Influvac Tetra: clinical experience on safety, efficacy, and immunogenicity

Figures & data

Table 1. List of studies conducted with Influvac Tetra.

Study	Target population	Country/Region	Type of study	Study period	Comparator	Number of vaccinated subjects	Efficacy endpoints
Esposito et al (INFQ3003)	Children aged 6–35 months	Europe and Asia	Phase III, randomized, double-blind, vaccine efficacy study	September 2017-January 2020	non-influenza vaccine	Total n = 2000 (QIV n = 1005 children; Control n = 995)	VE HI titers: pre/post vaccination GMT, GMFI, SCR, SPR VN titers: pre/post vaccination GMT, GMFI, SCR NI titers: pre/post vaccination GMT, GMFI, SCR
Kalappanavar et al (INFQ3004)	Children aged 6–35 months or 3–17 years, unprimed or primed	India	Phase III, open-label, baseline-controlled	August 2018-January 2019	-	Total n = 336 (118 children enrolled in each age group)	HI titer: pre/post vaccination GMT, GMFI, SCR, SPR
Vesikari et al (INFQ3002)	Children and adolescents 317 years of age.	Europe	Phase III, randomized, double-blind	September 2016-April 2017.	TIV	Total n = 1200 (QIV n = 402; TIV n = 404 with the B-strain of the Victoria lineage; TIV n = 394 with the B-strain of the Yamagata lineage)	HI titers: pre/post vaccination GMT, GMFI, SCR VN titers: pre/post vaccination GMT, GMFI, SCR NI titers: pre/post vaccination GMT, GMFI, SCR
van de Witte S et al (INFQ3001)	Adults and elderly	Europe	Phase III, randomized, double-blind, non-inferiority, immunogenicity study	May 2015-January 2016	TIV	Total n = 1980 (QIV n = 1538; TIV n = 221 with B-strain of the Victoria lineage; TIV n = 221 with B-strain of the Yamagata lineage)	HI titers: pre/post vaccination GMT, GMFI, SCR, SPR VN titers: pre/post vaccination GMT, GMFI, SCR
Basu et al (INFQ3005)	Adults and elderly	India	Phase III, randomized, observer-blind, immunogenicity study	March 2018-April 2018	VaxiFlu-4	Total n = 720 (QIV n = 480; VaxiFlu-4, n = 240	HI titers: pre/post vaccination GMT, GMFI, SCR, SPR

VE, Absolute vaccine efficacy of the QIV in the prevention of symptomatic influenza infection due to any circulating influenza strain/due to antigenically matching influenza strains; GMFI, geometric mean fold increase; GMT, geometric mean titer; GSD, geometric standard deviation; HI, hemagglutinin inhibition; NI, neuraminidase inhibition; VN, virus neutralization; TIV, trivalent influenza vaccine; QIV, Quadrivalent influenza vaccine.

Figure 1. Kaplan-Meier plot of time since 28 days post-second vaccination to RTPCR confirmed influenza A and/or B infection.

Figure 2. Influenza vaccine efficacy estimates due to antigenically matching influenza strains by age group.

Table 2. Comparison of post-vaccination seroconversion rates (%) across all the studies.

		A-H3N2		A-H1N1		B-strain Victoria lineage			B-strain Yamagata lineage
Study	Age group	QIV	TIV	QIV	TIV	QIV	TIVvic	TIVyam	QIV	TIVvic	TIVyam
3001	Adults	51.3	58.6	59.4	65.1	70.2	66.4	51.4	59.2	40.9	58.7
	Elderly	39.3	44.0	50.3	57.4	53.6	55.6	25.0	49.9	30.0	46.2
3002	3–8 years UNP	93.2	94.0	77.3	83.2	85.6	84.1	37.3	90.9	14.4	95.8
	3–8 years PRI	81.8	77.5	43.9	40.8	75.8	60.5	39.1	80.3	41.9	63.8
	9–17 years	67.4	74.0	59.1	58.7	68.2	73.2	42.0	66.7	28.3	62.6
		QIV		QIV		QIV			QIV
3003	6–35 months	92.5		74.4		26.5			35.5
3004	6–35 months	87.7		66.7		41.2			64.9
	3–17 years	89.0		78.8		69.5			75.4
		QIV	V-F 4	QIV	V-F 4	QIV	V-F 4		QIV	V-F 4
	Adults	75.4	74.4	83.9	75.2	48.3	54.5		48.3	46.3
3005	Elderly	66.9	75.9	73.7	79.3	42.4	47.4		40.7	36.2

UNP: unprimed; PRI: primed; vic, Victoria lineage; yam, Yamagata lineage; QIV, quadrivalent; TIV, Trivalent.

Table 3. Comparison of reactogenicity data (%) across all the studies.

		Incidence of local reactions (%)		Incidence of systemic reactions (%)
Study	Age group	QIV	Comparator	QIV	Comparator
INFQ3003	6–35 months	30.4	38.1	51.4	52.5
INFQ3004	6–35 months	13.6	-	16.9	-
	3–17 years	16.9	-	7.6	-
INFQ3002	3–17 years	62.7	57.9	38.1	38.1
INFQ3001	Adults	24.8	21.7	28.1	31.2
	Elderly	9.1	6.4	21.6	18.2
INFQ3005	Adults	5.0	6.6	5.8	4.1
	Elderly	0.8	1.7	3.4	2.5

QIV, Quadrivalent influenza vaccine.

Note: INFQ3003 study compared QIV with non-influenza control vaccine (NIV); INFQ3005 study compared QIV with VaxiFlu-4 vaccine; INFQ 3001, 3002 studies compared QIV with TIV.

Table 4. Non-inferiority of QIV versus TIV against shared strains based on post-vaccination geometric mean HI titers – per-protocol sample – study INFQ3002.

	QIV		TIV^a		TIV^a/QIV
Strain	N	GMT	N	GMT	Adjusted GMR (95% CI)
A(H1N1)	388	548.9	774	622.2	1.1 (0.98, 1.30)
A(H3N2)	388	1150	774	1194	1.0 (0.90, 1.19)
		QIV		TIV(Vic)	TIV(Vic)/QIV
B-Victoria	388	302.6	393	364.0	1.2 (0.98, 1.46)
		QIV		TIV(Yam)	TIV(Yam)/QIV
B-Yamagata	388	277.6	381	270.7	1.0 (0.81, 1.19)

N = Number of subjects with non-missing data; GMT = Geometric mean titer; GMR = Geometric Mean Ratio.

^aHI titer data of the two trivalent formulations were pooled for the two A-strains.

Note: Adjusted GMR and 95% CI were calculated using analysis of variance on the log-transformed titers at the Day 29/Day 57 visit with age, group, center, priming status included as covariates in the model.

Noninferiority of QIV to TIV could be concluded if for all four strains the upper limit of the 95% CI fell below 1.5.

Table 5. Non-inferiority of QIV versus TIV against shared strains based on post-vaccination geometric mean HI titers – per-protocol sample – study INFQ3001.

	QIV		TIV^a		TIV^a/QIV
Strain	N	GMT	N	GMT	Adjusted GMR (95% CI)
A(H1N1)	1,511	186.6	433	220.9	1.18 (1.023, 1.370)
A(H3N2)	1,524	393.1	436	413.5	1.06 (0.928, 1.213)
		QIV		TIV(Vic)	TIV(Vic)/QIV
B-Victoria	1,521	152.9	215	142.0	0.88 (0.726, 1.071)
		QIV		TIV(Yam)	TIV(Yam)/QIV
B-Yamagata	1,520	102.1	215	86.1	0.82 (0.677, 0.998)

^aHI titer data of the two trivalent formulations were pooled for the two A-strains.

Note: Adjusted GMR and 95% CI were calculated using analysis of variance on the log-transformed titers at the Day 22 visit with age group, country, center, and vaccine group included as factors in the model.

Noninferiority of QIV to TIV could be concluded if for all four strains the upper limit of the 95% CI fell below 1.5.