Download PDF

Clinical Trial Results:
A Phase 3, randomized, placebo-controlled clinical study to evaluate the efficacy, immunogenicity and safety of the 9vHPV vaccine in Japanese males, 16 to 26 years of age.

Summary
EudraCT number	2020-001047-67
Trial protocol	Outside EU/EEA
Global end of trial date	23 Jul 2025

Results information
Results version number	v1(current)
This version publication date	22 Jan 2026
First version publication date	22 Jan 2026
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

V503-064

ISRCTN number

US NCT number

NCT04635423

WHO universal trial number (UTN)

Other trial identifiers

jRCT: jRCT2031200217

Sponsor organisation name

Merck Sharp & Dohme LLC

Sponsor organisation address

126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

23 Jul 2025

Is this the analysis of the primary completion data?

Yes

Primary completion date

31 Dec 2023

Global end of trial reached?

Yes

Global end of trial date

23 Jul 2025

Was the trial ended prematurely?

Main objective of the trial

The purposes of this study are to evaluate the efficacy of V503 (9-valent human papillomavirus [9vHPV] vaccine) in preventing human papillomavirus (HPV)-related anogenital persistent infection, and to evaluate the safety/tolerability of V503, in Japanese males who are 16 to 26 years of age. It is hypothesized that administration of a 3-dose regimen of V503 reduces the combined incidence of HPV 6/11/16/18-related anogenital persistent infection, as well as the combined incidence of HPV31/33/45/52/58-related anogenital persistent infection, compared with placebo. The study includes a Base Study to assess efficacy and safety of V503, and an Extension Study. Participants in the placebo arm of the Base Study will be eligible to receive V503 on Day 1, Month 2, and Month 6 of the Extension Study. Participants in the V503 arm of the Base Study who received less than 3 doses of V503 in the Base Study will be offered the opportunity to complete the 3-dose regimen in the Extension Study.

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

Background therapy

Evidence for comparator

Actual start date of recruitment

30 Nov 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Japan: 1059

Worldwide total number of subjects

1059

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1052

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Participants were equally randomized to V503 and placebo in the base study to evaluate efficacy, immunogenicity, and safety outcome measures. After the end of the base study, eligible participants could be enrolled in the optional open label study extension.

Screening details

A total of 1059 participants who met the eligibility criteria were randomized in the base study.

Period 1 title

Base Study

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Are arms mutually exclusive

Yes

V503

Arm description

In the base study, participants received an intramuscular (IM) injection of V503 at Day 1, Month 2, and Month 6.

Arm type

Experimental

Investigational medicinal product name

V503

Investigational medicinal product code

Other name

9vHPV vaccine, SILGARD®9, GARDASIL™9

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

9-valent vaccine, HPV6/11/16/18/31/33/45/52/58, L1 virus-like particle (VLP) 30/40/60/40/20/20/20/20/20mcg per dose.

Placebo

Arm description

In the base study, participants received an IM injection of placebo at Day 1, Month 2, and Month 6.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.9% sodium chloride (NaCL)

Number of subjects in period 1	V503	Placebo
Started	529	530
Vaccination 1: Day 1	529	530
Vaccination 2: Month 2	523	518
Vaccination 3: Month 6	514	508
Completed	464	472
Not completed	65	58
Consent withdrawn by subject	57	42
Lost to follow-up	8	16

Period 2 title

Extension Study

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

V503 → Open Label V503 Extension Study

Arm description

Participants from the V503 arm of the base study who did not complete the 3-dose series received 1 or 2 doses of V503, on Day 1, or Day 1 and Month 4 of the open label extension study.

Arm type

Experimental

Investigational medicinal product name

V503

Investigational medicinal product code

Other name

9vHPV vaccine, SILGARD®9, GARDASIL™9

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

9-valent vaccine, HPV6/11/16/18/31/33/45/52/58, L1 virus-like particle (VLP) 30/40/60/40/20/20/20/20/20mcg per dose.

Placebo → Open Label V503 Extension Study

Arm description

Participants from the placebo arm of the base study who did not complete the 3-dose series received 3 doses of V503 on Day 1, Month 2 and Month 6 of the open label extension study.

Arm type

Experimental

Investigational medicinal product name

V503

Investigational medicinal product code

Other name

9vHPV vaccine, SILGARD®9, GARDASIL™9

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

9-valent vaccine, HPV6/11/16/18/31/33/45/52/58, L1 virus-like particle (VLP) 30/40/60/40/20/20/20/20/20mcg per dose.

Number of subjects in period 2 ^[1]	V503 → Open Label V503 Extension Study	Placebo → Open Label V503 Extension Study
Started	2	381
Completed	2	367
Not completed	0	14
Physician decision	-	1
Consent withdrawn by subject	-	10
Lost to follow-up	-	3

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all base study participants were enrolled in the extension study because participation in the extension study was optional and participants had to meet certain eligibility criteria.

Baseline characteristics

Top of page

Reporting group title

V503

Reporting group description

In the base study, participants received an intramuscular (IM) injection of V503 at Day 1, Month 2, and Month 6.

Reporting group title

Placebo

Reporting group description

In the base study, participants received an IM injection of placebo at Day 1, Month 2, and Month 6.

Reporting group values	V503	Placebo	Total
Number of subjects	529	530	1059
Age categorical
Units: Subjects
Age Continuous
Units: Years
arithmetic mean (standard deviation)	22.9 ( 2.1 )	22.8 ( 2.1 )	-
Sex: Female, Male
Units: Participants
Female	0	0	0
Male	529	530	1059
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0
Asian	529	530	1059
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	0	0
White	0	0	0
More than one race	0	0	0
Unknown or Not Reported	0	0	0
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	0	0
Not Hispanic or Latino	529	530	1059
Unknown or Not Reported	0	0	0
Sexual Orientation Participant Subgroups
Participant randomization was stratified by sexual orientation heterosexual males (HM) or males who have sex with males (MSM). For HM, participants must be a heterosexual male, who has had exclusively female sexual partners, and has 1 to 5 lifetime female sexual partners at the time of enrollment. For MSM, participants must identify themselves as a male who has sex with males, must have engaged in either anal intercourse or oral sex with another male sexual partner within the last year, and have 0 to 5 lifetime male and/or female sexual partners at the time of enrollment.
Units: Subjects
Heterosexual Males (HM)	473	474	947
Males Who Have Sex With Males (MSM)	56	56	112

End points

Top of page

Reporting group title

V503

Reporting group description

In the base study, participants received an intramuscular (IM) injection of V503 at Day 1, Month 2, and Month 6.

Reporting group title

Placebo

Reporting group description

In the base study, participants received an IM injection of placebo at Day 1, Month 2, and Month 6.

Reporting group title

V503 → Open Label V503 Extension Study

Reporting group description

Participants from the V503 arm of the base study who did not complete the 3-dose series received 1 or 2 doses of V503, on Day 1, or Day 1 and Month 4 of the open label extension study.

Reporting group title

Placebo → Open Label V503 Extension Study

Reporting group description

Participants from the placebo arm of the base study who did not complete the 3-dose series received 3 doses of V503 on Day 1, Month 2 and Month 6 of the open label extension study.

Primary: Percentage of participants with ≥1 systemic AE

Top of page

End point title

Percentage of participants with ≥1 systemic AE

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced at least 1 systemic AE is reported here for all randomized participants in the All Participants as Treated (APaT) population. Analysis population included all randomized participants in base study who received at least 1 dose of the V503 vaccine or placebo and have provided safety data at any time during the study.

End point type

Primary

End point timeframe

Up to 15 days after any vaccination

End point values	V503	Placebo
Number of subjects analysed	529	530
Units: Percentage of Participants
number (not applicable)	20.2	19.8

Difference in Percentage

Comparison groups

V503 v Placebo

Number of subjects included in analysis

1059

Analysis specification

Pre-specified

Analysis type

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentage

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.4

upper limit

5.2

Primary: Combined incidence of HPV 6/11/16/18-related anogenital persistent infection

Top of page

End point title

Combined incidence of HPV 6/11/16/18-related anogenital persistent infection

End point description

HPV6/11/16/18-related anogenital persistent infection was defined as polymerase chain reaction (PCR) positivity to at least 1 relevant HPV type in anogenital or biopsy samples from at least 2 consecutive visits 6 months (±1 month visit) or longer apart, or pathology diagnosis of condyloma or penile/perineal/perianal lesions together with PCR detection of at least 1 HPV type in an adjacent section and PCR detection for same HPV type in anogenital sample or biopsy at a separate adjacent visit. Incidence was measured as number of cases/100 person-years. Primary analysis was conducted in the per protocol efficacy (PPE) population including participants who received 3 doses of V503 or placebo in 1 year, had Month 7 swab samples collected postdose 3 with PCR result, were seronegative to relevant HPV type(s) at Day 1 and PCR-negative to relevant HPV type(s) on all samples collected from Day 1 to Month 7, and had no protocol deviations that could interfere with evaluation of vaccine efficacy.

End point type

Primary

End point timeframe

Up to approximately 36 Months

End point values	V503	Placebo
Number of subjects analysed	496	483
Units: Cases per 100 Person-years
number (not applicable)	0.2	2.2

Observed Efficacy

Comparison groups

V503 v Placebo

Number of subjects included in analysis

979

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001 ^[1]

Method

Exact Binomial Method Chan and Bohidar

Parameter type

Observed Efficacy (%)

Point estimate

89.3

Confidence interval

level

95%

sides

2-sided

lower limit

55.4

upper limit

98.2

Notes
[1] - one-sided p-value based on exact binomial method proposed by Chan and Bohidar

Primary: Percentage of participants with solicited injection-site adverse events (AEs)

Top of page

End point title

Percentage of participants with solicited injection-site adverse events (AEs)

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The participant recorded the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 5 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (redness/erythema, tenderness/pain, and swelling) is reported here for all randomized participants in the All Participants as Treated (APaT) population. Analysis population included all randomized participants in base study who received at least 1 dose of the V503 vaccine or placebo and have provided safety data at any time during the study.

End point type

Primary

End point timeframe

Up to 5 days after any vaccination

End point values	V503	Placebo
Number of subjects analysed	529	530
Units: Percentage of Participants
number (not applicable)	69.8	29.6

Difference in Percentages

Comparison groups

V503 v Placebo

Number of subjects included in analysis

1059

Analysis specification

Pre-specified

Analysis type

Method

Miettinen & Nurminen method

Parameter type

Difference in Percentages

Point estimate

40.1

Confidence interval

level

95%

sides

2-sided

lower limit

34.5

upper limit

45.5

Primary: Number of Participants with Elevated Oral Body Temperature

Top of page

End point title

Number of Participants with Elevated Oral Body Temperature ^[2]

End point 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 using the VRC. Per protocol, fever was defined as an oral temperature of ≥99.5°F(37.5°C). The number of participants who had at least 1 oral body temperature reading that was, <99.5°F (<37.5ºC), ≥99.5°F (≥37.5ºC) and <100.4°F (38.0°C), or ≥100.4°F (38.0°C) and <101.3°F(38.5°C), or ≥101.3°F(38.5°C) is reported here for all randomized participants in the APaT population with temperature data available. Analysis population included all randomized participants in base study who received at least 1 dose of the V503 vaccine or placebo and have provided safety data at any time during the study.

End point type

Primary

End point timeframe

Up to 5 days after any vaccination

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between arm comparison were planned for the study.

End point values	V503	Placebo
Number of subjects analysed	527	526
Units: Participants
<99.5°F (37.5°C)	502	496
≥99.5°F (≥37.5ºC) and <100.4°F (38.0°C)	19	22
≥100.4°F (38.0°C) and <101.3°F(38.5°C)	1	1
≥101.3°F(38.5°C)	5	7

No statistical analyses for this end point

Primary: Percentage of participants with ≥1 SAEs

Top of page

End point title

Percentage of participants with ≥1 SAEs ^[3]

End point description

An SAE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention, that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, results in persistent/significant disability/incapacity, is a congenital birth defect, or is another important medical event. The percentage of participants who experienced at least 1 SAE is reported here for all randomized participants in the All Participants as Treated (APaT) population. Analysis population included all randomized participants in the base study who received at least 1 dose of the V503 vaccine or placebo and have provided safety data at any time during the study.

End point type

Primary

End point timeframe

Up to approximately 37 months

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between arm comparison were planned for the study.

End point values	V503	Placebo
Number of subjects analysed	529	530
Units: Percentage of Participants
number (not applicable)	1.3	0.9

No statistical analyses for this end point

Secondary: Combined incidence of HPV 31/33/45/52/58-related anogenital persistent infection

Top of page

End point title

Combined incidence of HPV 31/33/45/52/58-related anogenital persistent infection

End point description

HPV31/33/45/52/58-related anogenital persistent infection was defined as polymerase chain reaction (PCR) positivity to at least 1 relevant HPV type in anogenital or biopsy samples from at least 2 consecutive visits 6 months (±1 month visit) or longer apart, or pathology diagnosis of condyloma or penile/perineal/perianal lesions together with PCR detection of at least 1 HPV type in an adjacent section and PCR detection for same HPV type in anogenital sample or biopsy at a separate adjacent visit. Incidence was measured as number of cases/100 person-years. Primary analysis was conducted in the PPE population.

End point type

Secondary

End point timeframe

Up to approximately 36 Months

End point values	V503	Placebo
Number of subjects analysed	505	493
Units: cases per 100 Person-years
number (not applicable)	0.7	1.9

Observed Efficacy

Comparison groups

V503 v Placebo

Number of subjects included in analysis

998

Analysis specification

Pre-specified

Analysis type

P-value

= 0.023 ^[4]

Method

Exact Binomial Method Chan and Bohidar

Parameter type

Observed Efficacy (%)

Point estimate

63.5

Confidence interval

level

95%

sides

2-sided

lower limit

2.7

upper limit

Notes
[4] - one-sided p-value based on exact binomial method proposed by Chan and Bohidar

Secondary: Geometric mean titers (GMTs) to HPV 6/11/16/18/31/33/45/52/58

Top of page

End point title

Geometric mean titers (GMTs) to HPV 6/11/16/18/31/33/45/52/58

End point description

Antibodies to the HPV types 6/11/16/18/31/33/45/52/58 contained in V503 were measured using a competitive Luminex immunoassay (cLIA). Per protocol, antibody titers were expressed as milli Merck units/milliliter (mMU/mL). GMTs are reported for all participants of the per-protocol immunogenicity population (PPI) which included participants who satisfied all the criteria for the PPE population, and additionally all vaccinations within acceptable day ranges and provided blood samples for serology testing within the acceptable day range. A value of 8888/9999 indicates results were lower than the lower limit of quantitation of the assay.

End point type

Secondary

End point timeframe

Month 7

End point values	V503	Placebo
Number of subjects analysed	456	458
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6	927.3 (850.2 to 1011.3)	21.1 (-9999 to 22.5)
Anti-HPV 11	716.5 (654.4 to 784.5)	8888 (-9999 to 9999)
Anti-HPV 16	3491.6 (3196.5 to 3814.0)	8888 (-9999 to 9999)
Anti-HPV 18	998.0 (904.3 to 1101.4)	45.5 (43.4 to 47.7)
HPV-31	832.1 (753.3 to 919.2)	15.4 (14.3 to 16.5)
HPV-33	489.8 (448.6 to 534.7)	12.7 (11.9 to 13.4)
Anti-HPV 45	326.6 (293.7 to 363.2)	8.5 (-9999 to 9.0)
Anti-HPV 52	390.5 (356.3 to 428.0)	10.1 (9.5 to 10.8)
Anti-HPV 58	588.3 (537.7 to 643.6)	8888 (-9999 to 9999)

No statistical analyses for this end point

Secondary: GMTs to HPV 6/11/16/18/31/33/45/52/58 - Heterosexual Males (HM) Participant Subgroup

Top of page

End point title

GMTs to HPV 6/11/16/18/31/33/45/52/58 - Heterosexual Males (HM) Participant Subgroup

End point description

Antibodies to the HPV types 6/11/16/18/31/33/45/52/58 contained in V503 were measured using a cLIA. Per protocol, antibody titers were expressed as mMU/mL. GMTs are reported for the HM subgroup of the PPI population. A value of 8888/9999 indicates that results were lower than the lower limit of quantitation of the assay.

End point type

Secondary

End point timeframe

Month 7

End point values	V503	Placebo
Number of subjects analysed	408	415
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6	950.2 (866.8 to 1041.6)	21.0 (-9999 to 22.6)
Anti-HPV 11	730.6 (664.4 to 803.4)	8888 (-9999 to 9999)
Anti-HPV 16	3608.3 (3288.6 to 3959.0)	8888 (-9999 to 9999)
Anti-HPV 18	1044.7 (942.7 to 1157.7)	45.1 (42.9 to 47.3)
Anti-HPV 31	867.8 (780.7 to 964.7)	15.1 (14.0 to 16.3)
Anti-HPV 33	495.4 (451.9 to 543.1)	12.6 (11.8 to 13.4)
Anti-HPV 45	333.8 (298.4 to 373.5)	8.4 (-9999 to 9.0)
Ant-HPV 52	408.7 (372.1 to 448.9)	10.0 (9.3 to 10.7)
Anti-HPV 58	609.1 (554.2 to 669.4)	8888 (-9999 to 9999)

No statistical analyses for this end point

Secondary: GMTs to HPV 6/11/16/18/31/33/45/52/58 - Males Who Have Sex with Males (MSM) Participant Subgroup

Top of page

End point title

GMTs to HPV 6/11/16/18/31/33/45/52/58 - Males Who Have Sex with Males (MSM) Participant Subgroup

End point description

Antibodies to the HPV types 6/11/16/18/31/33/45/52/58 contained in V503 were measured using a cLIA. Per protocol, antibody titers were expressed as mMU/mL. GMTs are reported for the MSM subgroup of the PPI population. A value of 8888/9999 indicates that results were lower than the lower limit of quantitation of the assay.

End point type

Secondary

End point timeframe

Month 7

End point values	V503	Placebo
Number of subjects analysed	48	46
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6	740.2 (569.2 to 962.6)	21.5 (-9999 to 27.5)
Anti-HPV 11	598.8 (438.7 to 817.3)	8888 (-9999 to 9999)
Anti-HPV 16	2599.5 (1957.4 to 3452.4)	8888 (-9999 to 9999)
Anti-HPV 18	677.4 (487.6 to 941.0)	49.7 (42.1 to 58.6)
Anti-HPV 31	593.2 (446.0 to 789.0)	17.7 (14.1 to 22.2)
Anti-HPV 33	443.6 (327.9 to 600.1)	13.5 (11.5 to 16.0)
Anti-HPV 45	266.6 (190.1 to 373.8)	9.1 (-9999 to 11.1)
Anti-HPV 52	262.9 (186.7 to 370.2)	11.3 (9.0 to 14.2)
Anti-HPV 58	437.7 (327.8 to 584.5)	-9999 (-9999 to 8.4)

No statistical analyses for this end point

Secondary: Percentage of Participants with Seroconversion to HPV 6/11/16/18/31/33/45/52/58

Top of page

End point title

Percentage of Participants with Seroconversion to HPV 6/11/16/18/31/33/45/52/58

End point description

Percentage of seroconversion to each of HPV 6/11/16/18/31/33/45/52/58 at Month 7 per cLIA from participant serum samples. Seroconversion is defined as a change in participant’s serostatus from seronegative at Day 1 to seropositive at 1 month post last dose Month 7. Participant with anti-HPV cLIA titer at/above serostatus cutoff cLIA values for a given HPV type is seropositive for that type. HPV serostatus cutoffs were Type6: ≥65, Type11: ≥37; Type16: ≥79, Type18: ≥85, Type31: ≥46, Type33: ≥26, Type45: ≥21, Type 52: ≥30, & Type58: ≥31. Percentage of participants with seroconversion is reported in all participants in the PPI population.

End point type

Secondary

End point timeframe

Month 7

End point values	V503	Placebo
Number of subjects analysed	456	458
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 cLIA ≥65 mMU/mL	99.7 (98.6 to 100.0)	3.5 (1.9 to 6.0)
Anti-HPV 11 cLIA ≥37 mMU/mL	99.7 (98.6 to 100.0)	4.1 (2.3 to 6.7)
Anti-HPV 16 cLIA ≥79 mMU/mL	99.6 (98.4 to 99.9)	4.3 (2.6 to 6.6)
Anti-HPV 18 cLIA ≥85 mMU/mL	99.3 (97.9 to 99.9)	8.3 (5.8 to 11.4)
Anti-HPV 31 cLIA ≥46 mMU/mL	98.9 (97.3 to 99.6)	5.6 (3.6 to 8.2)
Anti-HPV 33 cLIA ≥26 mMU/mL	99.8 (98.8 to 100.0)	11.1 (8.3 to 14.4)
Anti-HPV 45 cLIA ≥21 mMU/mL	98.9 (97.4 to 99.6)	9.0 (6.5 to 12.1)
Anti-HPV 52 cLIA ≥30 mMU/mL	98.9 (97.4 to 99.6)	4.2 (2.5 to 6.5)
Anti-HPV 58 cLIA ≥31 mMU/mL	99.3 (98.1 to 99.9)	1.5 (0.6 to 3.1)

No statistical analyses for this end point

Secondary: Percentage of Participants with Seroconversion to HPV 6/11/16/18/31/33/45/52/58 - HM Participant Subgroup

Top of page

End point title

Percentage of Participants with Seroconversion to HPV 6/11/16/18/31/33/45/52/58 - HM Participant Subgroup

End point description

Percentage of seroconversion to each of HPV 6/11/16/18/31/33/45/52/58 at Month 7 per cLIA from participant serum samples. Seroconversion is defined as a change in participant’s serostatus from seronegative at Day 1 to seropositive at 1 month post last dose Month 7. Participant with anti-HPV cLIA titer at/above serostatus cutoff cLIA values for a given HPV type is seropositive for that HPV type. The HPV serostatus cutoffs were Type 6: ≥65, Type 11: ≥37; Type 16: ≥79, Type 18: ≥85, Type 31: ≥46, Type 33: ≥26, Type 45: ≥21, Type 52: ≥30, and Type 58: ≥31. Percentage of participants with seroconversion is reported in the HM subgroup of the PPI population.

End point type

Secondary

End point timeframe

Month 7

End point values	V503	Placebo
Number of subjects analysed	408	415
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 cLIA ≥65 mMU/mL	99.7 (98.5 to 100.0)	3.5 (1.8 to 6.1)
Anti-HPV 11 cLIA ≥37 mMU/mL	99.7 (98.5 to 100.0)	4.4 (2.5 to 7.2)
Anti-HPV 16 cLIA ≥79 mMU/mL	99.5 (98.2 to 99.9)	3.7 (2.1 to 6.0)
Anti-HPV 18 cLIA ≥85 mMU/mL	99.5 (98.1 to 99.9)	7.6 (5.1 to 10.8)
Anti-HPV 31 cLIA ≥46 mMU/mL	99.0 (97.4 to 99.7)	5.2 (3.2 to 7.9)
Anti-HPV 33 cLIA ≥26 mMU/mL	99.8 (98.6 to 100.0)	11.4 (8.4 to 14.9)
Anti-HPV 45 cLIA ≥21 mMU/mL	98.7 (97.1 to 99.6)	8.5 (5.9 to 11.7)
Anti-HPV 52 cLIA ≥30 mMU/mL	99.2 (97.8 to 99.8)	3.8 (2.2 to 6.3)
Anti-HPV 58 cLIA ≥31 mMU/mL	99.3 (97.9 to 99.8)	1.7 (0.7 to 3.4)

No statistical analyses for this end point

Secondary: Percentage of Participants with Seroconversion to HPV 6/11/16/18/31/33/45/52/58 - MSM Participant Subgroup

Top of page

End point title

Percentage of Participants with Seroconversion to HPV 6/11/16/18/31/33/45/52/58 - MSM Participant Subgroup

End point description

Percentage of seroconversion to each of HPV 6/11/16/18/31/33/45/52/58 at Month 7 per cLIA from participant serum samples. Seroconversion is defined as a change in a participant’s serostatus from seronegative at Day 1 to seropositive at 1 month post last dose Month 7. Participant with anti-HPV cLIA titer at/above the serostatus cutoff cLIA values for a given HPV type is seropositive for that HPV type. The HPV serostatus cutoffs were Type 6: ≥65, Type 11: ≥37; Type 16: ≥79, Type 18: ≥85, Type 31: ≥46, Type 33: ≥26, Type 45: ≥21, Type 52: ≥30, and Type 58: ≥31. Percentage of participants with seroconversion is reported in the MSM subgroup of the PPI population.

End point type

Secondary

End point timeframe

Month 7

End point values	V503	Placebo
Number of subjects analysed	48	46
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 cLIA ≥65 mMU/mL	100.0 (91.0 to 100.0)	3.6 (0.1 to 18.3)
Anti-HPV 11 cLIA ≥37 mMU/mL	100.0 (91.0 to 100.0)	0.0 (0.0 to 12.3)
Anti-HPV 16 cLIA ≥79 mMU/mL	100.0 (92.1 to 100.0)	9.5 (2.7 to 22.6)
Anti-HPV 18 cLIA ≥85 mMU/mL	97.7 (88.0 to 99.9)	14.3 (5.4 to 28.5)
Anti-HPV 31 cLIA ≥46 mMU/mL	97.9 (88.9 to 99.9)	8.9 (2.5 to 21.2)
Anti-HPV 33 cLIA ≥26 mMU/mL	100.0 (92.5 to 100.0)	8.7 (2.4 to 20.8)
Anti-HPV 45 cLIA ≥21 mMU/mL	100.0 (91.8 to 100.0)	13.3 (5.1 to 26.8)
Anti-HPV 52 cLIA ≥30 mMU/mL	95.6 (84.9 to 99.5)	7.0 (1.5 to 19.1)
Anti-HPV 58 cLIA ≥31 mMU/mL	100.0 (92.6 to 100.0)	0.0 (0.0 to 8.2)

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Up to approximately 55 months

Adverse event reporting additional description

All-cause mortality included all the randomized participants. Non-serious and serious adverse events were reported on all Participants as Treated (APaT). The APaT population consists of all randomized participants who received at least 1 dose of the V503 or placebo and have provided safety data at any time during the study.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

28.0

Reporting group title

Base Study: V503

Reporting group description

Participants received an IM injection of V503 at Day 1, Month 2, and Month 6.

Reporting group title

Base Study: Placebo → Open Label V503 Extension Study

Reporting group description

Participants from the placebo arm of the base study who did not complete the 3-dose series received 3 doses of V503 on Day 1, Month 2 and Month 6 of the open label extension study.

Reporting group title

Base Study: V503 → Open Label V503 Extension Study

Reporting group description

Participants from the V503 arm of the base study who did not complete the 3-dose series received 1 or 2 doses of V503, on Day 1, or Day 1 and Month 4 of the open label extension study.

Reporting group title

Base Study: Placebo

Reporting group description

Participants received an IM injection of placebo at Day 1, Month 2, and Month 6.

Serious adverse events	Base Study: V503	Base Study: Placebo → Open Label V503 Extension Study	Base Study: V503 → Open Label V503 Extension Study	Base Study: Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 529 (1.32%)	2 / 381 (0.52%)	0 / 2 (0.00%)	5 / 530 (0.94%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts
subjects affected / exposed	0 / 529 (0.00%)	0 / 381 (0.00%)	0 / 2 (0.00%)	1 / 530 (0.19%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Tendon rupture
subjects affected / exposed	0 / 529 (0.00%)	0 / 381 (0.00%)	0 / 2 (0.00%)	1 / 530 (0.19%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	0 / 529 (0.00%)	0 / 381 (0.00%)	0 / 2 (0.00%)	1 / 530 (0.19%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Brain contusion
subjects affected / exposed	1 / 529 (0.19%)	0 / 381 (0.00%)	0 / 2 (0.00%)	0 / 530 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ankle fracture
subjects affected / exposed	0 / 529 (0.00%)	1 / 381 (0.26%)	0 / 2 (0.00%)	0 / 530 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Colitis ulcerative
subjects affected / exposed	1 / 529 (0.19%)	0 / 381 (0.00%)	0 / 2 (0.00%)	0 / 530 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pneumothorax
subjects affected / exposed	1 / 529 (0.19%)	0 / 381 (0.00%)	0 / 2 (0.00%)	0 / 530 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 529 (0.19%)	0 / 381 (0.00%)	0 / 2 (0.00%)	1 / 530 (0.19%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	1 / 529 (0.19%)	0 / 381 (0.00%)	0 / 2 (0.00%)	1 / 530 (0.19%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Campylobacter gastroenteritis
subjects affected / exposed	1 / 529 (0.19%)	0 / 381 (0.00%)	0 / 2 (0.00%)	0 / 530 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 529 (0.00%)	0 / 381 (0.00%)	0 / 2 (0.00%)	1 / 530 (0.19%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic tonsillitis
subjects affected / exposed	1 / 529 (0.19%)	0 / 381 (0.00%)	0 / 2 (0.00%)	0 / 530 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural infection
subjects affected / exposed	0 / 529 (0.00%)	0 / 381 (0.00%)	0 / 2 (0.00%)	1 / 530 (0.19%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 529 (0.00%)	1 / 381 (0.26%)	0 / 2 (0.00%)	0 / 530 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Base Study: V503	Base Study: Placebo → Open Label V503 Extension Study	Base Study: V503 → Open Label V503 Extension Study	Base Study: Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	374 / 529 (70.70%)	0 / 381 (0.00%)	0 / 2 (0.00%)	183 / 530 (34.53%)
General disorders and administration site conditions
Injection site erythema
subjects affected / exposed	104 / 529 (19.66%)	0 / 381 (0.00%)	0 / 2 (0.00%)	70 / 530 (13.21%)
occurrences all number	149	0	0	101
Pyrexia
subjects affected / exposed	29 / 529 (5.48%)	0 / 381 (0.00%)	0 / 2 (0.00%)	33 / 530 (6.23%)
occurrences all number	35	0	0	36
Injection site swelling
subjects affected / exposed	118 / 529 (22.31%)	0 / 381 (0.00%)	0 / 2 (0.00%)	40 / 530 (7.55%)
occurrences all number	164	0	0	50
Injection site pain
subjects affected / exposed	360 / 529 (68.05%)	0 / 381 (0.00%)	0 / 2 (0.00%)	122 / 530 (23.02%)
occurrences all number	739	0	0	166

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

19 Sep 2022

The major change of Amendment 1 (AM1) was to change the Sponsor entity name and address change and to add the capability to enroll underrepresented groups.

05 Dec 2023

The major change of AM2 was to add the extension study.

24 Sep 2024

The major change of AM3 was to conduct final efficacy analysis before end of study.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 3, randomized, placebo-controlled clinical study to evaluate the efficacy, immunogenicity and safety of the 9vHPV vaccine in Japanese males, 16 to 26 years of age.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants with ≥1 systemic AE

Primary: Percentage of participants with ≥1 systemic AE

Primary: Combined incidence of HPV 6/11/16/18-related anogenital persistent infection

Primary: Combined incidence of HPV 6/11/16/18-related anogenital persistent infection

Primary: Percentage of participants with solicited injection-site adverse events (AEs)

Primary: Percentage of participants with solicited injection-site adverse events (AEs)

Primary: Number of Participants with Elevated Oral Body Temperature

Primary: Number of Participants with Elevated Oral Body Temperature

Primary: Percentage of participants with ≥1 SAEs

Primary: Percentage of participants with ≥1 SAEs

Secondary: Combined incidence of HPV 31/33/45/52/58-related anogenital persistent infection

Secondary: Combined incidence of HPV 31/33/45/52/58-related anogenital persistent infection

Secondary: Geometric mean titers (GMTs) to HPV 6/11/16/18/31/33/45/52/58

Secondary: Geometric mean titers (GMTs) to HPV 6/11/16/18/31/33/45/52/58

Secondary: GMTs to HPV 6/11/16/18/31/33/45/52/58 - Heterosexual Males (HM) Participant Subgroup

Secondary: GMTs to HPV 6/11/16/18/31/33/45/52/58 - Heterosexual Males (HM) Participant Subgroup

Secondary: GMTs to HPV 6/11/16/18/31/33/45/52/58 - Males Who Have Sex with Males (MSM) Participant Subgroup

Secondary: GMTs to HPV 6/11/16/18/31/33/45/52/58 - Males Who Have Sex with Males (MSM) Participant Subgroup

Secondary: Percentage of Participants with Seroconversion to HPV 6/11/16/18/31/33/45/52/58

Secondary: Percentage of Participants with Seroconversion to HPV 6/11/16/18/31/33/45/52/58

Secondary: Percentage of Participants with Seroconversion to HPV 6/11/16/18/31/33/45/52/58 - HM Participant Subgroup

Secondary: Percentage of Participants with Seroconversion to HPV 6/11/16/18/31/33/45/52/58 - HM Participant Subgroup

Secondary: Percentage of Participants with Seroconversion to HPV 6/11/16/18/31/33/45/52/58 - MSM Participant Subgroup

Secondary: Percentage of Participants with Seroconversion to HPV 6/11/16/18/31/33/45/52/58 - MSM Participant Subgroup

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, randomized, placebo-controlled clinical study to evaluate the efficacy, immunogenicity and safety of the 9vHPV vaccine in Japanese males, 16 to 26 years of age.