Immunogenicity and safety of a nine-valent human papillomavirus vaccine in Vietnamese males and females (9 to 26 years of age): an open-label, phase 3 trial

Figures & data

Table 1. Participant baseline demographics and characteristics

	Total participants (N = 201)
Age
Mean (SD), years	15.8 (4.4)
Median (range), years	15.0 (9–26)
9 to 12 years, n (%)	50 (24.9)
13 to 15 years, n (%)	51 (25.4)
16 to 26 years, n (%)	100 (49.8)
Gender, n (%)
Female	135 (67.2)
Male	66 (32.8)
Height, cm
Mean (SD)	155.22 (10.86)
Median (range)	157.00 (120–177)
Weight, kg
Mean (SD)	48.21 (11.69)
Median (range)	47.50 (25–92)
Sexual history at Day 1,^a n (%)
Has not had sexual debut	91 (91.0)
Has had sexual debut	9 (9.0)
Age at first sexual intercourse among non-virgins,^b years
Mean (SD)	20.3 (2.3)
Median (range)	21.0 (16–23)
Lifetime number of male or female sexual partners among non-virgins,^b n (%)
1	8 (8.0)
3	1 (1.0)
Median	1
HPV seropositivity status at Day 1, n (%)
Anti-HPV6	4 (2.0)
Anti-HPV11	1 (0.5)
Anti-HPV16	8 (4.0)
Anti-HPV18	5 (2.5)
Anti-HPV31	7 (3.5)
Anti-HPV33	1 (0.5)
Anti-HPV45	2 (1.0)
Anti-HPV52	3 (1.5)
Anti-HPV58	5 (2.5)

^aSexual history was collected from participants 16 to 26 years of age only (N = 100).

^b9 participants were non-virgins period

cm, centimeters; HPV, human papillomavirus; kg, kilograms; SD, standard deviation.

Figure 1. Participant disposition. ^aOne participant discontinued due to a protocol deviation (the participant was randomized in error [failed to satisfy eligibility criteria] and was discontinued from the study prior to receiving the first 9vHPV vaccine dose) and two participants withdrew consent. 9vHPV, nine-valent human papillomavirus

Table 2. Summary of anti-HPV seroconversion percentages and GMTs at Month 7 in the Vietnam registration study and historic seroconversion percentages and GMTs at Month 7 in the pivotal efficacy study of the 9vHPV vaccine (PPI population)

Registration study of 9vHPV vaccine in Vietnam
Assay (cLIA)	Study population	N	n	% seroconversion (95% CI)^a	GMT (95% CI)^b
Anti-HPV6	All participants	200	190	100 (98.1–100)	1008.2 (921.9–1102.6)
	Participants 9–15 years of age	100	98	100 (96.3–100)	1203.1 (1076.0–1345.2)
	Participants 16–26 years of age	100	92	100 (96.1–100)	835.2 (731.1–954.1)
Anti-HPV11	All participants	200	190	100 (98.1–100)	796.3 (722.2–878.0)
	Participants 9–15 years of age	100	98	100 (96.3–100)	970.1 (863.2–1090.2)
	Participants 16–26 years of age	100	92	100 (96.1–100)	645.3 (555.8–749.2)
Anti-HPV16	All participants	200	187	100 (98.0–100)	4605.4 (4163.7–5093.9)
	Participants 9–15 years of age	100	98	100 (96.3–100)	5579.0 (4915.4–6332.1)
	Participants 16–26 years of age	100	89	100 (95.9–100)	3728.7 (3209.6–4331.7)
Anti-HPV18	All participants	200	190	100 (98.1–100)	1621.6 (1441.2–1824.5)
	Participants 9–15 years of age	100	98	100 (96.3–100)	2115.1 (1833.9–2439.3)
	Participants 16–26 years of age	100	92	100 (96.1–100)	1221.8 (1025.7–1455.4)
Anti-HPV31	All participants	200	188	100 (98.1–100)	1137.9 (1017.2–1273.0)
	Participants 9–15 years of age	100	97	100 (96.3–100)	1458.4 (1271.2–1673.2)
	Participants 16–26 years of age	100	91	100 (96.0–100)	873.5 (740.5–1030.4)
Anti-HPV33	All participants	200	194	100 (98.1–100)	507.8 (458.5–562.4)
	Participants 9–15 years of age	100	100	100 (96.4–100)	641.2 (564.2–728.6)
	Participants 16–26 years of age	100	94	100 (96.2–100)	396.2 (342.0–459.0)
Anti-HPV45	All participants	200	193	100 (98.1–100)	579.2 (511.7–655.6)
	Participants 9–15 years of age	100	99	100 (96.3–100)	752.4 (636.3–889.7)
	Participants 16–26 years of age	100	94	100 (96.2–100)	439.7 (371.4–520.5)
Anti-HPV52	All participants	200	192	100 (98.1–100)	500.8 (450.5–556.7)
	Participants 9–15 years of age	100	100	100 (96.4–100)	632.4 (551.0–725.8)
	Participants 16–26 years of age	100	92	100 (96.1–100)	388.6 (335.2–450.6)
Anti-HPV58	All participants	200	190	100 (98.1–100)	701.8 (628.5–783.7)
	Participants 9–15 years of age	100	98	100 (96.3–100)	888.9 (771.3–1024.5)
	Participants 16–26 years of age	100	92	100 (96.1–100)	545.6 (466.3–638.6)
Historic results from the pivotal efficacy study of the 9vHPV vaccine (9vHPV vaccine arm)^c
Assay (cLIA)	Study population	N	n	% seroconversion (95% CI)^a	GMT (95% CI)^b
Anti-HPV6	Participants 16–26 years of age	6792	3993	99.8 (99.6–99.9)	893.1 (871.7–915.1)
Anti-HPV11	Participants 16–26 years of age	6792	3995	100 (99.9–100)	666.3 (649.6–683.4)
Anti-HPV16	Participants 16–26 years of age	6792	4032	100 (99.9–100)	3131.1 (3057.1–3206.9)
Anti-HPV18	Participants 16–26 years of age	6792	4539	99.8 (99.7–99.9)	804.6 (782.7–827.1)
Anti-HPV31	Participants 16–26 years of age	6792	4466	99.8 (99.6–99.9)	658.4 (636.7–680.9)
Anti-HPV33	Participants 16–26 years of age	6792	4702	99.7 (99.5–99.9)	415.9 (405.6–426.4)
Anti-HPV45	Participants 16–26 years of age	6792	4792	99.6 (99.4–99.8)	252.8 (246.2–259.6)
Anti-HPV52	Participants 16–26 years of age	6792	4455	99.8 (99.6–99.9)	379.7 (371.6–388.0)
Anti-HPV58	Participants 16–26 years of age	6792	4486	99.8 (99.6–99.9)	482.5 (469.9–495.3)

N = number of participants who received at least one 9vHPV vaccine dose.

n = number of participants contributing to the analysis.

^aSeroconversion = 100*(number of participants who seroconverted/number of participants included in the analysis).

^bUnits in mMU/mL.

^cResults from Huh et al.¹⁴

The PPI population included participants who received three vaccinations within acceptable day ranges, were seronegative at Day 1 for the relevant HPV type(s), provided a serum sample within 21 to 49 days post-Dose 3, and had no protocol violations that could interfere with the immunogenicity evaluation. In addition, for the PPI population in the historic pivotal efficacy study, participants also had to be PCR-negative from Day 1 to Month 7 for the relevant HPV type(s).

9vHPV, nine-valent human papillomavirus; CI, confidence interval; cLIA, competitive Luminex immunoassay; GMT, geometric mean titer; HPV, human papillomavirus; PCR, polymerase chain reaction; PPI, per-protocol immunogenicity; mMU, milli-Merck unit.

Table 3. AE summary (‘all participants as treated’ population)

	9vHPV vaccine (N = 200)
Participants with ≥1 AE, n (%)^a	101 (50.5)
Injection-site AEs, n (%)^b	90 (45.0)
Injection-site pain	89 (44.5)
Mild	86 (43.0)
Moderate	3 (1.5)
Injection-site swelling	11 (5.5)
Mild (0 to 2.5 cm)	9 (4.5)
Moderate (2.5 to 5.0 cm)	1 (0.5)
Severe (>5.0 cm)	1 (0.5)
Injection-site erythema	4 (2.0)
Mild (0 to 2.5 cm)	4 (2.0)
Systemic AEs, n (%)^c	34 (17.0)
Headache	7 (3.5)
Dizziness	5 (2.5)
Nasopharyngitis	5 (2.5)
Vaccine-related^d systemic AEs, n (%)^c	2 (1.0)
SAEs, n (%)^a	1 (0.5)
Vaccine-related^d SAEs, n (%)	0 (0.0)
Deaths, n (%)	0 (0.0)
Participants who discontinued^e due to an AE,^a n (%)	0 (0.0)
Maximum temperature (oral) <37.8°C^b	200 (100)

N = number of participants who had ≥1 dose of the 9vHPV vaccine and had ≥1 follow-up visit for an AE.

^aAt any time during the study.

^bDays 1 to 5 following any vaccination.

^cDays 1 to 15 following any vaccination.

^dAs determined by the reporting investigator.

^eStudy vaccination withdrawn.

Injection-site and systemic AEs shown are those with a frequency ≥2%. Participants were counted once for each applicable AE.

9vHPV, nine-valent human papillomavirus; AE, adverse event; SAE, serious adverse event.

Huh WK, Joura EA, Giuliano AR, Iversen O-E, de Andrade RP, Ault KA, Bartholomew D, Cestero RM, Fedrizzi EN, Hirschberg AL, et al. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16–26 years: a randomised, double-blind trial. Lancet. 2017;390(10108):2143–59. doi:10.1016/S0140-6736(17)31821-4.

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