Immunogenicity and safety of an egg-based inactivated quadrivalent influenza vaccine (GC3110A) versus two inactivated trivalent influenza vaccines with alternate B strains: A phase Ⅲ randomized clinical trial in adults

Figures & data

Table 1. Demographic characteristics of the study subjects.

	GC3110A (N = 647)	Control 1, TIV-Yamagata (N = 325)	Control 2, TIV-Victoria (N = 326)	p-value
Sex (male), no. (%)	244 (37.7)	124 (38.2)	130 (40.0)	0.803
Age (years), mean ± SD	40.6 ± 14.1	40.0 ± 14.8	41.0 ± 14.8	0.684
Age group, no. (%)				0.919
19– 64 years	583 (90.1)	292 (89.8)	291 (89.3)
≥ 65 years	64 (9.9)	33 (10.2)	35 (10.7)
Height, mean ± SD (cm)	164.6 ± 8.6	164.1 ± 8.6	164.6 ± 9.0	0.716
Body weight, mean ± SD (kg)	63.6 ± 12.1	63.0 ± 11.5	64.0 ± 12.9	0.597

SD, standard deviation

Figure 1. Flowchart of the subjects throughout the study.

Table 2. Post-vaccination non-inferiority analysis, as measured using a hemagglutination-inhibition (HI) assay (per-protocol population): trivalent influenza vaccines (controls) versus quadrivalent influenza vaccine (GC3110A).

Strains	Parameters	No	GMT or GMT ratio (95% CI)
Strain H1N1	GMT (GC3110A)	639	170.7 (156.1– 186.6)
	GMT (Control 1 + Control 2)^a	643	174.7 (159.8– 191.0)
	GMT ratio ([Control 1 + Control 2])/GC3110A)		1.0 (0.9– 1.2)
Strain H3N2	GMT (GC3110A)	639	124.8 (116.7– 133.4)
	GMT (Control 1 + Control 2)	643	120.2 (112.5– 128.5)
	GMT ratio ([Control 1 + Control 2])/GC3110A)		1.0 (0.9 −1.1)
Strain B Yamagata	GMT (GC3110A)	639	106.6 (100.3– 113.3)
	GMT (Control 1)	320	85.5 (78.5– 93.2)
	GMT ratio (Control 1/GC3110A)		0.8 (0.7– 0.9)
Strain B Victoria	GMT (GC3110A)	639	46.5 (43.4– 49.9)
	GMT (Control 2)	323	44.0 (39.9– 48.6)
	GMT ratio (Control 2/GC3110A)		1.0 (0.8– 1.1)
Strain	Parameters	No.	SCR or SCR difference (95% CI)
Strain H1N1	SCR (GC3110A)	639	56.2 % (52.2 to 60.1)
	SCR (Control 1 + Control 2)	643	59.6 % (55.7 to 63.4)
	SCR difference ([Control 1 + Control 2]) – GC3110A)		3.4 % (−2.0 to 8.8)
Strain H3N2	SCR (GC3110A)	639	59.3 % (55.4 to 63.2)
	SCR (Control 1 + Control 2)	643	55.8 % (51.9 to 59.7)
	SCR difference ([Control 1 + Control 2]) – GC3110A)		−3.5 % (−8.9 to 1.9)
Strain B Yamagata	SCR (GC3110A)	639	53.1 % (49.1 to 57.0)
	SCR (Control 1)	320	36.9 % (31.6 to 42.4)
	SCR difference (Control 1 – GC3110A)		−16.2 % (−22.8 to −9.5)
Strain B Victoria	SCR (GC3110A)	639	51.2 % (47.2 to 55.1)
	SCR (Control 2)	323	51.7 % (46.1 to 57.3)
	SCR difference (Control 2 – GC3110A)		0.5 % (−6.2 to 7.2)

GMT, geometric mean titer; SCR, seroconversion rate

^a Control 1, trivalent influenza vaccine containing Yamagata lineage B strain (TIV-Yamagata); Control 2, trivalent influenza vaccine containing Victoria lineage B strain (TIV-Victoria)

Table 3. Post-vaccination immune responses, as measured using a hemagglutination-inhibition (HI) assay (per-protocol population): quadrivalent influenza vaccine (GC3110A) and trivalent influenza vaccines (controls).

Strain	Age group	Parameters	GC3110A (No. = 575/64)^c	Control 1, TIV-Yamagata (No. = 288/32)^c	Control 2, TIV-Victoria (No. = 288/35)^c
H1N1	19–64 years	Seroprotection rate^a	96.9 (95.1 to 98.1)	96.2 (93.3 to 98.1)	96.5 (93.7 to 98.3)
		Seroconversion rate^b	57.7 (53.6 to 61.8)	56.9 (51.0 to 62.7)	65.3 (59.5 to 70.8)
	≥ 65 years	Seroprotection rate^a	79.7 (67.8 to 88.7)	68.8 (50.0 to 83.9)	82.9 (66.4 to 93.4)
		Seroconversion rate^b	42.2 (29.9 to 55.2)	37.5 (21.1 to 56.3)	54.3 (36.7 to 71.2)
H3N2	19–64 years	Seroprotection rate^a	94.1 (91.8 to 95.9)	96.9 (94.2 to 98.6)	93.4 (89.9 to 95.9)
		Seroconversion rate^b	60.4 (56.2 to 64.4)	54.2 (48.2 to 60.0)	60.8 (54.9 to 66.4)
	≥ 65 years	Seroprotection rate^a	92.2 (82.7 to 97.4)	87.5 (71.0 to 96.5)	97.1 (85.1 to 99.9)
		Seroconversion rate^b	50.0 (37.2 to 62.8)	28.1 (13.8 to 46.8)	54.3 (36.7 to 71.2)
B/Yamagata	19–64 years	Seroprotection rate^a	92.7 (90.3 to 94.7)	91.7 (87.9 to 94.6)	81.6 (76.6 to 85.9)
		Seroconversion rate^b	53.7 (50.0 to 57.9)	37.5 (31.9 to 43.4)	31.9 (26.6 to 37.7)
	≥ 65 years	Seroprotection rate^a	81.3 (69.5 to 89.9)	68.8 (50.0 to 83.9)	54.3 (36.7 to 71.2)
		Seroconversion rate^b	46.9 (34.3 to 59.8)	31.3 (16.1 to 50.0)	8.6 (1.8 to 23.1)
B/Victoria	19–64 years	Seroprotection rate^a	75.5 (68.7 to 76.1)	45.8 (40.0 to 51.8)	76.0 (70.7 to 80.9)
		Seroconversion rate^b	52.9 (48.7 to 57.0)	13.5 (9.8 to 18.0)	53.8 (47.9 to 59.7)
	≥ 65 years	Seroprotection rate^a	40.6 (28.5 to 53.6)	9.4 (2.0 to 25.0)	34.3 (19.1 to 52.2)
		Seroconversion rate^b	35.9 (24.3 to 48.9)	3.1 (0.1 to 16.2)	34.3 (19.1 to 52.2)

QIV, quadrivalent influenza vaccine; TIV-Yamagata, trivalent influenza vaccine containing Yamagata lineage B strain; TIV-Victoria, trivalent influenza vaccine containing Victoria lineage B strain

^a Seroprotection is defined as an HI titer ≥ 40; values are the percent of subjects in each group (with 95% CI in brackets).

^b Seroconversion is defined as follows: a pre-vaccination (day 0) HI titer < 1:10 and post-vaccination (day 21) HI titer ≥ 1:40; or a pre-vaccination (day 0) HI titer ≥ 1:10 and post-vaccination (day 21) HI titer with more than fourfold increase. Values are the percent of subjects in each group (with 95% CI in brackets).

^c Subject number is expressed as no. of subjects aged 19–64 years/no. of subjects aged ≥ 65 years.

Table 4. Solicited local and systemic adverse events within 21 days after vaccination: quadrivalent influenza vaccine (GC3110A) and trivalent influenza vaccines (controls).

Adverse event, No. (%)	GC3110A, QIV (N = 647)	Control 1, TIV-Yamagata (N = 325)	Control 2, TIV-Victoria (N = 326)	p-value^a
Solicited local event Grade 1 Grade 2 Grade 3 Grade 4	383 (59.2) 369 (57.0) 104 (16.1) 6 (0.9) 0 (0)	169 (52.0) 165 (50.8) 39 (12.0) 5 (1.5) 0 (0)	160 (49.1) 157 (48.2) 39 (12.0) 1 (0.3) 0 (0)	< 0.05
Pain	294 (45.4)	127 (39.1)	113 (34.7)	< 0.05
Tenderness	343 (53.0)	151 (46.5)	137 (42.0)	< 0.05
Redness/erythema	52 (8.0)	20 (6.2)	19 (5.8)	0.15
Induration/swelling	36 (5.6)	19 (5.9)	15 (4.6)	0.79
Solicited systemic event Grade 1 Grade 2 Grade 3 Grade 4	239 (36.9) 228 (35.2) 53 (8.2) 11 (1.7) 0 (0)	131 (40.3) 124 (38.2) 36 (11.1) 6 (1.9) 0 (0)	103 (31.6) 100 (30.7) 26 (8.0) 3 (0.9) 0 (0)	0.71
Fever	7 (1.1)	9 (2.8)	7 (2.2)	0.06
Headache	91 (14.1)	46 (14.2)	40 (12.3)	0.65
Fatigue	158 (24.4)	92 (28.3)	68 (20.9)	0.95
Malaise	50 (7.7)	27 (8.3)	21 (6.4)	0.81
Myalgia	163 (25.2)	82 (25.2)	71 (21.8)	0.48
Arthralgia	39 (6.0)	21 (6.5)	12 (3.7)	0.45
Nausea/vomiting	15 (2.3)	11 (3.4)	2 (0.6)	0.69
Diarrhea	15 (2.3)	7 (2.2)	8 (2.5)	0.99

QIV, quadrivalent influenza vaccine; TIV-Yamagata, trivalent influenza vaccine containing Yamagata lineage B strain; TIV-Victoria, trivalent influenza vaccine containing Victoria lineage B strain

^a GC3110A versus Controls (Control 1 + Control 2), chi-square test