ALIZE: Study to Evaluate the Potential Effect of Benralizumab on the Humoral Immune Response to the Seasonal Influenza Vaccination in Adolescent and Young Adult Patients With Severe Asthma

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02814643
• Collaborator: (none)
• Enrollment: 103
• Locations: 24
• Arms: 2
• Actual Duration (Months): 6.8
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, parallel group, placebo-controlled study designed to investigate the potential effect of a fixed dose of benralizumab administered subcutaneously (SC) on antibody responses following seasonal influenza virus vaccination

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Benralizumab; Drug: Benralizumab Placebo; Drug: Seasonal influenza virus vaccine	Phase 3

Detailed Description

This study is designed to investigate the potential effect of benralizumab on the antibody response to the seasonal influenza virus vaccine in patients 12-21 years of age with asthma. Benralizumab will be given subcutaneously (SC) at Weeks 0, 4, and 8 weeks, at which time benralizumab levels will reach steady state. Patients will then receive 1 dose of intramuscular (IM) seasonal influenza virus vaccine at Week 8 and samples drawn at Week 8 and Week 12 to measure the antibody response to the influenza virus

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3b Study to Evaluate the Potential Effect of Benralizumab on the Humoral Immune Response to the Seasonal Influenza Vaccination in Adolescent and Young Adult Patients With Severe Asthma.
• Actual Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Jan 24, 2017
• Actual Study Completion Date: Jan 24, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Benralizumab 1 mL fill volume administered every 4 weeks for 3 doses (Weeks 0, 4, and 8). Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.	Drug: Benralizumab; Benralizumab SC administered every 4 weeks for 3 doses (Weeks 0, 4, and 8).; Drug: Seasonal influenza virus vaccine; Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.
Placebo Comparator: Placebo 1 mL fill volume administered every 4 weeks for 3 doses (Weeks 0, 4, and 8). Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.	Drug: Benralizumab Placebo; Placebo administered every 4 weeks for 3 doses (Weeks 0, 4, and 8).; Drug: Seasonal influenza virus vaccine; Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.

Outcome Measures

Primary Outcome Measures

1. Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 [4 weeks]

   To compare the geometric mean fold rises in influenza strain-specific hemagglutination-inhibition responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean [log(z) x]), where "x" is the postdose HAI antibody titer fold rise from Week 8 and "z" is the natural logarithm.

2. Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 [12 weeks]

   To compare the geometric mean titers of hemagglutination-inhibition antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.

3. Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 [4 weeks]

   To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in hemagglutination-inhibition antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.

4. Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 [12 weeks]

   To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥40-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.

Secondary Outcome Measures

1. Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 [12 weeks]

   To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥320-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.

2. Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 [4 weeks]

   To compare the geometric mean fold rises in influenza strain-specific microneutralization antibody responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean [log(z) x]), where "x" is the postdose microneutralization antibody titer fold rise from Week 8 and "z" is the natural logarithm.

3. Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 [12 weeks]

   To compare the geometric mean titers of microneutralization antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.

4. Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 [4 weeks]

   To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in microneutralization antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.

5. Change From Baseline in Mean Asthma Control Questionnaire 6 (ACQ-6) Score at Week 12 [12 weeks]

   To compare the change from baseline at Week 12 in mean ACQ-6 score between patients receiving benralizumab 30mg and patients receiving placebo. The ACQ-6 assesses asthma symptoms (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and short-acting β2 agonist use). Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses to each question. Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled asthma, and a score >1.5 indicates not well controlled asthma

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female and male patients aged 12 to 21 years, inclusive, at the time of Visit 1

• Weight of ≥40 kg

• Documented history of current treatment with Inhaled corticosteroids (ICS) and long-acting β2 agonists (LABA)

• Morning pre-bronchodilator forced expiratory volume in 1 second (FEV1) of >50% predicted at Visit 1 or Visit 2.

• Airway reversibility (FEV1 >12% and 200 ml) demonstrated at Visit 1 or Visit 2 using the Maximum Post-bronchodilator Procedure OR

• Airway reversibility documented in the previous 12 months prior to Visit 1

• An exacerbation, 1 or more, that required oral corticosteroids in the previous year OR

• Any condition assessed by patient recall over the previous 2-4 weeks

Exclusion Criteria:

• Clinically important pulmonary disease other than asthma

• Known history of allergy or reaction to the Investigational Product formulation or influenza vaccine

• Receipt of an influenza vaccine within 90 days prior to randomization

• Poorly controlled asthma during the screening period that requires treatment with oral corticosteroids or a hospitalization/emergency room visit for the treatment of asthma

• Acute illness or evidence of significant active infection or known influenza infection during the current flu season

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35209
2	Research Site	Mesa	Arizona	United States	85206
3	Research Site	Huntington Beach	California	United States	92647
4	Research Site	Newport Beach	California	United States	92663
5	Research Site	Aurora	Colorado	United States	80012-4016
6	Research Site	Colorado Springs	Colorado	United States	80907
7	Research Site	Denver	Colorado	United States	80230
8	Research Site	Aventura	Florida	United States	33180
9	Research Site	Miami	Florida	United States	33135
10	Research Site	Miami	Florida	United States	33173
11	Research Site	Minneapolis	Minnesota	United States	55402
12	Research Site	Bellevue	Nebraska	United States	68123
13	Research Site	Northfield	New Jersey	United States	08225
14	Research Site	Edmond	Oklahoma	United States	73034
15	Research Site	Oklahoma City	Oklahoma	United States	73103
16	Research Site	Medford	Oregon	United States	97504
17	Research Site	North Charleston	South Carolina	United States	29420
18	Research Site	Arlington	Texas	United States	76018
19	Research Site	El Paso	Texas	United States	79903
20	Research Site	New Braunfels	Texas	United States	78130
21	Research Site	San Antonio	Texas	United States	78221
22	Research Site	San Antonio	Texas	United States	78251
23	Research Site	Waco	Texas	United States	76712
24	Research Site	Clinton	Utah	United States	84015

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Pamela L Zeitlin, M.D. Ph.D., Johns Hopkins University

Study Documents (Full-Text)

• Study Protocol - Dec 14, 2015
• Statistical Analysis Plan - Mar 6, 2017

More Information

Additional Information:

• CSP redacted
• Statistical Analysis Plan (SAP)
• ALIZE_redacted_protocol.pdf

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02814643
• Other Study ID Numbers: D3250C00033
• First Posted: Jun 28, 2016
• Last Update Posted: Oct 24, 2018
• Last Verified: Oct 1, 2018

• Keywords provided by AstraZeneca: Male and female adolescent patients; severe asthma
• Additional relevant MeSH terms: Asthma; Benralizumab

Study Results

Participant Flow

Recruitment Details	This study was conducted at 30 study centers in the United States between 01 July 2016 and 24 January 2017
Pre-assignment Detail	The study duration was up to 23 weeks, consisting of an initial screening period lasting up to 3 weeks, a 12-week treatment period, and a follow-up visit 8 weeks after the last dose of study drug

Arm/Group Title	Benralizumab 30mg	Placebo
Arm/Group Description	Benralizumab 30mg/day subcutaneous	Placebo to benralizumab subcutaneous
Period Title: Overall Study
STARTED	51	52
COMPLETED	50	49
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Benralizumab 30mg	Placebo	Total
Arm/Group Description	Benralizumab 30mg/day subcutaneous	Placebo to benralizumab subcutaneous	Total of all reporting groups
Overall Participants	51	52	103
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	16.0 (2.65)	15.7 (2.99)	15.9 (2.82)
Age, Customized (Number) [Number]
≥12 to ≤17	36 70.6%	36 69.2%	72 69.9%
≥18 to ≤21	15 29.4%	16 30.8%	31 30.1%
Sex/Gender, Customized (Number) [Number]
Female	21 41.2%	21 40.4%	42 40.8%
Male	30 58.8%	31 59.6%	61 59.2%
Race/Ethnicity, Customized (Number) [Number]
American Indian Or Alaska Native	0 0%	1 1.9%	1 1%
Black Or African American	13 25.5%	13 25%	26 25.2%
Other	0 0%	2 3.8%	2 1.9%
White	38 74.5%	36 69.2%	74 71.8%

Outcome Measures

1. Primary Outcome

Title	Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12
Description	To compare the geometric mean fold rises in influenza strain-specific hemagglutination-inhibition responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean [log(z) x]), where "x" is the postdose HAI antibody titer fold rise from Week 8 and "z" is the natural logarithm.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

The vaccine immunogenicity analysis set included all randomized patients who received ≥1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or microneutralization antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

Arm/Group Title	Benralizumab 30mg	Placebo
Arm/Group Description	Benralizumab 30mg/day subcutaneous	Placebo to benralizumab subcutaneous
Measure Participants	50	49
Influenza A H1N1	3.60 (1.22)	3.13 (1.22)
Influenza A H3N2	3.25 (1.18)	3.85 (1.18)
Influenza B Yamagata lineage	3.42 (1.16)	3.17 (1.16)
Influenza B Victoria lineage	4.08 (1.19)	3.27 (1.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30mg, Placebo
	Comments	Influenza A H1N1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least-square mean ratio
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 90%; 0.56 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30mg, Placebo
	Comments	Influenza A H3N2
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least-square mean ratio
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 90%; 0.82 to 1.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30mg, Placebo
	Comments	Influenza B Yamagata lineage
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least-square mean ratio
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 90%; 0.67 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30mg, Placebo
	Comments	Influenza B Victoria lineage
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least-square mean ratio
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 90%; 0.54 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12
Description	To compare the geometric mean titers of hemagglutination-inhibition antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

Arm/Group Title	Benralizumab 30mg	Placebo
Arm/Group Description	Benralizumab 30mg/day subcutaneous	Placebo to benralizumab subcutaneous
Measure Participants	50	49
Influenza A H1N1	521.06 (1.13)	518.60 (1.13)
Influenza A H3N2	170.73 (1.15)	219.35 (1.15)
Influenza B Yamagata lineage	61.47 (1.13)	63.15 (1.13)
Influenza B Victoria lineage	53.10 (1.14)	66.85 (1.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30mg, Placebo
	Comments	Influenza A H1N1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least-square mean ratio
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 90%; 0.76 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30mg, Placebo
	Comments	Influenza A H3N2
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least-square mean ratio
	Estimated Value	1.28
	Confidence Interval	(2-Sided) 90%; 0.93 to 1.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30mg, Placebo
	Comments	Influenza B Yamagata lineage
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least-square mean ratio
	Estimated Value	1.03
	Confidence Interval	() 90%; 0.79 to 1.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Benralizumab 30mg, Placebo
	Comments	Influenza B Victoria lineage
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric least-square mean ratio
	Estimated Value	1.26
	Confidence Interval	() 90%; 0.93 to 1.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12
Description	To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in hemagglutination-inhibition antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

Arm/Group Title	Benralizumab 30mg	Placebo
Arm/Group Description	Benralizumab 30mg/day subcutaneous	Placebo to benralizumab subcutaneous
Measure Participants	50	49
Influenza A H1N1	0.440 0.9%	0.306 0.6%
Influenza A H3N2	0.500 1%	0.490 0.9%
Influenza B Yamagata lineage	0.480 0.9%	0.490 0.9%
Influenza B Victoria lineage	0.560 1.1%	0.408 0.8%

4. Primary Outcome

Title	Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12
Description	To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥40-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

Arm/Group Title	Benralizumab 30mg	Placebo
Arm/Group Description	Benralizumab 30mg/day subcutaneous	Placebo to benralizumab subcutaneous
Measure Participants	50	49
Influenza A H1N1	1.00 (251.9) 2%	1.00 (191.3) 1.9%
Influenza A H3N2	0.980 (136.2) 1.9%	0.980 (168.6) 1.9%
Influenza B Yamagata lineage	0.860 (144.9) 1.7%	0.796 (115.0) 1.5%
Influenza B Victoria lineage	0.780 (178.7) 1.5%	0.878 (162.2) 1.7%

5. Secondary Outcome

Title	Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12
Description	To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥320-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

Arm/Group Title	Benralizumab 30mg	Placebo
Arm/Group Description	Benralizumab 30mg/day subcutaneous	Placebo to benralizumab subcutaneous
Measure Participants	50	49
Influenza A H1N1	0.840 1.6%	0.857 1.6%
Influenza A H3N2	0.500 1%	0.612 1.2%
Influenza B Yamagata lineage	0.020 0%	0.020 0%
Influenza B Victoria lineage	0.080 0.2%	0.041 0.1%

6. Secondary Outcome

Title	Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12
Description	To compare the geometric mean fold rises in influenza strain-specific microneutralization antibody responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean [log(z) x]), where "x" is the postdose microneutralization antibody titer fold rise from Week 8 and "z" is the natural logarithm.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

Arm/Group Title	Benralizumab 30mg	Placebo
Arm/Group Description	Benralizumab 30mg/day subcutaneous	Placebo to benralizumab subcutaneous
Measure Participants	50	49
Influenza A H1N1	5.1 (521.4)	4.4 (329.4)
Influenza A H3N2	3.2 (149.8)	3.6 (210.0)
Influenza B Yamagata lineage	2.8 (148.9)	3.2 (141.3)
Influenza B Victoria lineage	3.8 (224.1)	3.5 (195.3)

7. Secondary Outcome

Title	Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12
Description	To compare the geometric mean titers of microneutralization antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

Arm/Group Title	Benralizumab 30mg	Placebo
Arm/Group Description	Benralizumab 30mg/day subcutaneous	Placebo to benralizumab subcutaneous
Measure Participants	50	49
Influenza A H1N1	3774.1 (181.7)	3969.1 (154.0)
Influenza A H3N2	4307.5 (169.0)	4351.3 (171.0)
Influenza B Yamagata lineage	350.2 (103.6)	336.2 (114.3)
Influenza B Victoria lineage	164.5 (178.5)	234.4 (135.0)

8. Secondary Outcome

Title	Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12
Description	To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in microneutralization antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

Arm/Group Title	Benralizumab 30mg	Placebo
Arm/Group Description	Benralizumab 30mg/day subcutaneous	Placebo to benralizumab subcutaneous
Measure Participants	50	49
Influenza A H1N1	0.420 (251.9) 0.8%	0.408 (191.3) 0.8%
Influenza A H3N2	0.440 (136.2) 0.9%	0.429 (168.6) 0.8%
Influenza B Yamagata lineage	0.280 (144.9) 0.5%	0.388 (115.0) 0.7%
Influenza B Victoria lineage	0.400 (178.7) 0.8%	0.388 (162.2) 0.7%

9. Secondary Outcome

Title	Change From Baseline in Mean Asthma Control Questionnaire 6 (ACQ-6) Score at Week 12
Description	To compare the change from baseline at Week 12 in mean ACQ-6 score between patients receiving benralizumab 30mg and patients receiving placebo. The ACQ-6 assesses asthma symptoms (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and short-acting β2 agonist use). Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses to each question. Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled asthma, and a score >1.5 indicates not well controlled asthma
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set included all patients who were randomized and received any investigational product.

Arm/Group Title	Benralizumab 30mg	Placebo
Arm/Group Description	Benralizumab 30mg/day subcutaneous	Placebo to benralizumab subcutaneous
Measure Participants	50	49
Mean (Full Range) [Score on a scale]	-0.50	-0.42

Adverse Events

Time Frame	All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Arm/Group Title	Benralizumab 30mg		Placebo
Arm/Group Description	Benralizumab 30mg/day subcutaneous		Placebo to benralizumab subcutaneous
All Cause Mortality
	Benralizumab 30mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/52 (0%)
Serious Adverse Events
	Benralizumab 30mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		2/52 (3.8%)
Psychiatric disorders
Suicidal ideation	0/51 (0%)	0	1/52 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	0/51 (0%)	0	1/52 (1.9%)	1
Other (Not Including Serious) Adverse Events
	Benralizumab 30mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/51 (54.9%)		23/52 (44.2%)
Gastrointestinal disorders
Abdominal discomfort	2/51 (3.9%)	2	0/52 (0%)	0
Nausea	1/51 (2%)	1	2/52 (3.8%)	2
Infections and infestations
Gastroenteritis viral	3/51 (5.9%)	3	1/52 (1.9%)	1
Nasopharyngitis	2/51 (3.9%)	2	4/52 (7.7%)	5
Sinusitis	2/51 (3.9%)	2	1/52 (1.9%)	1
Upper respiratory tract infection	3/51 (5.9%)	4	1/52 (1.9%)	1
Viral upper respiratory tract infection	2/51 (3.9%)	2	0/52 (0%)	0
Injury, poisoning and procedural complications
Ligament sprain	2/51 (3.9%)	2	0/52 (0%)	0
Musculoskeletal and connective tissue disorders
Costochondritis	2/51 (3.9%)	3	0/52 (0%)	0
Nervous system disorders
Headache	2/51 (3.9%)	3	4/52 (7.7%)	4
Respiratory, thoracic and mediastinal disorders
Asthma	3/51 (5.9%)	5	3/52 (5.8%)	3
Cough	0/51 (0%)	0	3/52 (5.8%)	3
Oropharyngeal pain	3/51 (5.9%)	4	2/52 (3.8%)	2
Skin and subcutaneous tissue disorders
Acne	1/51 (2%)	1	2/52 (3.8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

At least 30 days prior to submission 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 Institution 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/presentation.