Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028)

Figures & data

Table 1. Patient demographic and baseline characteristics (all randomized).

	V114-SC	V114-IM	PCV13-SC	Total
Participants in population, n	44	45	44	133
Gender, n (%)
Male	24 (54.5)	27 (60.0)	24 (54.5)	75 (56.4)
Female	20 (45.5)	18 (40.0)	20 (45.5)	58 (43.6)
Age, n (%)
12 weeks	1 (2.3)	1 (2.2)	1 (2.3)	3 (2.3)
13 weeks	20 (45.5)	17 (37.8)	23 (52.3)	60 (45.1)
14 weeks	13 (29.5)	18 (40.0)	11 (25.0)	42 (31.6)
15 weeks	10 (22.7)	4 (8.9)	4 (9.1)	18 (13.5)
16 weeks	0 (0.0)	5 (11.1)	5 (11.4)	10 (7.5)
Age, months
Mean	13.7	13.9	13.8	13.8
SD	0.8	1.0	1.1	1.0
Median	14.0	14.0	13.0	14.0
Range	12–15	12–16	12–16	12–16
Weight (kg)
Subjects with data, n	44	45	43	132
Mean	6.46	6.43	6.34	6.41
SD	0.84	0.87	0.71	0.80
Median	6.45	6.40	6.60	6.45
Range	4.9–8.6	4.7–8.6	5.1–7.8	4.7–8.6

IM: intramuscular; PCV13: 13-valent pneumococcal conjugate vaccine; SC: subcutaneous; SD: standard deviation; V114: 15-valent pneumococcal conjugate vaccine.

Table 2. Summary of AEs.

n (%)	V114-SC	V114-IM	PCV13-SC	Total
Number of participants with AEs in the APaT population throughout the study
Participants in population with follow-up	44	45	44	132
With ≥1 AE	44 (100.0)	44 (97.8)	43 (100.0)	131 (99.2)
Injection site	44 (100.0)	40 (88.9)	43 (100.0)	127 (96.6)
Non-injection site	43 (97.7)	43 (95.6)	42 (97.7)	128 (97.0)
With no AE	0 (0.0)	1 (2.2)	0 (0.0)	1 (0.8)
With vaccine-related AEs^†	44 (100.0)	43 (95.6)	43 (100.0)	130 (98.5)
Injection site	44 (100.0)	40 (88.9)	43 (100.0)	127 (96.2)
Non-injection site	37 (84.1)	37 (82.2)	36 (83.7)	110 (83.3)
With SAEs	1 (2.3)	3 (6.7)	2 (4.7)	6 (4.5)
With vaccine-related SAEs	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Deaths	0 (0.0)	1 (2.2)	0 (0.0)	1 (0.8)
Discontinuation due to an AE	0 (0.0)	1 (2.2)	0 (0.0)	1 (0.8)
Discontinuation due to a vaccine-related AE	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Discontinuation due to an SAE	0 (0.0)	1 (2.2)	0 (0.0)	1 (0.8)
Discontinuation due to a vaccine-related SAE	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)

^†Determined by the investigator to be related to the vaccine.

AE: adverse event; APaT: all-participants-as-treated; IM: intramuscular; PCV13: 13-valent pneumococcal conjugate vaccine; SAE: serious adverse event; SC: subcutaneous; V114: 15-valent pneumococcal conjugate vaccine.

Table 3. Analysis of maximum temperatures on days 1–7 following any vaccination.

Vaccination	n (%)			Difference in V114-IM estimate, % (95% CI)^†	Difference in PCV13-SC estimate, % (95% CI)^†
Participants with temperature data (days 1–7)
V114-SC		44 (100.0)	0.0 (−8.1, 7.9)			0.0 (−8.1, 8.3)
V114-IM		45 (100.0)				0.0 (−7.9, 8.3)
PCV13-SC		43 (100.0)
Maximum temperature (axillary or axillary equivalent)
Maximum temperature ≥37.5°C (99.5°F)
V114-SC		29 (65.9)	5.9 (−14.2, 25.5)			−10.8 (−29.4, 9.4)
V114-IM		27 (60.0)				−16.7 (−35.2, 2.9)
PCV13-SC		33 (76.7)
Maximum temperature ≥38.0°C (100.4°F)
V114-SC		17 (38.6)	7.5 (−12.3, 26.9)			−5.5 (−25.7, 15.1)
V114-IM		14 (31.1)				−13.1 (−32.5, 7.2)
PCV13-SC		19 (44.2)
Maximum temperature ≥39.0°C (102.2°F)
V114-SC		2 (4.5)	−2.1 (−14.1, 9.5)			2.2 (−8.1, 13.2)
V114-IM		3 (6.7)				4.3 (−6.3, 16.0)
PCV13-SC		1 (2.3)
Maximum temperature ≥40.0°C (104.0°F)
V114-SC		1 (2.3)	2.3 (−5.8, 11.9)			−0.1 (−10.1, 9.8)
V114-IM		0 (0.0)				−2.3 (−12.1, 5.7)
PCV13-SC		1 (2.3)

Percentages for the maximum temperature categories are calculated based on the number of subjects with temperature data. Multiple occurrences of maximum temperature are counted only once. Non-axillary temperatures have been converted to axillary equivalent.

^†Based on the Miettinen and Nurminen method.

CI: confidence interval; IM: intramuscular; PCV13: 13-valent pneumococcal conjugate vaccine; SC: subcutaneous; V114: 15-valent pneumococcal conjugate vaccine.

Table 4. Analysis of IgG antibody response rates (% ≥0.35 μg/mL) at 1-month PD3 (PP population).

Pneumococcal serotype	V114-SC (N = 44)		V114-IM (N = 45)		PCV13-SC (N = 43)
	Observed response % (m/n)	95% CI^†	Observed response % (m/n)	95% CI^†	Observed response % (m/n)	95% CI^†
1	100.0 (44/44)	91.96, 100.00	100.0 (45/45)	92.13, 100.00	100.0 (42/42)	91.59, 100.00
3	100.0 (44/44)	91.96, 100.00	97.8 (44/45)	88.23, 99.94	100.0 (42/42)	91.59, 100.00
4	100.0 (44/44)	91.96, 100.00	100.0 (45/45)	92.13, 100.00	100.0 (42/42)	91.59, 100.00
5	100.0 (44/44)	91.96, 100.00	100.0 (45/45)	92.13, 100.00	100.0 (42/42)	91.59, 100.00
6A	97.7 (43/44)	87.98, 99.94	100.0 (45/45)	92.13, 100.00	100.0 (42/42)	91.59, 100.00
6B	90.9 (40/44)	78.33, 97.47	93.3 (42/45)	81.73, 98.60	100.0 (42/42)	91.59, 100.00
7F	100.0 (44/44)	91.96, 100.00	97.8 (44/45)	88.23, 99.94	100.0 (42/42)	91.59, 100.00
9V	100.0 (44/44)	91.96, 100.00	100.0 (45/45)	92.13, 100.00	100.0 (42/42)	91.59, 100.00
14	97.7 (43/44)	87.98, 99.94	100.0 (45/45)	92.13, 100.00	100.0 (42/42)	91.59, 100.00
18C	100.0 (44/44)	91.96, 100.00	100.0 (45/45)	92.13, 100.00	100.0 (42/42)	91.59, 100.00
19A	100.0 (44/44)	91.96, 100.00	100.0 (45/45)	92.13, 100.00	100.0 (42/42)	91.59, 100.00
19F	100.0 (44/44)	91.96, 100.00	100.0 (45/45)	92.13, 100.00	100.0 (42/42)	91.59, 100.00
23F	97.7 (43/44)	87.98, 99.94	100.0 (45/45)	92.13, 100.00	97.6 (41/42)	87.43, 99.94
22F	95.5 (42/44)	84.53, 99.44	100.0 (45/45)	92.13, 100.00	4.8 (2/42)	0.58, 16.16
33F	81.8 (36/44)	67.29, 91.81	88.9 (40/45)	75.95, 96.29	0.0 (0/42)	0.00, 8.41

^†The 95% CI is based on the method of Clopper and Pearson.

N = number of subjects randomized and vaccinated.

m = number of subjects with IgG antibody level ≥0.35 μg/mL.

n = number of subjects contributing to the analysis.

CI: confidence interval; IgG: immunoglobulin G; IM: intramuscular; PCV13: 13-valent pneumococcal conjugate vaccine; PD3: post-dose 3; PP: per protocol; SC: subcutaneous; V114: 15-valent pneumococcal conjugate vaccine.

Table 5. Analysis of IgG GMCs (μg/mL) at 1-month PD3 (PP population).

Pneumococcal serotype	V114-SC (N = 44)			V114-IM (N = 45)			PCV13-SC (N = 43)
	n	Estimate	95% CI	n	Estimate	95% CI	n	Estimate	95% CI
1	44	4.03	3.33, 4.88	45	4.55	3.76, 5.50	42	5.30	4.36, 6.45
3	44	3.95	3.20, 4.89	45	4.52	3.66, 5.57	42	3.04	2.44, 3.78
4	44	5.40	4.63, 6.29	45	6.02	5.17, 7.01	42	7.48	6.39, 8.75
5	44	3.51	2.80, 4.40	45	3.98	3.19, 4.98	42	4.20	3.33, 5.29
6A	44	2.09	1.70, 2.57	45	2.30	1.88, 2.82	42	3.33	2.69, 4.11
6B	44	1.51	1.14, 1.99	45	1.72	1.31, 2.27	42	2.85	2.14, 3.78
7F	44	2.95	2.42, 3.59	45	3.32	2.73, 4.03	42	4.85	3.97, 5.94
9V	44	4.18	3.45, 5.06	45	4.75	3.93, 5.74	42	5.54	4.55, 6.74
14	44	11.43	8.99, 14.53	45	13.79	10.87, 17.48	42	13.54	10.59, 17.31
18C	44	3.10	2.58, 3.72	45	3.17	2.64, 3.80	42	4.48	3.72, 5.41
19A	44	6.27	5.15, 7.63	45	5.25	4.33, 6.38	42	7.22	5.90, 8.83
19F	44	5.42	4.65, 6.32	45	5.85	5.02, 6.80	42	7.62	6.51, 8.92
23F	44	2.56	2.04, 3.20	45	2.57	2.06, 3.21	42	3.24	2.57, 4.07
22F	44	6.82	5.10, 9.13	45	10.35	7.76, 13.80	42	0.05	0.04, 0.07
33F	44	1.15	0.81, 1.62	45	1.56	1.11, 2.19	42	0.05	0.03, 0.06

N = number of subjects randomized and vaccinated.

n = number of subjects contributing to the analysis.

CI: confidence interval; IgG: immunoglobulin G; IM: intramuscular; PCV13: 13-valent pneumococcal conjugate vaccine; PD3: post-dose 3; PP: per protocol; SC: subcutaneous; V114: 15-valent pneumococcal conjugate vaccine.