Benralizumab does not impair antibody response to seasonal influenza vaccination in adolescent and young adult patients with moderate to severe asthma: results from the Phase IIIb ALIZE trial

Figures & data

Figure 1 Study design.

Abbreviations: ARE, antibody response evaluation; EOT, end of treatment; FU, follow-up; SC, subcutaneous.

Figure 2 Consolidated standards of reporting (CONSORT) flow diagram.

Table 1 Patient demographics and baseline clinical characteristics (full analysis set)

	Benralizumab 30 mg Q4W (N=51)	Placebo (N=52)	Total (N=103)
Age [years], median (range)	16 (12–21)	16 (12–21)	16 (12–21)
Female, n (%)	21 (41.2)	21 (40.4)	42 (40.8)
Race, n (%)
White	38 (74.5)	36 (69.2)	74 (71.8)
American Indian or Alaska Native	0 (0)	1 (1.9)	1 (1.0)
Black or African-American	13 (25.5)	13 (25.0)	26 (25.2)
Other	0 (0)	2 (3.8)	2 (1.9)
BMI [kg/m^2], mean (SD)	25.4 (7.0)	23.9 (5.1)	24.6 (6.1)
Asthma triggers, n (%)
Allergens	42 (82.4)	44 (84.6)	86 (83.5)
Aspirin	0 (0)	0 (0)	0 (0)
Exercise	34 (66.7)	39 (75.0)	73 (70.9)
Other	16 (31.4)	24 (46.2)	40 (38.8)
Exacerbations during the previous
12 months, n (%)
0	32 (62.7)	33 (63.5)	65 (63.1)
1	11 (21.6)	12 (23.1)	23 (22.3)
≥2	8 (15.7)	7 (13.4)	15 (14.6)
FEV1 prebronchodilator [L], mean (SD)	2.854 (0.675)	2.622 (0.665)	2.737 (0.677)
FEV1 prebronchodilator [% predicted normal], mean (SD)	79.91 (14.15)	76.79 (14.45)	78.34 (14.32)
FEV1/FVC prebronchodilator [%], mean (SD)	75.31 (8.87)	75.55 (10.37)	75.43 (9.61)
FEV1 reversibility [%], median (range)	14.98 (−9.25–44.00)	18.00 (−2.24–48.51)	16.06 (−9.25–48.51)

Abbreviations: BMI, body mass index; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; N, number of patients within each treatment group; n, number of patients in specified subgroup; Q4W, every 4 weeks; SD, standard deviation.

Figure 3 Influenza strain antibody geometric mean fold rise from Week 8 to Week 12 for (A) hemagglutination inhibition and (B) microneutralization (vaccine immunogenicity analysis set).

Note: Error bars represent geometric SD.
Abbreviation: Q4W, every 4 weeks.

Table 2 Influenza strain antibody response for hemagglutination inhibition (vaccine immunogenicity analysis set)

Antibody response measure	Benralizumab 30 mg Q4W (N=50)	Placebo (N=49)
GMT Week 8, GM (GSD; CV%)
Influenza A, H1N1	145.9 (3.6; 205.1)	166.9 (2.8; 136.6)
Influenza A, H3N2	62.3 (3.7; 209.6)	67.2 (3.4; 185.3)
Influenza B, Yamagata lineage	16.6 (2.6; 122.6)	18.5 (2.6; 123.5)
Influenza B, Victoria lineage	13.6 (2.5; 111.2)	21.4 (3.2; 167.1)
GMT Week 12, GM (GSD; CV%)
Influenza A, H1N1	570.2 (2.4; 107.9)	566.1 (2.2; 93.2)
Influenza A, H3N2	206.3 (2.9; 146.6)	263.7 (2.7; 126.7)
Influenza B, Yamagata lineage	60.3 (2.2; 93.1)	62.0 (2.2; 93.2)
Influenza B, Victoria lineage	57.9 (2.7; 126.2)	72.8 (2.3; 99.4)
GMFR Week 8 to Week 12, GM (GSD; CV%)
Influenza A, H1N1	3.9 (4.1; 251.9)	3.4 (3.5; 191.3)
Influenza A, H3N2	3.3 (2.8; 136.2)	3.9 (3.2; 168.6)
Influenza B, Yamagata lineage	3.6 (2.9; 144.9)	3.4 (2.5; 115.0)
Influenza B, Victoria lineage	4.2 (3.3; 178.7)	3.4 (3.1; 162.2)
GMT Week 12 geometric LS mean estimate (LS mean ratio; 90% CIa)
Influenza A, H1N1	521.1 (1.00; 0.76–1.31)	518.6
Influenza A, H3N2	170.7 (1.28; 0.93–1.77)	219.4
Influenza B, Yamagata lineage	61.5 (1.03; 0.79–1.34)	63.2
Influenza B, Victoria lineage	53.1 (1.26; 0.93–1.70)	66.8
GMFR Week 12 geometric LS mean estimate (LS mean ratio; 90% CIa)
Influenza A, H1N1	3.6 (0.87; 0.56–1.35)	3.1
Influenza A, H3N2	3.3 (1.19; 0.82–1.71)	3.9
Influenza B, Yamagata lineage	3.4 (0.93; 0.67–1.29)	3.2
Influenza B, Victoria lineage	4.1 (0.8; 0.54–1.19)	3.3
Antibody titer ≥4-fold rise from Week 8 to Week 12, n (90% CIb) [%]
Influenza A, H1N1	22 (0.32–0.57) [44.0]	15 (0.20–0.43) [30.6]
Influenza A, H3N2	25 (0.38–0.62) [50.0]	24 (0.37–0.62) [49.0]
Influenza B, Yamagata lineage	24 (0.36–0.60) [48.0]	24 (0.37–0.62) [49.0]
Influenza B, Victoria lineage	28 (0.43–0.68) [56.0]	20 (0.29–0.54) [40.8]
Antibody titer ≥40 at Week 12, n (90% CIb) [%]
Influenza A, H1N1	50 (0.94–1.00) [100.0]	49 (0.94–1.00) [100.0]
Influenza A, H3N2	49 (0.91–1.00) [98.0]	48 (0.91–1.00) [98.0]
Influenza B, Yamagata lineage	43 (0.75–0.93) [86.0]	39 (0.68–0.88) [79.6]
Influenza B, Victoria lineage	39 (0.66–0.87) [78.0]	43 (0.77–0.95) [87.8]
Antibody titer ≥320 at Week 12, n (90% CIb) [%]
Influenza A, H1N1	42 (0.73–0.92) [84.0]	42 (0.75–0.93) [85.7]
Influenza A, H3N2	25 (0.38–0.62) [50.0]	30 (0.48–0.73) [61.2]
Influenza B, Yamagata lineage	1 (0.00–0.09) [2.0]	1 (0.00–0.09) [2.0]
Influenza B, Victoria lineage	4 (0.03–0.17) [8.0]	2 (0.01–0.12) [4.1]

Notes:

a 90% CIs are for treatment comparison between benralizumab and placebo.

b Results using the Clopper–Pearson method.

Abbreviations: CV%, geometric coefficient of variation; GM, geometric mean; GMFR, geometric mean fold rise; GMT, geometric mean titer; GSD, geometric standard deviation; LS, least squares; N, number of patients within each treatment group; n, number of patients in analysis; Q4W, every 4 weeks.

Table 3 Influenza strain antibody response for microneutralization (vaccine immunogenicity analysis set)

Antibody response measure	Benralizumab 30 mg Q4W (N=50)	Placebo (N=49)
GMT Week 8, GM (GSD; CV%)
Influenza A, H1N1	735.2 (4.2; 263.0)	898.7 (3.4; 188.9)
Influenza A, H3N2	1,353.0 (2.5; 114.7)	1,218.2 (2.7; 132.2)
Influenza B, Yamagata lineage	123.0 (2.7; 129.8)	106.2 (2.7; 129.4)
Influenza B, Victoria lineage	43.7 (2.8; 138.4)	67.0 (3.5; 196.8)
GMT Week 12, GM (GSD; CV%)
Influenza A, H1N1	3,774.1 (3.4; 181.7)	3,969.1 (3.0; 154.0)
Influenza A, H3N2	4,307.5 (3.2; 169.0)	4,351.3 (3.2; 171.0)
Influenza B, Yamagata lineage	350.2 (2.4; 103.6)	336.2 (2.5; 114.3)
Influenza B, Victoria lineage	164.5 (3.3; 178.5)	234.4 (2.8; 135.0)
GMFR Week 8 to Week 12, GM (GSD; CV%)
Influenza A, H1N1	5.1 (6.2; 521.4)	4.4 (4.8; 329.4)
Influenza A, H3N2	3.2 (3.0; 149.8)	3.6 (3.7; 210.0)
Influenza B, Yamagata lineage	2.8 (3.0; 148.9)	3.2 (2.9; 141.3)
Influenza B, Victoria lineage	3.8 (3.8; 224.1)	3.5 (3.5; 195.3)
Antibody titer ≥4-fold rise from Week 8 to Week 12, n (90% CIa) [%]
Influenza A, H1N1	21 (0.30–0.55) [42.0]	20 (0.29–0.54) [40.8]
Influenza A, H3N2	22 (0.32–0.57) [44.0]	21 (0.31–0.56) [42.9]
Influenza B, Yamagata lineage	14 (0.18–0.40) [28.0]	19 (0.27–0.52) [38.8]
Influenza B, Victoria lineage	20 (0.28–0.53) [40.0]	19 (0.27–0.52) [38.8]

Note:

a Results using the Clopper–Pearson method.

Abbreviations: CV%, geometric coefficient of variation; GM, geometric mean; GMFR, geometric mean fold rise; GMT, geometric mean titer; GSD, geometric standard deviation; N, number of patients within each treatment group; n, number of patients in analysis; Q4W, every 4 weeks.

Table 4 ACQ-6 scores by time point (full analysis set)

Time point	Benralizumab 30 mg Q4W (N=51)			Placebo (N=52)
	n	Score	Change from baseline	n	Score	Change from baseline
Baseline, mean (SD)	51	1.95 (0.88)		52	1.76 (0.95)
Week 4, mean (SD)	51	1.47 (0.98)	−0.48 (0.98)	50	1.44 (0.88)	−0.30 (0.74)
Week 8, mean (SD)	50	1.47 (0.94)	−0.47 (0.89)	50	1.34 (0.78)	−0.39 (0.87)
Week 12, mean (SD)	50	1.44 (1.06)	−0.50 (1.11)	49	1.29 (0.83)	−0.42 (0.93)

Abbreviations: ACQ-6, Asthma Control Questionnaire 6; N, number of patients within each treatment group; n, number of patients in analysis; Q4W, every 4 weeks; SD, standard deviation.

Figure 4 Arithmetic mean (± SD) serum trough concentrations of benralizumab (PK analysis set).

Abbreviations: PK, pharmacokinetics; SD, standard deviation.

Table 5 Adverse events (safety analysis set)

AE category, n (%)	Benralizumab 30 mg Q4W (N=51)	Placebo (N=52)
Any AE	22 (43.1)	23 (44.2)
Any SAE (including events with outcome	0 (0)	2 (3.8)
of death)
Any AE of maximum intensity
Mild	10 (19.6)	12 (23.1)
Moderate	9 (17.6)	10 (19.2)
Severe	3 (5.9)	1 (1.9)
Any causally related AE	1 (2.0)	2 (3.8)
Asthma	3 (5.9)	4 (7.7)
Headache	2 (3.9)	4 (7.7)
Nasopharyngitis	2 (3.9)	4 (7.7)
Oropharyngeal pain	3 (5.9)	2 (3.8)
Viral gastroenteritis	3 (5.9)	1 (1.9)
Upper respiratory tract infection	3 (5.9)	1 (1.9)

Notes: Patients with several events in the same category are counted only once in that category. Patients with events in more than one category are counted once in each of those categories.

Abbreviations: AE, adverse event; N, number of patients within each treatment group; n, number of patients in subgroup; Q4W, every 4 weeks; SAE, serious AE.