30 mg q.4 Weeks n=220 participants at risk Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=226 participants at risk Benralizumab administered subcutaneously every 8 weeks
Gastrointestinal disorders Diarrhoea	3.6% 8/220 • Number of events 12 • All participants completed treatment period up to Week 184.	2.7% 6/226 • Number of events 6 • All participants completed treatment period up to Week 184.
General disorders Influenza like illness	3.2% 7/220 • Number of events 9 • All participants completed treatment period up to Week 184.	3.5% 8/226 • Number of events 10 • All participants completed treatment period up to Week 184.
Infections and infestations Acute sinusitis	5.9% 13/220 • Number of events 20 • All participants completed treatment period up to Week 184.	3.5% 8/226 • Number of events 10 • All participants completed treatment period up to Week 184.
Infections and infestations Bronchitis	10.5% 23/220 • Number of events 33 • All participants completed treatment period up to Week 184.	9.7% 22/226 • Number of events 26 • All participants completed treatment period up to Week 184.
Infections and infestations Bronchitis bacterial	5.5% 12/220 • Number of events 17 • All participants completed treatment period up to Week 184.	4.0% 9/226 • Number of events 13 • All participants completed treatment period up to Week 184.
Infections and infestations Influenza	2.7% 6/220 • Number of events 6 • All participants completed treatment period up to Week 184.	4.4% 10/226 • Number of events 10 • All participants completed treatment period up to Week 184.
Infections and infestations Nasopharyngitis	30.5% 67/220 • Number of events 126 • All participants completed treatment period up to Week 184.	28.3% 64/226 • Number of events 112 • All participants completed treatment period up to Week 184.
Infections and infestations Pharyngitis	4.5% 10/220 • Number of events 19 • All participants completed treatment period up to Week 184.	1.3% 3/226 • Number of events 3 • All participants completed treatment period up to Week 184.
Infections and infestations Rhinitis	5.0% 11/220 • Number of events 18 • All participants completed treatment period up to Week 184.	1.3% 3/226 • Number of events 3 • All participants completed treatment period up to Week 184.
Infections and infestations Sinusitis	7.7% 17/220 • Number of events 26 • All participants completed treatment period up to Week 184.	4.4% 10/226 • Number of events 16 • All participants completed treatment period up to Week 184.
Infections and infestations Sinusitis bacterial	1.8% 4/220 • Number of events 6 • All participants completed treatment period up to Week 184.	3.1% 7/226 • Number of events 10 • All participants completed treatment period up to Week 184.
Infections and infestations Upper respiratory tract infection	6.4% 14/220 • Number of events 20 • All participants completed treatment period up to Week 184.	3.5% 8/226 • Number of events 12 • All participants completed treatment period up to Week 184.
Infections and infestations Upper respiratory tract infection bacterial	4.5% 10/220 • Number of events 19 • All participants completed treatment period up to Week 184.	3.5% 8/226 • Number of events 10 • All participants completed treatment period up to Week 184.
Infections and infestations Urinary tract infection	3.2% 7/220 • Number of events 9 • All participants completed treatment period up to Week 184.	3.1% 7/226 • Number of events 7 • All participants completed treatment period up to Week 184.
Infections and infestations Viral upper respiratory tract infection	13.2% 29/220 • Number of events 38 • All participants completed treatment period up to Week 184.	8.4% 19/226 • Number of events 21 • All participants completed treatment period up to Week 184.
Musculoskeletal and connective tissue disorders Arthralgia	3.2% 7/220 • Number of events 7 • All participants completed treatment period up to Week 184.	3.5% 8/226 • Number of events 9 • All participants completed treatment period up to Week 184.
Musculoskeletal and connective tissue disorders Back pain	5.0% 11/220 • Number of events 14 • All participants completed treatment period up to Week 184.	4.4% 10/226 • Number of events 10 • All participants completed treatment period up to Week 184.
Musculoskeletal and connective tissue disorders Osteoarthritis	4.5% 10/220 • Number of events 14 • All participants completed treatment period up to Week 184.	1.3% 3/226 • Number of events 3 • All participants completed treatment period up to Week 184.
Nervous system disorders Dizziness	3.2% 7/220 • Number of events 9 • All participants completed treatment period up to Week 184.	0.88% 2/226 • Number of events 2 • All participants completed treatment period up to Week 184.
Nervous system disorders Headache	14.5% 32/220 • Number of events 56 • All participants completed treatment period up to Week 184.	9.3% 21/226 • Number of events 41 • All participants completed treatment period up to Week 184.
Respiratory, thoracic and mediastinal disorders Asthma	7.3% 16/220 • Number of events 21 • All participants completed treatment period up to Week 184.	8.8% 20/226 • Number of events 40 • All participants completed treatment period up to Week 184.
Respiratory, thoracic and mediastinal disorders Nasal polyps	3.2% 7/220 • Number of events 10 • All participants completed treatment period up to Week 184.	1.8% 4/226 • Number of events 4 • All participants completed treatment period up to Week 184.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	1.8% 4/220 • Number of events 8 • All participants completed treatment period up to Week 184.	3.5% 8/226 • Number of events 12 • All participants completed treatment period up to Week 184.
Vascular disorders Hypertension	6.4% 14/220 • Number of events 23 • All participants completed treatment period up to Week 184.	10.6% 24/226 • Number of events 31 • All participants completed treatment period up to Week 184.