Trial Outcomes & Findings for Multivalent HPV (Human Papillomavirus) Vaccine Study in 16- to 26-Year Old Men and Women (V503-003) (NCT NCT01651949)

NCT ID: NCT01651949

Last Updated: 2018-11-27

Results Overview

Serum antibodies to HPV types 6/11/16/18/31/33/45/52/58 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2520 participants

Primary outcome timeframe

Four weeks post vaccination 3 (Month 7)

Results posted on

2018-11-27

Participant Flow

Participant milestones

Participant milestones
Measure	Heterosexual Males Healthy heterosexual males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Females Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Men Who Have Sex With Men (MSM) Healthy MSM 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Overall Study STARTED	1106	1101	313
Overall Study Vaccination 1	1103	1099	313
Overall Study Vaccination 2	1089	1069	298
Overall Study Vaccination 3	1067	1037	291
Overall Study COMPLETED	1053	1015	282
Overall Study NOT COMPLETED	53	86	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Heterosexual Males Healthy heterosexual males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Females Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Men Who Have Sex With Men (MSM) Healthy MSM 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Overall Study Unknown status	4	4	0
Overall Study Lost to Follow-up	30	56	20
Overall Study Protocol Violation	0	2	1
Overall Study Physician Decision	0	2	0
Overall Study Adverse Event	0	2	1
Overall Study Screen failure	2	2	0
Overall Study Withdrawal by Subject	17	18	9

Baseline Characteristics

Multivalent HPV (Human Papillomavirus) Vaccine Study in 16- to 26-Year Old Men and Women (V503-003)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Heterosexual Males n=1106 Participants Healthy heterosexual males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Females n=1101 Participants Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Men Who Have Sex With Men (MSM) n=313 Participants Healthy MSM 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Total n=2520 Participants Total of all reporting groups
Age, Continuous	20.8 Years STANDARD_DEVIATION 3.0 • n=5 Participants	21.3 Years STANDARD_DEVIATION 2.9 • n=7 Participants	22.2 Years STANDARD_DEVIATION 2.4 • n=5 Participants	21.2 Years STANDARD_DEVIATION 2.9 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1101 Participants n=7 Participants	0 Participants n=5 Participants	1101 Participants n=4 Participants
Sex: Female, Male Male	1106 Participants n=5 Participants	0 Participants n=7 Participants	313 Participants n=5 Participants	1419 Participants n=4 Participants

PRIMARY outcome

Timeframe: Four weeks post vaccination 3 (Month 7)

Population: The analysis set includes heterosexual male and female participants who received the 3 vaccinations, were seronegative to the appropriate HPV type at baseline, and had Month 7 immunogenicity results for the appropriate HPV type. Per-protocol non-inferiority analysis compared heterosexual males and females only.

Serum antibodies to HPV types 6/11/16/18/31/33/45/52/58 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL

Outcome measures

Outcome measures
Measure	Heterosexual Males n=914 Participants Healthy heterosexual males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Females n=884 Participants Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Men Who Have Sex With Men n=239 Participants Healthy MSM 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Geometric Mean Titers (GMTs) to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 52 (n=907, 849, 232)	386.8 milli Merck Units/mL Interval 363.4 to 411.6	335.2 milli Merck Units/mL Interval 314.3 to 357.6	233.1 milli Merck Units/mL Interval 206.0 to 263.7
Geometric Mean Titers (GMTs) to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 6 (n=847, 708, 164)	782.0 milli Merck Units/mL Interval 738.0 to 828.7	703.9 milli Merck Units/mL Interval 660.6 to 749.9	568.9 milli Merck Units/mL Interval 498.7 to 649.0
Geometric Mean Titers (GMTs) to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 11 (n=851, 712, 165)	616.7 milli Merck Units/mL Interval 582.4 to 653.0	564.9 milli Merck Units/mL Interval 530.6 to 601.3	437.7 milli Merck Units/mL Interval 384.4 to 498.5
Geometric Mean Titers (GMTs) to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 16 (n=899, 781, 212)	3346.0 milli Merck Units/mL Interval 3158.9 to 3544.1	2788.3 milli Merck Units/mL Interval 2621.4 to 2965.8	2294.0 milli Merck Units/mL Interval 2037.8 to 2582.5
Geometric Mean Titers (GMTs) to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 18 (n=906, 831, 220)	808.2 milli Merck Units/mL Interval 754.9 to 865.4	679.8 milli Merck Units/mL Interval 633.1 to 730.1	608.1 milli Merck Units/mL Interval 529.4 to 698.5
Geometric Mean Titers (GMTs) to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 31 (n=908, 826, 227)	708.5 milli Merck Units/mL Interval 662.7 to 757.6	570.1 milli Merck Units/mL Interval 531.5 to 611.5	420.7 milli Merck Units/mL Interval 368.0 to 480.9
Geometric Mean Titers (GMTs) to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 33 (n=901, 853, 230)	384.8 milli Merck Units/mL Interval 362.5 to 408.4	322.0 milli Merck Units/mL Interval 302.9 to 342.3	252.3 milli Merck Units/mL Interval 224.2 to 283.8
Geometric Mean Titers (GMTs) to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 45 (n=909, 871, 232)	235.6 milli Merck Units/mL Interval 219.0 to 253.6	185.7 milli Merck Units/mL Interval 172.3 to 200.2	157.5 milli Merck Units/mL Interval 136.2 to 182.2
Geometric Mean Titers (GMTs) to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 58 (n=897, 839, 223)	509.8 milli Merck Units/mL Interval 479.9 to 541.6	409.3 milli Merck Units/mL Interval 384.5 to 435.7	319.8 milli Merck Units/mL Interval 283.2 to 361.0

PRIMARY outcome

Timeframe: Up to 5 days after any vaccination

Population: The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.

An adverse experience (AE) is 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 product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Injection-site AEs prompted on the Vaccination Report Card (VRC) were erythema, pain, and swelling. Participants were instructed to use the Vaccination Report Card to record AEs daily after each study vaccination.

Outcome measures

Outcome measures
Measure	Heterosexual Males n=1394 Participants Healthy heterosexual males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Females n=1075 Participants Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Men Who Have Sex With Men Healthy MSM 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Percentage of Participants With One or More Injection-site Adverse Experiences Prompted on the Vaccination Report Card Overall injection-site AEs	66.7 Percentage of Participants	84.0 Percentage of Participants	—
Percentage of Participants With One or More Injection-site Adverse Experiences Prompted on the Vaccination Report Card Injection-site Erythema	20.7 Percentage of Participants	32.2 Percentage of Participants	—
Percentage of Participants With One or More Injection-site Adverse Experiences Prompted on the Vaccination Report Card Injection-site Pain	63.4 Percentage of Participants	82.5 Percentage of Participants	—
Percentage of Participants With One or More Injection-site Adverse Experiences Prompted on the Vaccination Report Card Injection-site Swelling	20.2 Percentage of Participants	37.5 Percentage of Participants	—

PRIMARY outcome

Timeframe: Up to 5 days after any vaccination

Population: The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.

Participants were instructed by the investigator to use the Vaccination Report Card to document evening oral temperature daily after each study vaccination

Outcome measures

Outcome measures
Measure	Heterosexual Males n=1386 Participants Healthy heterosexual males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Females n=1066 Participants Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Men Who Have Sex With Men Healthy MSM 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Percentage of Participants With Elevated Oral Body Temperature (>=37.8° C, >=100° F)	4.4 Percentage of Participants	5.9 Percentage of Participants	—

PRIMARY outcome

Timeframe: Up to Month 12

Population: The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.

An AE is 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 product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE.

Outcome measures

Outcome measures
Measure	Heterosexual Males n=1394 Participants Healthy heterosexual males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Females n=1075 Participants Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Men Who Have Sex With Men Healthy MSM 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Percentage of Participants With an Adverse Event	76.2 Percentage of Participants	89.4 Percentage of Participants	—

PRIMARY outcome

Timeframe: Up to Month 12

Population: The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.

Outcome measures

Outcome measures
Measure	Heterosexual Males n=1394 Participants Healthy heterosexual males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Females n=1075 Participants Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Men Who Have Sex With Men Healthy MSM 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Percentage of Participants Who Had Study Vaccine Discontinued Due to an Adverse Event	0.1 Percentage of Participants	0.3 Percentage of Participants	—

SECONDARY outcome

Timeframe: Four weeks post vaccination 3 (Month 7)

Population: The analysis set includes participants who received the 3 vaccinations, were seronegative to the appropriate HPV type at baseline, and had Month 7 immunogenicity results for the appropriate HPV type. Per-protocol non-inferiority analysis compared heterosexual males and females only.

Serum antibodies to HPV types were measured with a Competitive Luminex Immunoassay. 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 Types 33, 45, 52, and 58: ≥8.

Outcome measures

Outcome measures
Measure	Heterosexual Males n=914 Participants Healthy heterosexual males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Females n=884 Participants Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Men Who Have Sex With Men n=239 Participants Healthy MSM 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Percentage of Participants With Seroconversion to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 16 (n=899, 781, 212)	100 Percentage of Participants Interval 99.6 to 100.0	99.9 Percentage of Participants Interval 99.3 to 100.0	100 Percentage of Participants Interval 98.3 to 100.0
Percentage of Participants With Seroconversion to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 6 (n=847, 708, 164)	99.6 Percentage of Participants Interval 99.0 to 99.9	99.6 Percentage of Participants Interval 98.8 to 99.9	99.4 Percentage of Participants Interval 96.6 to 100.0
Percentage of Participants With Seroconversion to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 11 (n=851, 712, 165)	100 Percentage of Participants Interval 99.6 to 100.0	99.9 Percentage of Participants Interval 99.2 to 100.0	100 Percentage of Participants Interval 97.8 to 100.0
Percentage of Participants With Seroconversion to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 18 (n=906, 831, 220)	99.9 Percentage of Participants Interval 99.4 to 100.0	99.8 Percentage of Participants Interval 99.1 to 100.0	99.5 Percentage of Participants Interval 97.5 to 100.0
Percentage of Participants With Seroconversion to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 31 (n=908, 826, 227)	100 Percentage of Participants Interval 99.6 to 100.0	100 Percentage of Participants Interval 99.6 to 100.0	100 Percentage of Participants Interval 98.4 to 100.0
Percentage of Participants With Seroconversion to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 33 (n=901, 853, 230)	100 Percentage of Participants Interval 99.6 to 100.0	99.9 Percentage of Participants Interval 99.3 to 100.0	100 Percentage of Participants Interval 98.4 to 100.0
Percentage of Participants With Seroconversion to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 45 (n=909, 871, 232)	99.8 Percentage of Participants Interval 99.2 to 100.0	99.5 Percentage of Participants Interval 98.8 to 99.9	100 Percentage of Participants Interval 98.4 to 100.0
Percentage of Participants With Seroconversion to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 52 (n=907, 849, 232)	100 Percentage of Participants Interval 99.6 to 100.0	99.8 Percentage of Participants Interval 99.2 to 100.0	100 Percentage of Participants Interval 98.4 to 100.0
Percentage of Participants With Seroconversion to the HPV Types Contained in the 9vHPV Vaccine Anti-HPV Type 58 (n=897, 839, 223)	100 Percentage of Participants Interval 99.6 to 100.0	99.8 Percentage of Participants Interval 99.1 to 100.0	100 Percentage of Participants Interval 98.4 to 100.0

Adverse Events

Heterosexual and MSM Males

Serious events: 23 serious events

Other events: 976 other events

Deaths: 0 deaths

Females

Serious events: 26 serious events

Other events: 924 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Heterosexual and MSM Males n=1394 participants at risk Healthy heterosexual and MSM males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Females n=1075 participants at risk Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
General disorders Injection site erythema	20.9% 291/1394 • Number of events 422 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	32.4% 348/1075 • Number of events 539 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
General disorders Injection site pain	63.6% 886/1394 • Number of events 1877 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	83.1% 893/1075 • Number of events 2101 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
General disorders Injection site swelling	20.4% 285/1394 • Number of events 431 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	38.0% 408/1075 • Number of events 661 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Nervous system disorders Headache	14.3% 200/1394 • Number of events 271 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	22.9% 246/1075 • Number of events 378 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	Heterosexual and MSM Males n=1394 participants at risk Healthy heterosexual and MSM males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6	Females n=1075 participants at risk Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Cardiac disorders Atrioventricular block second degree	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Congenital, familial and genetic disorders Familial periodic paralysis	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Gastrointestinal disorders Constipation	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.19% 2/1075 • Number of events 2 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Gastrointestinal disorders Vomiting	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
General disorders Cyst rupture	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
General disorders Device dislocation	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Hepatobiliary disorders Cholecystitis	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Infections and infestations Anal abscess	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Infections and infestations Appendicitis	0.14% 2/1394 • Number of events 2 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Infections and infestations Appendicitis perforated	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Infections and infestations Dengue fever	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Infections and infestations Escherichia urinary tract infection	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Infections and infestations External ear cellulitis	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Infections and infestations Infectious mononucleosis	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Infections and infestations Pilonidal cyst	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Infections and infestations Postoperative wound infection	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Infections and infestations Pulmonary tuberculosis	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Infections and infestations Viral infection	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Injury, poisoning and procedural complications Concussion	0.14% 2/1394 • Number of events 2 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Injury, poisoning and procedural complications Exposure to communicable disease	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Injury, poisoning and procedural complications Radius fracture	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Injury, poisoning and procedural complications Tibia fracture	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Musculoskeletal and connective tissue disorders Ligament disorder	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Nervous system disorders Cerebrovascular accident	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Nervous system disorders Migraine	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Nervous system disorders Syncope	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Pregnancy, puerperium and perinatal conditions Abortion incomplete	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.37% 4/1075 • Number of events 4 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.19% 2/1075 • Number of events 2 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Pregnancy, puerperium and perinatal conditions Foetal malpresentation	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Psychiatric disorders Anxiety	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Psychiatric disorders Psychotic disorder	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Psychiatric disorders Schizophreniform disorder	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Renal and urinary disorders Nephrolithiasis	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Renal and urinary disorders Renal failure acute	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Reproductive system and breast disorders Ovarian cyst ruptured	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.09% 1/1075 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Skin and subcutaneous tissue disorders Subcutaneous emphysema	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Surgical and medical procedures Abortion induced	0.00% 0/1394 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.37% 4/1075 • Number of events 4 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Vascular disorders Haematoma	0.07% 1/1394 • Number of events 1 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.	0.00% 0/1075 • Up to Month 12 The analysis set includes all participants who received \>=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.