A Study of V503 (A Multivalent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] Vaccine) in Preadolescents and Adolescents (V503-002)

• ClinicalTrials.gov Identifier: NCT00943722
• Recruitment Status: Completed
• First Posted: July 22, 2009
• Results First Posted: January 13, 2015
• Last Update Posted: October 3, 2022
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Conditions: Cervical Cancers; Vulvar Cancer; Vaginal Cancer; Genital Lesions; PAP Test Abnormalities; HPV Infections
• Intervention: Biological: V503
• Enrollment: 3074

Participant Flow

Recruitment Details

The base study was a 12-month study that collected immunogenicity data through Month 7 and safety data through Month 12.

Pre-assignment Details

Extension study 1 (EXT1) collected data to Month 36. Extension study 2 (EXT2) collected long-term data through ~Month 126. No study vaccine was administered. Per protocol, participants enrolled in the 16- to 26-year-old arm in the base study were not included in the extension study. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered (arm: "Extension Study: 9- to 15- Year Old Females").

Arm/Group Title	Base Study: 9- to 15-Year-Old Females (Lot 1)	Base Study: 9- to 15-Year-Old Females (Lot 2)	Base Study: 9- to 15-Year-Old Females (Lot 3)	Base Study: 9- to 15-Year-Old Males (Lot 1)	Base Study: 16- to 26-Year-Old Females (Lot 1)	Extension Study: 9- to 15-Year-Old Females	Extension Study: 9- to 15-Year-Old Males
Arm/Group Description	9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 2.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 3.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).	In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2)
Period Title: Base Study
Started	648	643	644	669	470	0	0
Vaccination 1	646	642	644	666	468	0	0
Vaccination 2	637	633	638	658	462	0	0
Vaccination 3	635	627	637	653	455	0	0
At Least One Dose With Protocol-specified Safety Follow-up	643	639	641	662	466	0	0
Completed	623	621	631	647	444	0	0
Not Completed	25	22	13	22	26	0	0
Reason Not Completed
Adverse Event	0	0	0	1	0	0	0
Lost to Follow-up	12	8	10	8	11	0	0
Physician Decision	1	0	0	0	1	0	0
Pregnancy	0	0	1	0	2	0	0
Protocol Violation	0	1	0	0	2	0	0
Withdrawal by Subject	12	13	2	13	8	0	0
Month 12 visit not completed	0	0	0	0	2	0	0
Period Title: First Extension Study: EXT 1
Started [1]	0	0	0	0	0	1604	568
Completed	0	0	0	0	0	1489	527
Not Completed	0	0	0	0	0	115	41
Reason Not Completed
Adverse Event	0	0	0	0	0	1	0
Lost to Follow-up	0	0	0	0	0	38	10
Withdrawal by Subject	0	0	0	0	0	32	10
Disposition Unknown	0	0	0	0	0	44	21
[1] The optional EXT1 included eligible participants from the base study, with the exception of 16-26 year old females.
Period Title: Second Extension Study: EXT 2
Started [1]	0	0	0	0	0	971	301
Completed	0	0	0	0	0	720	202
Not Completed	0	0	0	0	0	251	99
Reason Not Completed
Adverse Event	0	0	0	0	0	1	0
Lost to Follow-up	0	0	0	0	0	111	46
Physician Decision	0	0	0	0	0	1	3
Pregnancy	0	0	0	0	0	1	0
Withdrawal by Subject	0	0	0	0	0	137	50
[1] The optional EXT2 included eligible participants from the base study, with the exception of 16-26 year old females.

Baseline Characteristics

Arm/Group Title		Base Study: 9- to 15-Year-Old Females (Lot 1)	Base Study: 9- to 15-Year-Old Females (Lot 2)	Base Study: 9- to 15-Year-Old Females (Lot 3)	Base Study: 9- to 15-Year-Old Males (Lot 1)	Base Study: 16- to 26-Year-Old Females (Lot 1)	Total
Arm/Group Description		9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 2.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 3.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	Total of all reporting groups
Overall Number of Baseline Participants		648	643	644	669	470	3074
Baseline Analysis Population Description		Per protocol, baseline characteristics were analyzed in all participants randomized in the base study.
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	648 participants	643 participants	644 participants	669 participants	470 participants	3074 participants
9 to 12 years		440	432	432	450	0	1754
13 to 15 years		208	211	212	219	0	850
16 to 26 years		0	0	0	0	470	470
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	648 participants	643 participants	644 participants	669 participants	470 participants	3074 participants
	Female	648 100.0%	643 100.0%	644 100.0%	0 0.0%	470 100.0%	2405 78.2%
	Male	0 0.0%	0 0.0%	0 0.0%	669 100.0%	0 0.0%	669 21.8%

Outcome Measures

1. Primary Outcome

Title	Base Study: Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Females [Lot 1] and 16- to 26-Year-Old Females [Lot 1])
Description	Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using a competitive luminex immunoassay (cLIA). Titers were reported in milli Merck Units/mL.
Time Frame	4 weeks post-vaccination 3 (Month 7)

Outcome Measure Data

Analysis Population Description

9-15-year-old females and 16-26-year-old females who received 3 vaccinations from Lot 1 and met following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range.

Arm/Group Title		Base Study: 9- to 15-Year-Old Females (Lot 1)	Base Study: 9- to 15-Year-Old Males (Lot 1)
Arm/Group Description:		9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed		535	378
Geometric Mean (95% Confidence Interval); Unit of Measure: milli Merck Units/mL
Anti-HPV 6	Number Analyzed	517 participants	328 participants
		1715.4; (1595.1 to 1844.7)	900.8; (822.3 to 986.9)
Anti-HPV 11	Number Analyzed	517 participants	332 participants
		1295.1; (1204.1 to 1393.0)	706.6; (645.2 to 773.8)
Anti-HPV 16	Number Analyzed	529 participants	329 participants
		6979.8; (6508.1 to 7485.8)	3522.6; (3223.5 to 3849.5)
Anti-HPV 18	Number Analyzed	531 participants	345 participants
		2153.7; (1980.4 to 2342.1)	882.7; (795.4 to 979.5)
Anti-HPV 31	Number Analyzed	522 participants	340 participants
		1891.6; (1745.7 to 2049.7)	753.9; (682.5 to 832.7)
Anti-HPV 33	Number Analyzed	534 participants	354 participants
		980.4; (911.7 to 1054.3)	466.8; (426.9 to 510.3)
Anti-HPV 45	Number Analyzed	534 participants	368 participants
		714.4; (651.9 to 782.8)	272.2; (243.8 to 303.9)
Anti-HPV 52	Number Analyzed	533 participants	337 participants
		932.9; (864.8 to 1006.4)	419.6; (381.4 to 461.5)
Anti-HPV 58	Number Analyzed	531 participants	332 participants
		1286.7; (1195.7 to 1384.6)	590.5; (538.2 to 647.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 6
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% confidence interval (CI) of GMT ratio be greater than 0.67.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.90
	Confidence Interval	(2-Sided) 95%; 1.70 to 2.14
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 11
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.83
	Confidence Interval	(2-Sided) 95%; 1.63 to 2.06
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 16
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.98
	Confidence Interval	(2-Sided) 95%; 1.77 to 2.22
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 18
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	2.44
	Confidence Interval	(2-Sided) 95%; 2.13 to 2.80
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 31
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	2.51
	Confidence Interval	(2-Sided) 95%; 2.21 to 2.85
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 33
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	2.10
	Confidence Interval	(2-Sided) 95%; 1.87 to 2.36
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 45
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	2.62
	Confidence Interval	(2-Sided) 95%; 2.27 to 3.03
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 52
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	2.22
	Confidence Interval	(2-Sided) 95%; 1.97 to 2.51
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 58
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	2.18
	Confidence Interval	(2-Sided) 95%; 1.93 to 2.45
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

2. Primary Outcome

Title	Base Study: GMTs for Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Males [Lot 1] and 16- to 26-Year-Old Females [Lot 1])
Description	Serum antibody titers for HPV VLPs, Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using a competitive luminex immunoassay (cLIA). Titers were reported in milli Merck Units/mL.
Time Frame	4 weeks post-vaccination 3 (Month 7)

Outcome Measure Data

Analysis Population Description

9-15-year-old males and 16-26-year-old females who received 3 vaccinations from Lot 1 and met following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range.

Arm/Group Title		Base Study: 9- to 15-Year-Old Males (Lot 1)	Base Study: 16- to 26-Year-Old Females (Lot 1)
Arm/Group Description:		9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed		570	378
Geometric Mean (95% Confidence Interval); Unit of Measure: milli Merck Units/mL
Anti-HPV 6	Number Analyzed	559 participants	328 participants
		2084.7; (1944.0 to 2235.7)	900.8; (822.3 to 986.9)
Anti-HPV 11	Number Analyzed	559 participants	332 participants
		1487.1; (1386.5 to 1595.0)	706.6; (645.2 to 773.8)
Anti-HPV 16	Number Analyzed	569 participants	329 participants
		8628.9; (8065.9 to 9231.3)	3522.6; (3223.5 to 3849.5)
Anti-HPV 18	Number Analyzed	567 participants	345 participants
		2822.8; (2602.8 to 3061.5)	882.7; (795.4 to 979.5)
Anti-HPV 31	Number Analyzed	564 participants	340 participants
		2221.2; (2056.1 to 2399.5)	753.9; (682.5 to 832.7)
Anti-HPV 33	Number Analyzed	567 participants	354 participants
		1198.7; (1117.1 to 1286.2)	466.8; (426.9 to 510.3)
Anti-HPV 45	Number Analyzed	570 participants	368 participants
		907.0; (830.2 to 991.0)	272.2; (243.8 to 303.9)
Anti-HPV 52	Number Analyzed	568 participants	337 participants
		1037.8; (964.4 to 1116.9)	419.6; (381.4 to 461.5)
Anti-HPV 58	Number Analyzed	566 participants	332 participants
		1567.7; (1460.2 to 1683.1)	590.5; (538.2 to 647.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 6
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	2.31
	Confidence Interval	(2-Sided) 95%; 2.07 to 2.59
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 11
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	2.10
	Confidence Interval	(2-Sided) 95%; 1.88 to 2.36
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 16
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	2.45
	Confidence Interval	(2-Sided) 95%; 2.19 to 2.74
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 18
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	3.20
	Confidence Interval	(2-Sided) 95%; 2.80 to 3.65
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 31
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	2.95
	Confidence Interval	(2-Sided) 95%; 2.60 to 3.34
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 33
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	2.57
	Confidence Interval	(2-Sided) 95%; 2.29 to 2.88
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 45
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	3.33
	Confidence Interval	(2-Sided) 95%; 2.89 to 3.84
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 52
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	2.47
	Confidence Interval	(2-Sided) 95%; 2.19 to 2.79
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 58
	Type of Statistical Test	Non-Inferiority
	Comments	non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
	Method	ANOVA
	Comments	model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	2.66
	Confidence Interval	(2-Sided) 95%; 2.37 to 2.98
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)

3. Primary Outcome

Title	Base Study: GMTs for Each of the HPV Types Contained in the Vaccine (Lot Consistency Study)
Description	Serum antibody titers for HPV VLPs, Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using cLIA. Titers were reported in milli Merck Units/mL.
Time Frame	4 weeks post-vaccination 3 (Month 7)

Outcome Measure Data

Analysis Population Description

9-15-year-old females who received 3 vaccinations from Lots 1, 2, or 3 and met following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range.

Arm/Group Title		Base Study: 9- to 15-Year-Old Females (Lot 1)	Base Study: 9- to 15-Year-Old Females (Lot 2)	Base Study: 9- to 15-Year-Old Females (Lot 3)
Arm/Group Description:		9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 2.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 3.
Overall Number of Participants Analyzed		535	549	565
Geometric Mean (95% Confidence Interval); Unit of Measure: milli Merck Units/mL
Anti-HPV 6	Number Analyzed	517 participants	536 participants	544 participants
		1715.4; (1588.7 to 1852.2)	1763.3; (1635.4 to 1901.3)	1659.9; (1540.3 to 1788.7)
Anti-HPV 11	Number Analyzed	517 participants	536 participants	544 participants
		1295.1; (1197.8 to 1400.3)	1311.7; (1214.9 to 1416.3)	1232.0; (1141.7 to 1329.5)
Anti-HPV 16	Number Analyzed	529 participants	542 participants	556 participants
		6979.8; (6476.1 to 7522.8)	7292.9; (6772.7 to 7853.1)	6948.2; (6458.7 to 7474.9)
Anti-HPV 18	Number Analyzed	531 participants	547 participants	563 participants
		2153.7; (1970.9 to 2353.5)	2134.1; (1955.6 to 2329.0)	1966.6; (1804.3 to 2143.5)
Anti-HPV 31	Number Analyzed	522 participants	542 participants	553 participants
		1891.6; (1738.5 to 2058.2)	1867.8; (1719.3 to 2029.1)	1879.0; (1731.0 to 2039.6)
Anti-HPV 33	Number Analyzed	534 participants	543 participants	560 participants
		980.4; (909.2 to 1057.2)	922.7; (856.2 to 994.4)	931.1; (865.0 to 1002.3)
Anti-HPV 45	Number Analyzed	534 participants	548 participants	565 participants
		714.4; (650.1 to 785.0)	827.7; (754.1 to 908.5)	678.4; (619.0 to 743.6)
Anti-HPV 52	Number Analyzed	533 participants	547 participants	562 participants
		932.9; (860.8 to 1011.0)	1007.9; (931.0 to 1091.2)	971.2; (898.1 to 1050.3)
Anti-HPV 58	Number Analyzed	531 participants	539 participants	560 participants
		1286.7; (1190.0 to 1391.3)	1344.9; (1244.6 to 1453.3)	1208.1; (1119.6 to 1303.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 6
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.08
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 6
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0).
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.93 to 1.16
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 6
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0).
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.95 to 1.19
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 11
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0).
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.11
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 11
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0).
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.95 to 1.20
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 11
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0).
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.95 to 1.20
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 16
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0).
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.06
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 16
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.12
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 16
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.17
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 18
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.14
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 18
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.98 to 1.26
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 18
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.26
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 31
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.13
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 31
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.91 to 1.16
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 31
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.15
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 33
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.16
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 33
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.17
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 33
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.12
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 45
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.73 to 0.95
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 45
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.91 to 1.18
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 45
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 95%; 1.08 to 1.42
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 52
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.03
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 52
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.07
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 52
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.16
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 58
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.06
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 58
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.96 to 1.20
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 58
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 1.00 to 1.26
	Estimation Comments	GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)

4. Primary Outcome

Title	Base Study: Percentage of Participants With Injection Site Adverse Experiences (AEs)
Description	An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine was also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site were recorded.
Time Frame	Up to 5 days after any vaccination

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of 9vHPV vaccine and had available follow-up data. Per protocol, this outcome measure included data from 9- to 15-year-old females regardless of lot administered.

Arm/Group Title	9- to 15-Year-Old Females (Lots 1, 2 or 3)	Base Study: 9- to 15-Year-Old Males (Lot 1)	Base Study: 16- to 26-Year-Old Females (Lot 1)
Arm/Group Description:	9-valent human papillomavirus (9vHPV) L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered is obtained from manufacturing Lots 1, 2, or 3.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed	1923	662	466
Measure Type: Number; Unit of Measure: Percentage of Participants
	81.9	72.8	85.4

5. Primary Outcome

Title	Base Study: Percentage of Participants With Systemic AEs
Description	An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine was also an AE. Systemic AEs were those not categorized as injection-site AEs.
Time Frame	Up to 15 days after any vaccination

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of 9vHPV vaccine and had available follow-up data. Per protocol, this outcome measure included data from 9- to 15-year-old females regardless of lot administered.

Arm/Group Title	9- to 15-Year-Old Females (Lots 1, 2 or 3)	Base Study: 9- to 15-Year-Old Males (Lot 1)	Base Study: 16- to 26-Year-Old Females (Lot 1)
Arm/Group Description:	9-valent human papillomavirus (9vHPV) L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered is obtained from manufacturing Lots 1, 2, or 3.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed	1923	662	466
Measure Type: Number; Unit of Measure: Percentage of Participants
	45.0	41.8	57.1

6. Primary Outcome

Title	Base Study: Percentage of Participants With Body Temperature ≥100.0°F (≥37.8ºC)
Description	Participants collected their oral body temperature in the evening of their vaccination day and at the same time each day thereafter for 4 days. The maximum body temperature obtained within 5 days of any of the 3 vaccinations was recorded. The percentage of participants who had at least 1 oral body temperature reading that was ≥100.0°F (≥37.8ºC) was summarized.
Time Frame	Up to 5 days after any vaccination

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of 9vHPV vaccine and had available follow-up data. Per protocol, this outcome measure included data from 9- to 15-year-old females regardless of lot administered.

Arm/Group Title	9- to 15-Year-Old Females (Lots 1, 2, or 3)	Base Study: 9- to 15-Year-Old Males (Lot 1)	Base Study: 16- to 26-Year-Old Females (Lot 1)
Arm/Group Description:	Multivalent HPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered is obtained from manufacturing Lots 1, 2, or 3.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed	1908	660	463
Measure Type: Number; Unit of Measure: Percentage of Participants
	8.4	10.0	8.4

7. Primary Outcome

Title	Extension Study: GMTs For Each of the HPV Types Contained in the Vaccine
Description	Serum antibody titers (milli Merck Units/mL) measured by cLIA to each of the 9vHPV types were assessed. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.
Time Frame	Up to ~Month 126

Outcome Measure Data

Analysis Population Description

All participants who met the following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range.

Arm/Group Title		Extension Study: 9- to 15-Year-Old Females	Extension Study: 9- to 15-Year-Old Males
Arm/Group Description:		In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).	In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2)
Overall Number of Participants Analyzed		971	301
Geometric Mean (95% Confidence Interval); Unit of Measure: milli Merck Units/mL
Anti-HPV 6	Number Analyzed	341 participants	176 participants
		122.3; (111.1 to 134.7)	129.5; (112.5 to 149.1)
Anti-HPV 11	Number Analyzed	332 participants	169 participants
		80.2; (72.5 to 88.8)	91.0; (78.4 to 105.6)
Anti-HPV 16	Number Analyzed	388 participants	173 participants
		403.0; (357.3 to 454.5)	414.3; (353.8 to 485.3)
Anti-HPV 18	Number Analyzed	347 participants	178 participants
		128.1; (116.7 to 140.7)	148.4; (130.2 to 169.2)
Anti-HPV 31	Number Analyzed	343 participants	177 participants
		108.9; (97.6 to 121.6)	128.6; (111.2 to 148.8)
Anti-HPV 33	Number Analyzed	344 participants	178 participants
		59.2; (53.7 to 65.2)	69.6; (60.7 to 79.7)
Anti-HPV 45	Number Analyzed	325 participants	169 participants
		42.1; (37.7 to 47.1)	49.8; (43.0 to 57.8)
Anti-HPV 52	Number Analyzed	348 participants	176 participants
		55.3; (50.5 to 60.6)	59.6; (52.0 to 68.4)
Anti-HPV 58	Number Analyzed	342 participants	175 participants
		76.5; (69.2 to 84.6)	90.5; (78.4 to 104.6)

8. Primary Outcome

Title	Extension Study: Percentage of Participants Who Are Seropositive to Each of the HPV Types Contained in the Vaccine
Description	Serum antibody titers for HPV VLPs Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 was determined and reported in milli Merck Units/mL. The percentage of participants seropositive to each HPV type was reported. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.
Time Frame	Up to ~Month 126

Outcome Measure Data

Analysis Population Description

All participants who met the following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range.

Arm/Group Title		Extension Study: 9- to 15-Year-Old Females	Extension Study: 9- to 15-Year-Old Males
Arm/Group Description:		In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).	In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2)
Overall Number of Participants Analyzed		971	301
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Anti-HPV 6	Number Analyzed	341 participants	176 participants
		82.7; (78.3 to 86.6)	84.1; (77.8 to 89.2)
Anti-HPV 11	Number Analyzed	332 participants	169 participants
		85.2; (81.0 to 88.9)	87.0; (81.0 to 91.7)
Anti-HPV 16	Number Analyzed	338 participants	173 participants
		97.3; (95.0 to 98.8)	98.3; (95.0 to 99.6)
Anti-HPV 18	Number Analyzed	347 participants	178 participants
		80.1; (75.5 to 84.2)	83.7; (77.4 to 88.8)
Anti-HPV 31	Number Analyzed	343 participants	177 participants
		90.1; (86.4 to 93.0)	92.7; (87.8 to 96.0)
Anti-HPV 33	Number Analyzed	344 participants	178 participants
		85.2; (81.0 to 88.8)	89.3; (83.8 to 93.4)
Anti-HPV 45	Number Analyzed	325 participants	169 participants
		81.8; (77.2 to 85.9)	92.3; (87.2 to 95.8)
Anti-HPV 52	Number Analyzed	348 participants	176 participants
		88.2; (84.4 to 91.4)	89.2; (83.7 to 93.4)
Anti-HPV 58	Number Analyzed	342 participants	175 participants
		96.5; (94.0 to 98.2)	97.1; (93.5 to 99.1)

9. Secondary Outcome

Title	Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Females [Lot 1] and 16- to 26-Year-Old Females [Lot 1])
Description	Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using cLIA. The serostatus cutoffs (milli Merck U/mL) for HPV types were as follows: HPV Type 6: ≥30, HPV Type 11: ≥16; HPV Type 16: ≥20, HPV Type 18: ≥24, HPV Type 31: ≥10, HPV Type 33: ≥8, HPV Type 45: ≥8, HPV Type 52: ≥8, and HPV Type 58: ≥8.
Time Frame	4 weeks post-vaccination 3 (Month 7)

Outcome Measure Data

Analysis Population Description

9-15-year-old females and 16-26-year-old females who received 3 vaccinations from Lot 1 and met following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range.

Arm/Group Title		Base Study: 9- to 15-Year-Old Females (Lot 1)	Base Study: 9- to 15-Year-Old Males (Lot 1)
Arm/Group Description:		9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed		535	378
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Anti-HPV 6 cLIA ≥30 mMU/mL	Number Analyzed	517 participants	328 participants
		99.8; (98.9 to 100)	99.7; (98.3 to 100)
Anti-HPV 11 cLIA ≥16 mMU/mL	Number Analyzed	517 participants	332 participants
		100; (99.3 to 100.0)	100; (98.9 to 100.0)
Anti-HPV 16 cLIA ≥20 mMU/mL	Number Analyzed	529 participants	329 participants
		100; (99.3 to 100.0)	100; (98.9 to 100.0)
Anti-HPV 18 cLIA ≥24 mMU/mL	Number Analyzed	531 participants	345 participants
		99.8; (99.0 to 100.0)	99.7; (98.4 to 100.0)
Anti-HPV 31 cLIA ≥10 mMU/mL	Number Analyzed	522 participants	340 participants
		100.0; (99.3 to 100.0)	99.7; (98.4 to 100.0)
Anti-HPV 33 cLIA ≥8 mMU/mL	Number Analyzed	534 participants	354 participants
		100.0; (99.3 to 100.0)	99.7; (98.4 to 100.0)
Anti-HPV 45 cLIA ≥8 mMU/mL	Number Analyzed	534 participants	368 participants
		99.8; (99.0 to 100.0)	99.5; (98.1 to 99.9)
Anti-HPV 52 cLIA ≥8 mMU/mL	Number Analyzed	533 participants	337 participants
		100.0; (99.3 to 100.0)	99.7; (98.4 to 100.0)
Anti-HPV 58 cLIA ≥8 mMU/mL	Number Analyzed	531 participants	332 participants
		100.0; (99.3 to 100.0)	100.0; (98.9 to 100.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 6
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.8 to 1.5
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 11
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.2
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 16
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.2
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 18
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.8 to 1.5
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 31
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.7
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 33
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.6
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 45
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.6 to 1.8
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 52
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.7
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
	Comments	Anti-HPV 58
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.2
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

10. Secondary Outcome

Title	Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Males [Lot 1] Versus 16- to 26-Year-Old Females [Lot 1])
Description	Serum antibody titers for HPV VLPs, Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using cLIA. The serostatus cutoffs (milli Merck U/mL) for HPV types were as follows: HPV Type 6: ≥30, HPV Type 11: ≥16; HPV Type 16: ≥20, HPV Type 18: ≥24, HPV Type 31: ≥10, HPV Type 33: ≥8, HPV Type 45: ≥8, HPV Type 52: ≥8, and HPV Type 58: ≥8.
Time Frame	4 weeks post-vaccination 3 (Month 7)

Outcome Measure Data

Analysis Population Description

9-15-year-old males and 16-26-year-old females who received 3 vaccinations from Lot 1 and met following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range

Arm/Group Title		Base Study: 9- to 15-Year-Old Males (Lot 1)	Base Study: 16- to 26-Year-Old Females (Lot 1)
Arm/Group Description:		9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed		570	378
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Anti-HPV 6 cLIA ≥30 mMU/mL	Number Analyzed	559 participants	328 participants
		99.8; (99.0 to 100.0)	99.7; (98.3 to 100.0)
Anti-HPV 11 cLIA ≥16 mMU/mL	Number Analyzed	559 participants	332 participants
		100.0; (99.3 to 100.0)	100.0; (98.9 to 100.0)
Anti-HPV 16 cLIA ≥20 mMU/mL	Number Analyzed	569 participants	329 participants
		100.0; (99.4 to 100.0)	100.0; (98.9 to 100.0)
Anti-HPV 18 cLIA ≥24 mMU/mL	Number Analyzed	567 participants	345 participants
		100.0; (99.4 to 100.0)	99.7; (98.4 to 100.0)
Anti-HPV 31 cLIA ≥10 mMU/mL	Number Analyzed	564 participants	340 participants
		100.0; (99.3 to 100.0)	99.7; (98.4 to 100.0)
Anti-HPV 33 cLIA ≥8 mMU/mL	Number Analyzed	567 participants	354 participants
		100.0; (99.4 to 100.0)	99.7; (98.4 to 100.0)
Anti-HPV 45 cLIA ≥8 mMU/mL	Number Analyzed	570 participants	368 participants
		100.0; (99.4 to 100.0)	99.5; (98.1 to 99.9)
Anti-HPV 52 cLIA ≥8 mMU/mL	Number Analyzed	568 participants	337 participants
		100.0; (99.4 to 100.0)	99.7; (98.4 to 100.0)
Anti-HPV 58 cLIA ≥8 mMU/mL	Number Analyzed	566 participants	332 participants
		100.0; (99.4 to 100.0)	100.0; (98.9 to 100.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 6
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.5
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 11
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.2
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 16
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.2
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 18
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.6
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 31
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.7
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 33
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.6
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 45
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -0.1 to 2.0
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 52
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.7
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
	Comments	Anti-HPV 58
	Type of Statistical Test	Non-Inferiority
	Comments	Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Miettinen and Nurminen
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.2
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)

11. Secondary Outcome

Title	Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (Lot Consistency Study)
Description	Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post- vaccination 3 using cLIA. The serostatus cutoffs (milli Merck U/mL) for HPV types were as follows: HPV Type 6: ≥30, HPV Type 11: ≥16; HPV Type 16: ≥20, HPV Type 18: ≥24, HPV Type 31: ≥10, HPV Type 33: ≥8, HPV Type 45: ≥8, HPV Type 52: ≥8, and HPV Type 58: ≥8.
Time Frame	4 weeks post-vaccination 3 (Month 7)

Outcome Measure Data

Analysis Population Description

9- to 15-year-old females who received 3 vaccinations from Lots 1, 2, and 3 and met following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range

Arm/Group Title		Base Study: 9- to 15-Year-Old Females (Lot 1)	Base Study: 9- to 15-Year-Old Females (Lot 2)	Base Study: 9- to 15-Year-Old Females (Lot 3)
Arm/Group Description:		9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 2.	9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 3.
Overall Number of Participants Analyzed		535	549	565
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
HPV 6 cLIA ≥30 mMU/mL	Number Analyzed	517 participants	536 participants	544 participants
		99.8; (98.9 to 100.0)	99.8; (99.0 to 100.0)	99.3; (98.1 to 99.8)
HPV 11 cLIA ≥16 mMU/mL	Number Analyzed	517 participants	536 participants	544 participants
		100.0; (99.3 to 100.0)	100.0; (99.3 to 100.0)	99.6; (98.7 to 100.0)
HPV 16 cLIA ≥20 mMU/mL	Number Analyzed	529 participants	542 participants	556 participants
		100.0; (99.3 to 100.0)	100.0; (99.3 to 100.0)	99.6; (98.7 to 100.0)
HPV 18 cLIA ≥24 mMU/mL	Number Analyzed	531 participants	547 participants	563 participants
		99.8; (99.0 to 100.0)	100.0; (99.3 to 100.0)	99.6; (98.7 to 100.0)
HPV 31 cLIA ≥10 mMU/mL	Number Analyzed	522 participants	542 participants	553 participants
		100.0; (99.3 to 100.0)	100.0; (99.3 to 100.0)	99.8; (99.0 to 100.0)
HPV 33 cLIA ≥8 mMU/mL	Number Analyzed	534 participants	543 participants	560 participants
		100.0; (99.3 to 100.0)	100.0; (99.3 to 100.0)	99.6; (98.7 to 100.0)
HPV 45 cLIA ≥8 mMU/mL	Number Analyzed	534 participants	548 participants	565 participants
		99.8; (99.0 to 100.0)	100.0; (99.3 to 100.0)	99.6; (98.7 to 100.0)
HPV 52 cLIA ≥8 mMU/mL	Number Analyzed	533 participants	547 participants	562 participants
		100.0; (99.3 to 100.0)	100.0; (99.3 to 100.0)	99.6; (98.7 to 100.0)
HPV 58 cLIA ≥8 mMU/mL	Number Analyzed	531 participants	539 participants	560 participants
		100.0; (99.3 to 100.0)	100.0; (99.3 to 100.0)	99.6; (98.7 to 100.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 6
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.9 to 0.9
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 6
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.7
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 6
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.7
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 11
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.7
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 11
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.3
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 11
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.3
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 16
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.7
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 16
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.3
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 16
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.3
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 18
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.5
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 18
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.1
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 18
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.3
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 31
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.7
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 31
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.6 to 1.0
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 31
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.5 to 1.0
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 33
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.7
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 33
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.3
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 33
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.3
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 45
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.5
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 45
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.7 to 1.1
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 45
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.3
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 52
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.7
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 52
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.3
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 52
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.3
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
	Comments	Anti-HPV 58
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.7
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 58
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.3
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
	Comments	Anti-HPV 58
	Type of Statistical Test	Equivalence
	Comments	equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation	Estimation Parameter	Percentage Point Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.3
	Estimation Comments	Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)

12. Secondary Outcome

Title	Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Females
Description	Persistent infection is when a participant is positive by polymerase chain reaction (PCR) for the same HPV type in cervicovaginal/external genital swabs or tissue specimens collected at consecutive visits at least 6 months (+/-1 month visit window) apart. Incidence was estimated as cases per 10,000 person-years. Person-years follow-up was from beginning of long-term follow-up or when a study participant reached 16 years of age, whichever came later. Per protocol, the extension study included 9- to 15-year-old females regardless of lot administered.
Time Frame	Up to ~Month 126

Outcome Measure Data

Analysis Population Description

The per-protocol effectiveness population, which included participants who were seronegative (by cLIA) to the relevant HPV type(s) at Day 1 (seronegative to both HPV 6 and 11 for analysis of HPV 6 and 11 HPV11-related endpoints), received all 3 doses of 9vHPV vaccine with the correct dose of the clinical material within 1 year, and had no other protocol violation that could interfere with evaluation of vaccine effectiveness.

Arm/Group Title	Extension Study: 9- to 15-Year-Old Females
Arm/Group Description:	In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).
Overall Number of Participants Analyzed	872
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Cases per 10,000 person-years
	52.4; (33.6 to 78.0)

13. Secondary Outcome

Title	Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Males
Description	Persistent infection is when a participant is positive by PCR for the same HPV type in external genital swabs or tissue specimens collected at consecutive visits at least 6 months (+/-1 month visit window) apart. Incidence was estimated as cases per 10,000 person-years. Person-years follow-up was from beginning of long-term follow-up or when a study participant reached 16 years of age, whichever came later.
Time Frame	Up to ~Month 126

Outcome Measure Data

Analysis Population Description

The per-protocol effectiveness population, which included participants who were seronegative (by cLIA) to the relevant HPV type(s) at Day 1 (seronegative to both HPV 6 and 11 for analysis of HPV 6 and 11-related endpoints), received all 3 doses of 9vHPV vaccine with the correct dose of the clinical material within 1 year, and had no other protocol violation that could interfere with evaluation of vaccine effectiveness.

Arm/Group Title	Extension Study: 9- to 15-Year-Old Males
Arm/Group Description:	In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).
Overall Number of Participants Analyzed	261
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Cases per 10,000 person-years
	54.6; (21.9 to 112.4)

14. Secondary Outcome

Title	Extension Study: Combined Incidence of Cervical Intraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia, Vaginal Intraepithelial Neoplasia, Genital Warts, and Cervical/Vulvar/Vaginal Cancers Related to HPV 6/11/16/18/31/33/45/52/58 in Females
Description	The combined incidence of cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, genital warts, and cervical/vulvar/vaginal cancers, related to HPV 6/11/16/18/31/33/45/52/58 was assessed. This outcome measure was determined by clinical/pathologic criteria and positive PCR assay for HPV type. Incidence was estimated as cases per 10,000 person-years. Person-years follow-up was calculated starting from the beginning of the long-term follow-up study or the date when the study participant reached 16 years of age, whichever came later. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.
Time Frame	Up to ~Month 126

Outcome Measure Data

Analysis Population Description

The per-protocol effectiveness population, which included participants who were seronegative (by cLIA) to the relevant HPV type(s) at Day 1 (seronegative to both HPV 6 and 11 for analysis of HPV 6 and 11-related endpoints), received all 3 doses of 9vHPV vaccine with the correct dose of the clinical material within 1 year, and had no other protocol violation that could interfere with evaluation of vaccine effectiveness.

Arm/Group Title	Extension Study: 9- to 15-Year-Old Females
Arm/Group Description:	In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).
Overall Number of Participants Analyzed	866
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Cases per 10,000 person-years
	2.2; (0.1 to 12.2)

15. Secondary Outcome

Title	Extension Study: Combined Incidence of Penile Intraepithelial Neoplasia, Penile/Perineal/Perianal Cancers and Genital Warts Related to HPV 6/11/16/18/31/33/45/52/58 in Males
Description	The combined incidence of penile intraepithelial neoplasia, penile/perineal/perianal cancers, and genital warts related to HPV6/11/16/18/31/33/45/52/58 was assessed. This outcome measure was determined by clinical/pathologic criteria and positive PCR assay for HPV type. Incidence was estimated as cases per 10,000 person-years. For each study participant, person-years follow up was calculated starting from the beginning of the long-term follow-up study or the date when the study participant reached 16 years of age, whichever came later.
Time Frame	Up to ~Month 126

Outcome Measure Data

Analysis Population Description

The per-protocol effectiveness population, which included participants who were seronegative (by cLIA) to the relevant HPV type(s) at Day 1 (seronegative to both HPV 6 and 11 for analysis of HPV 6 and 11-related endpoints), received all 3 doses of 9vHPV vaccine with the correct dose of the clinical material within 1 year, and had no other protocol violation that could interfere with evaluation of vaccine effectiveness.

Arm/Group Title	Extension Study: 9- to 15-Year-Old Males
Arm/Group Description:	In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).
Overall Number of Participants Analyzed	261
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Cases per 10,000 person-years
	0.0; (0.0 to 28.9)

16. Secondary Outcome

Title	Extension Study: Percentage of Participants With Vaccine-Related or Procedure-Related Serious Adverse Events
Description	A serious adverse event (SAE) included a death which resulted in the participant discontinuing the study, a serious adverse experience that was considered by an investigator who was a qualified physician to be possibly, probably, or definitely vaccine related or study procedure related. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.
Time Frame	Up to ~Month 126

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 study vaccination in the base study and had follow-up data.

Arm/Group Title	Extension Study: 9- to 15-Year-Old Females	Extension Study: 9- to 15-Year-Old Males
Arm/Group Description:	In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).	In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2)
Overall Number of Participants Analyzed	971	301
Measure Type: Number; Unit of Measure: Percentage of Participants
	0.0	0.0

Adverse Events

Time Frame

Base Study: Up to ~12 months; Extension Study: Up to ~126 months

Adverse Event Reporting Description

Base Study and Extension Study: ACM was analyzed in all randomized participants. Safety was analyzed in all participants who received at least one dose of 9vHPV and had available follow-up data, per protocol. ACM and safety were reported separately for base study, first extension (EXT1) and second extension (EXT2).

Arm/Group Title

Base Study: 9- to 15-Year-Old Females (Lot 1)

Base Study: 9- to 15-Year-Old Females (Lot 2)

Base Study: 9- to 15-Year-Old Females (Lot 3)

Base Study: 9- to 15-Year-Old Males (Lot 1)

Base Study: 16- to 26-Year-Old Females (Lot 1)

EXT1: 9- to 15-Year-Old Females

EXT1: 9- to 15-Year-Old Males

EXT2: 9- to 15-Year-Old Females

EXT2: 9- to 15-Year-Old Males

Arm/Group Description

9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.

9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 2.

9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 3.

9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.

9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.

In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension study, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1).

In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension study, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1).

In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension study, the participants were followed up for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).

In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension study, the participants were followed up for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).

All-Cause Mortality

Base Study: 9- to 15-Year-Old Females (Lot 1)

Base Study: 9- to 15-Year-Old Females (Lot 2)

Base Study: 9- to 15-Year-Old Females (Lot 3)

Base Study: 9- to 15-Year-Old Males (Lot 1)

Base Study: 16- to 26-Year-Old Females (Lot 1)

EXT1: 9- to 15-Year-Old Females

EXT1: 9- to 15-Year-Old Males

EXT2: 9- to 15-Year-Old Females

EXT2: 9- to 15-Year-Old Males

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Total

0/648 (0.00%)

0/643 (0.00%)

0/644 (0.00%)

0/669 (0.00%)

0/470 (0.00%)

1/1604 (0.06%)

0/568 (0.00%)

1/971 (0.10%)

0/301 (0.00%)

Serious Adverse Events

Base Study: 9- to 15-Year-Old Females (Lot 1)

Base Study: 9- to 15-Year-Old Females (Lot 2)

Base Study: 9- to 15-Year-Old Females (Lot 3)

Base Study: 9- to 15-Year-Old Males (Lot 1)

Base Study: 16- to 26-Year-Old Females (Lot 1)

EXT1: 9- to 15-Year-Old Females

EXT1: 9- to 15-Year-Old Males

EXT2: 9- to 15-Year-Old Females

EXT2: 9- to 15-Year-Old Males

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Total

6/643 (0.93%)

2/639 (0.31%)

8/641 (1.25%)

11/662 (1.66%)

15/466 (3.22%)

2/1604 (0.12%)

0/568 (0.00%)

3/971 (0.31%)

0/301 (0.00%)

Gastrointestinal disorders

Abdominal pain † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

0/641 (0.00%)

0

0/662 (0.00%)

0

1/466 (0.21%)

3

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Colitis † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

1/641 (0.16%)

1

0/662 (0.00%)

0

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Colitis ulcerative † 1

1/643 (0.16%)

1

0/639 (0.00%)

0

0/641 (0.00%)

0

0/662 (0.00%)

0

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Gastritis † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

1/641 (0.16%)

1

0/662 (0.00%)

0

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

General disorders

Pyrexia † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

1/641 (0.16%)

1

0/662 (0.00%)

0

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Hepatobiliary disorders

Biliary colic † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

0/641 (0.00%)

0

0/662 (0.00%)

0

1/466 (0.21%)

1

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Infections and infestations

Appendicitis † 1

1/643 (0.16%)

1

1/639 (0.16%)

1

0/641 (0.00%)

0

3/662 (0.45%)

3

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Disseminated tuberculosis † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

0/641 (0.00%)

0

0/662 (0.00%)

0

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

1/971 (0.10%)

1

0/301 (0.00%)

0

Gastroenteritis † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

0/641 (0.00%)

0

1/662 (0.15%)

1

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Gastrointestinal infection † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

1/641 (0.16%)

1

0/662 (0.00%)

0

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Infectious mononucleosis † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

1/641 (0.16%)

1

0/662 (0.00%)

0

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Paronychia † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

1/641 (0.16%)

1

0/662 (0.00%)

0

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Pharyngotonsillitis † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

0/641 (0.00%)

0

1/662 (0.15%)

1

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Pneumonia † 1

1/643 (0.16%)

1

0/639 (0.00%)

0

0/641 (0.00%)

0

0/662 (0.00%)

0

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Sepsis † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

0/641 (0.00%)

0

0/662 (0.00%)

0

0/466 (0.00%)

0

1/1604 (0.06%)

1

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Tonsillitis † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

1/641 (0.16%)

1

0/662 (0.00%)

0

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Upper respiratory tract infection † 1

1/643 (0.16%)

1

0/639 (0.00%)

0

0/641 (0.00%)

0

0/662 (0.00%)

0

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Urinary tract infection † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

0/641 (0.00%)

0

0/662 (0.00%)

0

1/466 (0.21%)

1

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Injury, poisoning and procedural complications

Ankle fracture † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

0/641 (0.00%)

0

1/662 (0.15%)

1

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Concussion † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

1/641 (0.16%)

1

0/662 (0.00%)

0

1/466 (0.21%)

1

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Foot fracture † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

0/641 (0.00%)

0

0/662 (0.00%)

0

1/466 (0.21%)

1

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Gun shot wound † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

0/641 (0.00%)

0

0/662 (0.00%)

0

1/466 (0.21%)

1

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Limb injury † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

0/641 (0.00%)

0

1/662 (0.15%)

1

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Tibia fracture † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

0/641 (0.00%)

0

1/662 (0.15%)

1

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Tongue injury † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

1/641 (0.16%)

1

0/662 (0.00%)

0

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)

0

0/301 (0.00%)

0

Nervous system disorders

Brain injury † 1

0/643 (0.00%)

0

0/639 (0.00%)

0

0/641 (0.00%)

0

1/662 (0.15%)

1

0/466 (0.00%)

0

0/1604 (0.00%)

0

0/568 (0.00%)

0

0/971 (0.00%)