Immunogenicity and safety of the diphtheria, pertussis, tetanus and inactivated poliovirus vaccine when co-administered with the human rotavirus vaccine (Rotarix) in healthy Japanese infants: a phase IV randomized study

Figures & data

Table 1. Demographics of subjects at baseline, total vaccinated cohort (TVC).

Characteristics		Group 1 Co-administered N = 147		Group 2 Staggered N = 145
Gender (n, %)	Female	72	(49.0)	65	(44.8)
	Male	75	(51.0)	80	(55.2)
Geographical ancestry (n, %)	Asian – Japanese Heritage	147	(100)	145	(100)
Age at each vaccine dose (weeks)
Dose 1 of HRV	Mean (SD)	9.5	(1.1)	9.4	(1.1)
Dose 2 of HRV	Mean (SD)	14.0	(1.1)	15.5	(1.3)
Dose 1 of DPT-IPV	N	147		144
	Mean (SD)	14.0	(1.1)	13.9	(1.0)
Dose 2 of DPT-IPV	N	146		144
	Mean (SD)	18.5	(1.2)	20.0	(1.4)
Dose 3 of DPT-IPV	N	146		144
	Mean (SD)	23.7	(1.8)	25.0	(1.9)
Weight (kg)	Mean (SD)	5.6	(0.7)	5.5	(0.7)
BMI (kg/m^2)	Mean (SD)	16.5	(1.5)	16.6	(1.6)
Gestational age (weeks)	Mean (SD)	39.1	(1.1)	38.8	(1.1)

N/n = number of subjects; BMI: Body mass index; DPT-IPV, diphtheria-pertussis-tetanus and inactivated polio vaccine; HRV, human rotavirus vaccine; SD: Standard deviation

Figure 1. Study Flow.

ATP, according-to-protocol cohort; N, number of individuals in the cohorts; n, number of individuals discontinued or excluded

Table 2. Seroprotection rates (SPR) for diphtheria toxin, tetanus toxin, and polio virus type 1, 2 and 3 and seropositivity rates for pertussis (PT, FHA) for co-administered and staggered groups at one month following the third dose of DPT-IPV vaccine (ATP cohort for immunogenicity).

		Group 1 Co-administered		Group 2 Staggered		Estimated difference (Co-administered minus Staggered)
Antigens/toxin	Threshold levels	N	SPR % (n/N)	N	SPR % (n/N)	%	95% CI
Diphtheria Toxin	≥0.1 IU/mL	141	100	137	100	0.00	−2.66	2.74
Tetanus Toxin	≥0.1 IU/mL	141	98.6	138	99.3	−0.69	−4.39	2.71
Pertussis FHA	≥10 IU/mL	141	100	138	100	0.00	−2.66	2.72
Pertussis PT	≥10 IU/mL	141	95.7	138	92.8	2.99	−2.70	9.12
Poliovirus Type 1	NAT ≥ 8 ED50	140	100	137	100	0.00	−2.68	2.74
Poliovirus Type 2	NAT ≥ 8 ED50	128	100	127	100	0.00	−2.92	2.95
Poliovirus Type 3	NAT ≥ 8 ED50	132	100	123	99.2	0.81	−2.04	4.47

ATP, according to protocol; CI, Confidence interval; DPT-IPV, diphtheria-pertussis-tetanus and inactivated polio vaccine; ED₅₀, 50% effective dose; FHA, pertussis filamentous hemagglutinin; n, Number of subjects who achieved the seroprotection/seropositivity threshold; N, Number of subjects in the ATP cohort for immunogenicity analyses; NAT, Neutralizing antibody titers; PT, pertussis toxin; SPR: Seroprotection/seropositivity rate.

Table 3. Geometric mean titers (GMTs) and concentrations (GMCs) for diphtheria toxin, tetanus toxin, pertussis (PT, FHA), and polio virus type 1, 2 and 3 for co-administered and staggered groups at one month following the third dose of DPT-IPV vaccine (ATP cohort for immunogenicity).

	Group 1 Co-administered				Group 2 Staggered
Antigens/toxin	N	GMC or GMT	95% CI		N	GMC or GMT	95% CI
Diphtheria Toxin	141	5.4	4.9	6.0	137	6.0	5.5	6.6
Tetanus Toxin	141	1.6	1.3	2.0	138	2.0	1.7	2.4
Pertussis FHA	141	83.7	74.8	93.6	138	97.2	86.7	109.0
Pertussis PT	141	31.5	28.4	34.9	138	31.5	27.9	35.6
Poliovirus Type 1	140	404.7	341.4	479.8	137	427.9	359.3	509.6
Poliovirus Type 2	128	371.0	307.0	448.5	127	470.6	388.3	570.3
Poliovirus Type 3	132	436.3	365.6	520.7	123	409.8	330.8	507.5

ATP, according to protocol; CI, Confidence interval; DPT-IPV, diphtheria-pertussis-tetanus and inactivated polio vaccine; ED₅₀, 50% effective dose; FHA, pertussis filamentous hemagglutinin; GMC, Geometric mean concentration; GMT, Geometric mean titer; N, Number of subjects in the ATP cohort for immunogenicity analyses; PT, pertussis toxin.

Table 4. Summary of adverse events, total vaccinated cohort (TVC).

		Group 1 Co-administered		Group 2 Staggered
		n/N	%	n/N	%
AEs (solicited and unsolicited) during the 8-day post-vaccination period following HRV vaccine	Dose 1	102/147	69.4	104/145	71.7
	Dose 2	115/147	78.2	89/145	61.4
	Overall/subject	128/147	87.1	124/145	85.5
AEs (solicited and unsolicited) during the 8-day post-vaccination period following DPT-IPV vaccine	Dose 1	131/147	89.1	124/144	86.1
Unsolicited AEs within the 31-day post-vaccination period following HRV vaccine	Any dose	88/147	59.9	81/145	55.9
Unsolicited AEs within the 31-day post-vaccination period following first dose of DPT-IPV vaccine	Dose 1	65/147	44.2	59/144	41.0
At least one SAE		4/147	2.7	5/145	3.4
At least one vaccine-related SAE		0/147	0.0	0/145	0.0
Death		0/147	0.0	0/145	0.0
Discontinuation due to AEs		0/147	0.0	0/145	0.0

AE, Adverse event; DPT-IPV, diphtheria-pertussis-tetanus and inactivated polio vaccine; HRV, Human rotavirus vaccine; N, Number of subjects; n: number of subjects reporting an AE; %: percentage of subjects reporting an AE; SAE, Serious adverse event; TVC: total vaccinated cohort.

Figure 2. Focus on the patient.

Figure 3. Vaccination schedule in the co-administered group and staggered group.

, blood sample;

DPT-IPV vaccine, diphtheria-pertussis-tetanus and inactivated polio vaccine;

HRV vaccine: oral human rotavirus vaccine

Figure 4. Hierarchical procedure to test the primary confirmatory objective.

ED₅₀, 50% effective dose; FHA, pertussis filamentous hemagglutinin; IU/mL, international unit per milliliter; PT, pertussis toxin. ^†In terms of percentages of subjects with concentrations ≥10 IU/mL for anti-PT and anti-FHA, seroprotective concentrations for anti-D and anti-T or seroprotective titers for anti-IPV1, 2 and 3 at Visit 7 using a nominal alpha risk of 2.5%.ED₅₀