An Investigational Study of Gardasil™ (qHPV Vaccine) in Reducing the Incidence of Anogenital Warts in Young Men (V501-020)

• ClinicalTrials.gov Identifier: NCT00090285
• Recruitment Status: Completed
• First Posted: August 27, 2004
• Results First Posted: November 19, 2009
• Last Update Posted: August 23, 2018
• 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: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Condylomata Acuminata
• Interventions: Biological: (Gardasil™) human papillomavirus (types 6, 11, 16, 18) recombinant vaccine; Biological: Comparator: placebo (unspecified)
• Enrollment: 4065

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 4164 participants were screened and 4065 were randomized

Arm/Group Title	qHPV Vaccine in Base Study	Placebo in Base Study	EXT1: Placebo in Base Study	EXT1: Incomplete qHPV Regimen in Base Study	LTFU (EXT2): Early Vaccination Group	LTFU (EXT2): Catch-up Vaccination Group
Arm/Group Description	The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received quadrivalent human papillomavirus (qHPV) vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.	The Vaccination Period for the Base study encompassed Day 1 through Month 7, during which time participants received placebo at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.	Participants in the placebo arm in the base study were offered 3 doses of open-label qHPV vaccine at Extension 1 (EXT1) Day 1, Month 2 and Month 6. Participants were followed to EXT1 Month 7.	Participants who received only 1 dose of qHPV vaccine in the Base Study were offered a complete 3-dose qHPV vaccine regimen (administered at EXT1 Day 1, Month 2 and Month 6). Participants who received only 2 doses of qHPV vaccine in the Base Study were offered a single additional dose of qHPV vaccine (administered at EXT1 Day 1). Participants were followed to EXT1 Month 7.	Participants received ≥1 dose of qHPV vaccine in Base Study and were followed up to a total of 10 years after their first dose of qHPV vaccine. No vaccinations were administered during Long-term Follow-up (LTFU) (EXT2).	Participants received placebo in Base Study and qHPV vaccine in EXT1 and were followed up to a total of 7 years after their first dose of qHPV vaccine. No vaccinations were administered during LTFU (EXT2).
Period Title: Base Study Vaccination Period
Started	2032	2033	0	0	0	0
Vaccinated	2025	2030	0	0	0	0
Completed	1818	1814	0	0	0	0
Not Completed	214	219	0	0	0	0
Reason Not Completed
Randomized Not Vaccinated	7	3	0	0	0	0
Adverse Event	2	4	0	0	0	0
Lost to Follow-up	111	112	0	0	0	0
Protocol Violation	2	3	0	0	0	0
Withdrawal by Subject	64	69	0	0	0	0
Uncooperative	2	2	0	0	0	0
Moved	20	21	0	0	0	0
Site Terminated	1	0	0	0	0	0
Other	2	2	0	0	0	0
Subject Incarcerated	2	2	0	0	0	0
HIV positive	1	1	0	0	0	0
Period Title: Base Study Follow-up Period
Started	1822 [1]	1821 [2]	0	0	0	0
Completed	1487	1479	0	0	0	0
Not Completed	335	342	0	0	0	0
Reason Not Completed
Adverse Event	3	10	0	0	0	0
Lost to Follow-up	232	226	0	0	0	0
Withdrawal by Subject	53	64	0	0	0	0
Moved	41	36	0	0	0	0
Other	2	0	0	0	0	0
Protocol Violation	1	0	0	0	0	0
Uncooperative	3	4	0	0	0	0
Subject Incarcerated	0	2	0	0	0	0
[1] 4 subjects who did not receive 3 doses of vaccine in base study continued into the Follow-up Period; [2] 7 subjects who did not receive 3 doses of placebo in base study continued into the Follow-up Period
Period Title: Extension 1
Started	0	0	1098 [1]	16 [1]	0	0
Completed	0	0	1041	15	0	0
Not Completed	0	0	57	1	0	0
Reason Not Completed
Adverse Event	0	0	2	0	0	0
Lost to Follow-up	0	0	35	0	0	0
Withdrawal by Subject	0	0	13	1	0	0
Other	0	0	4	0	0	0
Moved	0	0	3	0	0	0
[1] Participation in EXT1 was voluntary; not all participants eligible for EXT1 enrolled.
Period Title: Long-term Follow-up (EXT2)
Started	0	0	0	0	936 [1]	867 [1]
Completed	0	0	0	0	709	664
Not Completed	0	0	0	0	227	203
Reason Not Completed
Adverse Event	0	0	0	0	5	2
Lost to Follow-up	0	0	0	0	156	143
Withdrawal by Subject	0	0	0	0	60	53
Physician Decision	0	0	0	0	6	5
[1] Not all eligible participants enrolled in LTFU (EXT2)

Baseline Characteristics

Arm/Group Title		qHPV Vaccine in Base Study	Placebo in Base Study	Total
Arm/Group Description		The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.	The Vaccination Period for the Base study encompassed Day 1 through Month 7, during which time participants received placebo at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.	Total of all reporting groups
Overall Number of Baseline Participants		2032	2033	4065
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	2032 participants	2033 participants	4065 participants
		20.6 (2.0)	20.5 (2.0)	20.5 (2.0)
Age, Continuous [1]; Median (Full Range); Unit of measure: Years
	Number Analyzed	2032 participants	2033 participants	4065 participants
		20; (16 to 26)	20; (15 to 27)	20; (15 to 27)
		[1] Measure Description: Although the upper age limit for this study was 26 years old, one subject age 27 was randomized into the study.
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2032 participants	2033 participants	4065 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	2032 100.0%	2033 100.0%	4065 100.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	2032 participants	2033 participants	4065 participants
Asian		201	205	406
Black		405	400	805
Hispanic American		412	423	835
Native American		1	2	3
White		719	712	1431
Multi-Racial		291	283	574
Indian (subcontinent)		1	8	9
Polynesian		2	0	2

Outcome Measures

1. Primary Outcome

Title	Base Study: Incidence of Human Papillomavirus (HPV) Type 6/11/16/18-related External Genital Warts, Penile/Perianal/Perineal Intraepithelial Neoplasia (PIN), Penile, Perianal or Perineal Cancer
Description	Participants with HPV 6/11/16/18-related external genital warts, penile/perianal/perineal intraepithelial neoplasia (PIN), penile, perianal or perineal cancer per 100 person-years of follow-up was assessed.
Time Frame	Base study: through Month 36

Outcome Measure Data

Analysis Population Description

Participants must have received 3 doses of qHPV vaccine or placebo, have no protocol violations that could interfere with the effects of the vaccine, be seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, and must provide data after Month 7.

Arm/Group Title	qHPV Vaccine in Base Study	Placebo in Base Study
Arm/Group Description:	The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.	The Vaccination Period for the Base study encompassed Day 1 through Month 7, during which time participants received placebo at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.
Overall Number of Participants Analyzed	1394	1404
Measure Type: Number; Unit of Measure: Incidence per 100 person-years
	0.1	1.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	qHPV Vaccine in Base Study, Placebo in Base Study
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	90.6
	Confidence Interval	95%; 70.1 to 98.2
	Estimation Comments	Confidence Interval (CI) based on binomial tail probabilities and not from a dispersion parameter.

2. Primary Outcome

Title	Overall Study: Incidence of HPV Type 6/11-related Genital Warts
Description	Incidence of HPV Type 6/11-related genital warts is expressed as events per 10,000 person-years of follow-up.
Time Frame	Up to 10 years after the first dose of qHPV vaccine

Outcome Measure Data

Analysis Population Description

Participants must have received 3 doses of qHPV vaccine, have no protocol violations that could interfere with the effects of the vaccine, be seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, and must provide data after Month 7. This endpoint applied only to participants in the Base Study qHPV vaccine group.

Arm/Group Title	qHPV Vaccine in Base Study
Arm/Group Description:	The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6.
Overall Number of Participants Analyzed	1243
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Incidence per 10,000 person-years
	4.3; (0.9 to 12.5)

3. Primary Outcome

Title	Overall Study: Incidence of HPV Type 6/11/16/18-related External Genital Warts, PIN, Penile, Perianal or Perineal Cancer
Description	Incidence of HPV Type 6/11/16/18-related external genital warts, PIN, penile, perianal or perineal cancer is expressed as events per 10,000 person-years of follow-up.
Time Frame	Up to 10 years after the first dose of qHPV vaccine

Outcome Measure Data

Analysis Population Description

Participants must have received 3 doses of qHPV vaccine, have no protocol violations that could interfere with the effects of the vaccine, be seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, and must provide data after Month 7. This endpoint applied only to participants in the Base Study qHPV vaccine group.

Arm/Group Title	qHPV Vaccine in Base Study
Arm/Group Description:	The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.
Overall Number of Participants Analyzed	1395
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Incidence per 10,000 person-years
	3.8; (0.8 to 11.1)

4. Primary Outcome

Title	Overall Study: Incidence of HPV Type 6/11/16/18-related Anal Intraepithelial Neoplasia (AIN) and Anal Cancer
Description	Incidence of HPV Type 6/11/16/18-related AIN and anal cancer is expressed as events per 10,000 person-years of follow-up. MSM is men having sex with men.
Time Frame	Up to 10 years after the first dose of qHPV vaccine

Outcome Measure Data

Analysis Population Description

Participants must have received 3 doses of qHPV vaccine, have no protocol violations that could interfere with the effects of the vaccine, be seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, and must provide data after Month 7. This endpoint applied only to MSM in the Base Study qHPV vaccine group.

Arm/Group Title	MSM qHPV Vaccine in Base Study
Arm/Group Description:	The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.
Overall Number of Participants Analyzed	194
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Incidence per 10,000 person-years
	69.3; (25.4 to 150.8)

5. Primary Outcome

Title	Base Study: Number of Participants With Severe Injection Site Adverse Experiences (AEs)
Description	An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR'S product, 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 SPONSOR'S product, is also an adverse experience. A severe AE is incapacitating with inability to work or do usual activities.
Time Frame	Base study: through Day 5 after any vaccination

Outcome Measure Data

Analysis Population Description

The analysis population included all vaccinated participants excluding 6 participants who received non-compliant mixed regimens of qHPV vaccine and placebo.

Arm/Group Title	qHPV Vaccine in Base Study	Placebo in Base Study
Arm/Group Description:	The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.	The Vaccination Period for the Base study encompassed Day 1 through Month 7, during which time participants received placebo at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.
Overall Number of Participants Analyzed	2020	2029
Measure Type: Count of Participants; Unit of Measure: Participants
	25 1.2%	20 1.0%

6. Primary Outcome

Title	Base Study: Number of Participants With Vaccine-Related Serious Adverse Events (SAEs)
Description	A serious adverse event is an AE that 1) results in death, 2) is life threatening, 3) results in persistent or significant disability or incapacity, 4) results in or prolongs an existing hospitalization, 5) is a congenital anomaly or birth defect, 6) is a cancer, 7) is an overdose, or 8) based on appropriate medical judgment may jeopardize the participant and may require medical or surgical intervention. A vaccine-related AE is one deemed to be possibly, probably or definitely related to study vaccine by the investigator.
Time Frame	Base study: through Month 36

Outcome Measure Data

Analysis Population Description

The analysis population included all vaccinated participants excluding 6 participants who received non-compliant mixed regimens of qHPV vaccine and placebo.

Arm/Group Title	qHPV Vaccine: Base Study and Followup	Placebo: Base Study and Followup
Arm/Group Description:	The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the base study encompassed Month 7 through Month 36. The at-risk population was participants who received ≥ 1 qHPV vaccination in the base study.	The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time participants received placebo at Day 1, Month 2 and Month 6. Follow-up for the base study encompassed Month 7 through Month 36. The at-risk population was participants who received ≥ 1 placebo injection in the base study.
Overall Number of Participants Analyzed	2020	2029
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

7. Primary Outcome

Title	LTFU (EXT2): Number of Participants With Vaccine-Related SAEs
Description	An SAE is an AE that 1) results in death, 2) is life threatening, 3) results in persistent or significant disability or incapacity, 4) results in or prolongs an existing hospitalization, 5) is a congenital anomaly or birth defect, 6) is a cancer, 7) is an overdose, or 8) based on appropriate medical judgment may jeopardize the participant and may require medical or surgical intervention. A vaccine-related AE is one deemed to be possibly, probably or definitely related to study vaccine by the investigator.
Time Frame	LTFU (EXT2): Early Vaccination Group: up to 12 years after last dose of qHPV vaccine; LTFU (EXT2) Catch-up Vaccination Group: up to 7 years after last dose of qHPV vaccine

Outcome Measure Data

Analysis Population Description

The population analyzed was all randomized participants receiving at least 1 dose of qHPV vaccine in the Base Study or EXT1 and enrolled in LTFU (EXT2).

Arm/Group Title	LTFU (EXT2): Early Vaccination Group	LTFU (EXT2): Catch-up Vaccination Group
Arm/Group Description:	Participants received ≥1 dose of qHPV vaccine in Base Study and were followed up to a total of 10 years after their first dose of qHPV vaccine. No vaccinations were administered during Long-term Follow-up (LTFU) (EXT2).	Participants received placebo in Base Study and qHPV vaccine in EXT1 and were followed up to a total of 7 years after their first dose of qHPV vaccine. No vaccinations were administered during LTFU (EXT2).
Overall Number of Participants Analyzed	936	867
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

8. Primary Outcome

Title	LTFU (EXT2): Number of Participants Who Died
Description	The number of participants who died was assessed.
Time Frame	LTFU (EXT2): Early Vaccination Group: up to 12 years after last dose of qHPV vaccine; LTFU (EXT2) Catch-up Vaccination Group: up to 7 years after last dose of qHPV vaccine

Outcome Measure Data

Analysis Population Description

The population analyzed was all randomized participants receiving at least 1 dose of qHPV vaccine in the Base Study or EXT1 and enrolled in LTFU (EXT2).

Arm/Group Title	LTFU (EXT2): Early Vaccination Group	LTFU (EXT2): Catch-up Vaccination Group
Arm/Group Description:	Participants received ≥1 dose of qHPV vaccine in Base Study and were followed up to a total of 10 years after their first dose of qHPV vaccine. No vaccinations were administered during Long-term Follow-up (LTFU) (EXT2).	Participants received placebo in Base Study and qHPV vaccine in EXT1 and were followed up to a total of 7 years after their first dose of qHPV vaccine. No vaccinations were administered during LTFU (EXT2).
Overall Number of Participants Analyzed	936	867
Measure Type: Count of Participants; Unit of Measure: Participants
	5 0.5%	2 0.2%

9. Secondary Outcome

Title	Base Study: Incidence of HPV 6/11/16/18-related Persistent Infection
Description	Participants with HPV Type 6/11/16/18-related persistent infection per 100 person-years of follow-up was assessed.
Time Frame	Base study: through Month 36

Outcome Measure Data

Analysis Population Description

Participants must have received 3 doses of qHPV vaccine or placebo, have no protocol violations that could interfere with the effects of the vaccine, be seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, and must provide data after Month 7.

Arm/Group Title	qHPV Vaccine in Base Study	Placebo in Base Study
Arm/Group Description:	The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.	The Vaccination Period for the Base study encompassed Day 1 through Month 7, during which time participants received placebo at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.
Overall Number of Participants Analyzed	1390	1402
Measure Type: Number; Unit of Measure: Infection per 100 person-years
	0.7	4.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	qHPV Vaccine in Base Study, Placebo in Base Study
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	85.5
	Confidence Interval	95%; 77.0 to 91.3
	Estimation Comments	CI based on binomial tail probabilities and not from a dispersion parameter. Hochberg multiplicity adjustment applied to the CI.

10. Secondary Outcome

Title	Base Study: Incidence of HPV 6/11/16/18-related Deoxyribonucleic Acid (DNA) Detection
Description	Participants with HPV 6/11/16/18-related DNA detection per 100 person-years of follow-up was assessed.
Time Frame	Base study: through Month 36

Outcome Measure Data

Analysis Population Description

Participants must have received 3 doses of qHPV vaccine or placebo, have no protocol violations that could interfere with the effects of the vaccine, be seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, and must provide data after Month 7.

Arm/Group Title	qHPV Vaccine in Base Study	Placebo in Base Study
Arm/Group Description:	The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.	The Vaccination Period for the Base study encompassed Day 1 through Month 7, during which time participants received placebo at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.
Overall Number of Participants Analyzed	1390	1402
Measure Type: Number; Unit of Measure: Detection per 100 person-years
	5.3	10.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	qHPV Vaccine in Base Study, Placebo in Base Study
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	51.0
	Confidence Interval	95%; 40.3 to 59.9
	Estimation Comments	CI based on binomial tail probabilities and not from a dispersion parameter. Hochberg multiplicity adjustment applied to the CI.

11. Secondary Outcome

Title	Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 7 Assessed by Competitive Luminex Immunoassay (cLIA)
Description	Antibodies to HPV types were measured using cLIA. Antibody titers were expressed as cLIA milli Merck units/mL (cLIA mMU/mL).
Time Frame	Month 7

Outcome Measure Data

Analysis Population Description

All participants who 1) were seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, 2) received all 3 vaccinations, and 3) did not have protocol deviations that could interfere with the effects of the vaccine. Immunogenicity was assessed only for participants who received qHPV vaccine in the Base Study.

Arm/Group Title		qHPV Vaccine in Base Study
Arm/Group Description:		The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.
Overall Number of Participants Analyzed		2025
Geometric Mean (95% Confidence Interval); Unit of Measure: cLIA mMU/mL
HPV Type 6	Number Analyzed	1090 participants
		447.7; (415.9 to 481.9)
HPV Type 11	Number Analyzed	1090 participants
		624.4; (588.4 to 662.6)
HPV Type 16	Number Analyzed	1133 participants
		2406.1; (2245.0 to 2578.8)
HPV Type 18	Number Analyzed	1173 participants
		402.8; (373.9 to 433.9)

12. Secondary Outcome

Title	Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 36 Assessed by cLIA
Description	Antibodies to HPV types were measured using cLIA. Antibody titers were expressed as cLIA milli Merck units/mL (cLIA mMU/mL).
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description

All participants who 1) were seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, 2) received all 3 vaccinations, and 3) did not have protocol deviations that could interfere with the effects of the vaccine. Immunogenicity was assessed only for participants who received qHPV vaccine in the Base Study.

Arm/Group Title		qHPV Vaccine in Base Study
Arm/Group Description:		The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.
Overall Number of Participants Analyzed		2025
Geometric Mean (95% Confidence Interval); Unit of Measure: cLIA mMU/mL
HPV Type 6	Number Analyzed	845 participants
		71.5; (66.7 to 76.7)
HPV Type 11	Number Analyzed	845 participants
		82.5; (77.0 to 88.5)
HPV Type 16	Number Analyzed	875 participants
		293.6; (271.6 to 317.4)
HPV Type 18	Number Analyzed	904 participants
		33.2; (30.2 to 36.4)

13. Secondary Outcome

Title	Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 72 Assessed by cLIA
Description	Antibodies to HPV types were measured using cLIA. Antibody titers were expressed as cLIA milli Merck units/mL (cLIA mMU/mL).
Time Frame	Month 72

Outcome Measure Data

Analysis Population Description

All participants who 1) were seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, 2) received all 3 vaccinations, and 3) did not have protocol deviations that could interfere with the effects of the vaccine. Immunogenicity was assessed only for participants who received qHPV vaccine in the Base Study.

Arm/Group Title		qHPV Vaccine in Base Study
Arm/Group Description:		The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study was through Month 36 and for LTFU (EXT2) was through Month 120.
Overall Number of Participants Analyzed		2025
Geometric Mean (95% Confidence Interval); Unit of Measure: cLIA mMU/mL
HPV Type 6	Number Analyzed	575 participants
		57.2; (52.3 to 62.5)
HPV Type 11	Number Analyzed	575 participants
		62.1; (56.7 to 68.1)
HPV Type 16	Number Analyzed	609 participants
		249.4; (225.6 to 275.8)
HPV Type 18	Number Analyzed	633 participants
		25.9; (23.2 to 28.9)

14. Secondary Outcome

Title	Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by cLIA
Description	Antibodies to HPV types were measured using cLIA. Antibody titers were expressed as cLIA milli Merck units/mL (cLIA mMU/mL).
Time Frame	Month 120

Outcome Measure Data

Analysis Population Description

All participants who 1) were seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, 2) received all 3 vaccinations, and 3) did not have protocol deviations that could interfere with the effects of the vaccine. Immunogenicity was assessed only for participants who received qHPV vaccine in the Base Study.

Arm/Group Title		qHPV Vaccine in Base Study
Arm/Group Description:		The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study was through Month 36 and for LTFU (EXT2) was through Month 120.
Overall Number of Participants Analyzed		2025
Geometric Mean (95% Confidence Interval); Unit of Measure: cLIA mMU/mL
HPV Type 6	Number Analyzed	374 participants
		49.4; (44.1 to 55.4)
HPV Type 11	Number Analyzed	374 participants
		38.7; (34.5 to 43.5)
HPV Type 16	Number Analyzed	393 participants
		182.9; (161.4 to 207.3)
HPV Type 18	Number Analyzed	408 participants
		17.6; (15.5 to 19.9)

15. Secondary Outcome

Title	Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 7 Assessed by cLIA
Description	Antibodies to HPV types were measured using cLIA. Thresholds for seropositive were ≥20, 16, 20, and 24 cLIA mMU/mL for HPV Types 6, 11, 16, and 18, respectively.
Time Frame	Month 7

Outcome Measure Data

Analysis Population Description

All participants who 1) were seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, 2) received all 3 vaccinations, and 3) did not have protocol deviations that could interfere with the effects of the vaccine. Immunogenicity was assessed only for participants who received qHPV vaccine in the Base Study.

Arm/Group Title		qHPV Vaccine in Base Study
Arm/Group Description:		The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.
Overall Number of Participants Analyzed		2025
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
HPV Type 6	Number Analyzed	1090 participants
		98.9; (98.1 to 99.4)
HPV Type 11	Number Analyzed	1090 participants
		99.2; (98.4 to 99.6)
HPV Type 16	Number Analyzed	1133 participants
		98.8; (97.9 to 99.3)
HPV Type 18	Number Analyzed	1173 participants
		97.4; (96.3 to 98.2)

16. Secondary Outcome

Title	Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 36 Assessed by cLIA
Description	Antibodies to HPV types were measured using cLIA. Thresholds for seropositive were ≥20, 16, 20, and 24 cLIA mMU/mL for HPV Types 6, 11, 16, and 18, respectively.
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description

All participants who 1) were seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, 2) received all 3 vaccinations, and 3) did not have protocol deviations that could interfere with the effects of the vaccine. Immunogenicity was assessed only for participants who received qHPV vaccine in the Base Study.

Arm/Group Title		qHPV Vaccine in Base Study
Arm/Group Description:		The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.
Overall Number of Participants Analyzed		2025
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
HPV Type 6	Number Analyzed	845 participants
		88.9; (86.6 to 90.9)
HPV Type 11	Number Analyzed	845 participants
		94.0; (92.1 to 95.5)
HPV Type 16	Number Analyzed	875 participants
		97.9; (96.8 to 98.8)
HPV Type 18	Number Analyzed	904 participants
		57.1; (53.8 to 60.3)

17. Secondary Outcome

Title	Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 72 Assessed by cLIA
Description	Antibodies to HPV types were measured using cLIA. Thresholds for seropositive were ≥20, 16, 20, and 24 cLIA mMU/mL for HPV Types 6, 11, 16, and 18, respectively.
Time Frame	Month 72

Outcome Measure Data

Analysis Population Description

All participants who 1) were seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, 2) received all 3 vaccinations, and 3) did not have protocol deviations that could interfere with the effects of the vaccine. Immunogenicity was assessed only for participants who received qHPV vaccine in the Base Study.

Arm/Group Title		qHPV Vaccine in Base Study
Arm/Group Description:		The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study was through Month 36 and for LTFU (EXT2) was through Month 120.
Overall Number of Participants Analyzed		2025
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
HPV Type 6	Number Analyzed	575 participants
		84.3; (81.1 to 87.2)
HPV Type 11	Number Analyzed	575 participants
		88.0; (85.1 to 90.5)
HPV Type 16	Number Analyzed	609 participants
		97.0; (95.4 to 98.2)
HPV Type 18	Number Analyzed	633 participants
		49.6; (45.6 to 53.6)

18. Secondary Outcome

Title	Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by cLIA
Description	Antibodies to HPV types were measured using cLIA. Thresholds for seropositive were ≥20, 16, 20, and 24 cLIA mMU/mL for HPV Types 6, 11, 16, and 18, respectively.
Time Frame	Month 120

Outcome Measure Data

Analysis Population Description

All participants who 1) were seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, 2) received all 3 vaccinations, and 3) did not have protocol deviations that could interfere with the effects of the vaccine. Immunogenicity was assessed only for participants who received qHPV vaccine in the Base Study.

Arm/Group Title		qHPV Vaccine in Base Study
Arm/Group Description:		The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study was through Month 36 and for LTFU (EXT2) was through Month 120.
Overall Number of Participants Analyzed		2025
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
HPV Type 6	Number Analyzed	374 participants
		79.1; (74.7 to 83.2)
HPV Type 11	Number Analyzed	374 participants
		79.9; (75.5 to 83.9)
HPV Type 16	Number Analyzed	393 participants
		94.9; (92.2 to 96.9)
HPV Type 18	Number Analyzed	408 participants
		40.2; (35.4 to 45.1)

19. Secondary Outcome

Title	Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA)
Description	Antibodies to HPV types were measured using Luminex immunoassay (IgG-LIA). The unit of measure for this assay is IgG LIA mMU/mL; this unit cannot be directly compared with the cLIA mMU/mL unit reported for the cLIA results.
Time Frame	Month 120

Outcome Measure Data

Analysis Population Description

All participants who 1) were seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, 2) received all 3 vaccinations, and 3) did not have protocol deviations that could interfere with the effects of the vaccine. Immunogenicity was assessed only for participants who received qHPV vaccine in the Base Study.

Arm/Group Title		qHPV Vaccine in Base Study
Arm/Group Description:		The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study was through Month 36 and for LTFU (EXT2) was through Month 120.
Overall Number of Participants Analyzed		2025
Geometric Mean (95% Confidence Interval); Unit of Measure: IgG LIA mMU/mL
HPV Type 6	Number Analyzed	278 participants
		38.8; (34.0 to 44.2)
HPV Type 11	Number Analyzed	274 participants
		31.0; (27.2 to 35.3)
HPV Type 16	Number Analyzed	291 participants
		162.0; (141.2 to 185.7)
HPV Type 18	Number Analyzed	305 participants
		19.7; (17.0 to 22.9)

20. Secondary Outcome

Title	Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by IgG LIA
Description	Antibodies to HPV types were measured using IgG LIA. Thresholds for seropositive were ≥9, 6, 5, and 5 IgG LIA mMU/mL for HPV Types 6, 11, 16, and 18, respectively.
Time Frame	Month 120

Outcome Measure Data

Analysis Population Description

All participants who 1) were seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, 2) received all 3 vaccinations, and 3) did not have protocol deviations that could interfere with the effects of the vaccine. Immunogenicity was assessed only for participants who received qHPV vaccine in the Base Study..

Arm/Group Title		qHPV Vaccine in Base Study
Arm/Group Description:		The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study was through Month 36 and for LTFU (EXT2) was through Month 120.
Overall Number of Participants Analyzed		2025
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
HPV Type 6	Number Analyzed	278 participants
		91.7; (87.8 to 94.7)
HPV Type 11	Number Analyzed	274 participants
		92.0; (88.1 to 94.9)
HPV Type 16	Number Analyzed	291 participants
		99.7; (98.1 to 100)
HPV Type 18	Number Analyzed	305 participants
		92.1; (88.5 to 94.9)

21. Other Pre-specified Outcome

Title	Base Study: Substudy to Evaluate the Incidence of HPV 6/11/16/18-related Anal Intraepithelial Neoplasia (AIN) and Anal Cancer in Men Having Sex With Men (MSM)
Description	Participants with HPV 6/11/16/18-related AIN or anal cancer per 100 person-years of follow-up was assessed.
Time Frame	Base study: through Month 36

Outcome Measure Data

Analysis Population Description

Only a subset of participants was included for this sub-study. Participants must have received 3 doses of qHPV vaccine or placebo, have no protocol violations that could interfere with the effects of the vaccine, be seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, and must provide data after Month 7.

Arm/Group Title	qHPV Vaccine in Base Study	Placebo in Base Study
Arm/Group Description:	The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.	The Vaccination Period for the Base study encompassed Day 1 through Month 7, during which time participants received placebo at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.
Overall Number of Participants Analyzed	194	208
Measure Type: Number; Unit of Measure: Incidence per 100 person-years
	1.3	5.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	qHPV Vaccine in Base Study, Placebo in Base Study
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	77.5
	Confidence Interval	95%; 39.6 to 93.3
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Base study: all AEs were collected systematically from Day 1 through Month 36. EXT 1: SAEs were collected systematically from Day 1 through Month 7. LTFU (EXT2): deaths and vaccine-related SAEs were collected up to 12 years after last dose of qHPV vaccine in Early Vaccination Group and up to 7 years after last dose of qHPV in Catch-up Vaccination Group.
Adverse Event Reporting Description	Medical Dictionary for Regulatory Activities (MedDRA) version 12.0 was used during the base study and follow-up, MedDRA version 14.1 was used during EXT1, and MedDRA version 20.0 was used during LTFU (EXT2). Participants at risk in EXT1 received ≥1 qHPV vaccination in EXT1 and had follow-up data. Other AEs were not solicited during EXT1 or LTFU (EXT2).
Arm/Group Title	qHPV Vaccine: Base Study		Placebo: Base Study		qHPV Vaccine: EXT1		LTFU (EXT2)
Arm/Group Description	The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6.		The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time participants received placebo at Day 1, Month 2 and Month 6.		Participants who received placebo and participants who received only 1 dose of qHPV vaccine in the base study were offered a complete 3-dose qHPV vaccine regimen (administered at EXT1 Day 1, Month 2 and Month 6). Participants who received only 2 doses of qHPV vaccine in the base study were offered a single additional dose of qHPV vaccine (administered at EXT1 Day 1).		Participants received ≥1 dose of qHPV vaccine in Base Study, or received placebo in Base Study and qHPV vaccine in EXT1. This arm includes both groups enrolled in LTFU (EXT2): Early Vaccination Group and Catch-up Vaccination Group.
All-Cause Mortality
	qHPV Vaccine: Base Study		Placebo: Base Study		qHPV Vaccine: EXT1		LTFU (EXT2)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	3/2020 (0.15%)		10/2029 (0.49%)		2/1084 (0.18%)		7/1803 (0.39%)
Serious Adverse Events
	qHPV Vaccine: Base Study		Placebo: Base Study		qHPV Vaccine: EXT1		LTFU (EXT2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/2020 (0.40%)		11/2029 (0.54%)		3/1084 (0.28%)		7/1803 (0.39%)
Cardiac disorders
Cardiac arrest †	1/2020 (0.05%)	1	0/2029 (0.00%)	0	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Myocardial ischaemia †	0/2020 (0.00%)	0	1/2029 (0.05%)	1	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Pericardial haemorrhage †	0/2020 (0.00%)	0	1/2029 (0.05%)	1	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Myocardial infarction †	0/2020 (0.00%)	0	0/2029 (0.00%)	0	0/1084 (0.00%)	0	1/1803 (0.06%)	1
General disorders
Non-cardiac chest pain †	1/2020 (0.05%)	1	0/2029 (0.00%)	0	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Immune system disorders
Hypersensitivity †	1/2020 (0.05%)	1	0/2029 (0.00%)	0	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Infections and infestations
Appendicitis †	1/2020 (0.05%)	1	0/2029 (0.00%)	0	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Cellulitis †	1/2020 (0.05%)	1	0/2029 (0.00%)	0	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Varicella †	1/2020 (0.05%)	1	0/2029 (0.00%)	0	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Pneumonia †	0/2020 (0.00%)	0	0/2029 (0.00%)	0	1/1084 (0.09%)	1	1/1803 (0.06%)	1
HIV infection †	0/2020 (0.00%)	0	0/2029 (0.00%)	0	0/1084 (0.00%)	0	1/1803 (0.06%)	1
Injury, poisoning and procedural complications
Accidental overdose †	0/2020 (0.00%)	0	1/2029 (0.05%)	1	1/1084 (0.09%)	1	0/1803 (0.00%)	0
Cervical vertebral fracture †	1/2020 (0.05%)	1	0/2029 (0.00%)	0	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Chemical poisoning †	0/2020 (0.00%)	0	1/2029 (0.05%)	1	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Contusion †	0/2020 (0.00%)	0	1/2029 (0.05%)	1	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Gun shot wound †	1/2020 (0.05%)	1	3/2029 (0.15%)	3	1/1084 (0.09%)	1	1/1803 (0.06%)	1
Head injury †	0/2020 (0.00%)	0	1/2029 (0.05%)	1	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Multiple drug overdose †	0/2020 (0.00%)	0	1/2029 (0.05%)	1	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Road traffic accident †	1/2020 (0.05%)	1	1/2029 (0.05%)	1	0/1084 (0.00%)	0	1/1803 (0.06%)	1
Traumatic brain injury †	1/2020 (0.05%)	1	0/2029 (0.00%)	0	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Traumatic intracranial haemorrhage †	1/2020 (0.05%)	1	0/2029 (0.00%)	0	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Blast injury †	0/2020 (0.00%)	0	0/2029 (0.00%)	0	0/1084 (0.00%)	0	1/1803 (0.06%)	1
Burns second degree †	0/2020 (0.00%)	0	0/2029 (0.00%)	0	0/1084 (0.00%)	0	1/1803 (0.06%)	1
Craniocerebral injury †	0/2020 (0.00%)	0	0/2029 (0.00%)	0	0/1084 (0.00%)	0	1/1803 (0.06%)	1
Subarachnoid haemorrhage †	0/2020 (0.00%)	0	0/2029 (0.00%)	0	0/1084 (0.00%)	0	1/1803 (0.06%)	1
Metabolism and nutrition disorders
Metabolic acidosis †	0/2020 (0.00%)	0	0/2029 (0.00%)	0	0/1084 (0.00%)	0	1/1803 (0.06%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroma †	0/2020 (0.00%)	0	0/2029 (0.00%)	0	0/1084 (0.00%)	0	1/1803 (0.06%)	1
Nervous system disorders
Convulsion †	1/2020 (0.05%)	1	0/2029 (0.00%)	0	0/1084 (0.00%)	0	0/1803 (0.00%)	0
Cerebral haemorrhage †	0/2020 (0.00%)	0	0/2029 (0.00%)	0	0/1084 (0.00%)	0	1/1803 (0.06%)	1
Psychiatric disorders
Completed suicide †	0/2020 (0.00%)	0	2/2029 (0.10%)	2	0/1084 (0.00%)	0	0/1803 (0.00%)	0
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	qHPV Vaccine: Base Study		Placebo: Base Study		qHPV Vaccine: EXT1		LTFU (EXT2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1277/2020 (63.22%)		1183/2029 (58.30%)		0/0		0/0
Gastrointestinal disorders
Abdominal pain upper †	19/2020 (0.94%)	21	23/2029 (1.13%)	23	0/0	0	0/0	0
Diarrhoea †	40/2020 (1.98%)	44	36/2029 (1.77%)	38	0/0	0	0/0	0
Nausea †	27/2020 (1.34%)	30	16/2029 (0.79%)	16	0/0	0	0/0	0
General disorders
Pyrexia †	118/2020 (5.84%)	131	125/2029 (6.16%)	149	0/0	0	0/0	0
Injection Site Erythema †	304/2020 (15.05%)	446	275/2029 (13.55%)	384	0/0	0	0/0	0
Injection Site Pain †	1116/2020 (55.25%)	2087	992/2029 (48.89%)	1767	0/0	0	0/0	0
Injection Site Pruritus †	23/2020 (1.14%)	27	24/2029 (1.18%)	29	0/0	0	0/0	0
Injection Site Swelling †	219/2020 (10.84%)	318	187/2029 (9.22%)	270	0/0	0	0/0	0
Infections and infestations
Influenza †	42/2020 (2.08%)	43	44/2029 (2.17%)	47	0/0	0	0/0	0
Nasopharyngitis †	44/2020 (2.18%)	46	50/2029 (2.46%)	59	0/0	0	0/0	0
Pharyngitis †	22/2020 (1.09%)	23	20/2029 (0.99%)	21	0/0	0	0/0	0
Upper respiratory tract infection †	27/2020 (1.34%)	28	20/2029 (0.99%)	22	0/0	0	0/0	0
Nervous system disorders
Headache †	179/2020 (8.86%)	222	207/2029 (10.20%)	275	0/0	0	0/0	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain †	38/2020 (1.88%)	38	37/2029 (1.82%)	37	0/0	0	0/0	0
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Vice President, Late Stage Development Group Leader
• Organization: Merck Sharp & Dohme Corp.
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Goldstone SE, Giuliano AR, Palefsky JM, Lazcano-Ponce E, Penny ME, Cabello RE, Moreira ED Jr, Baraldi E, Jessen H, Ferenczy A, Kurman R, Ronnett BM, Stoler MH, Bautista O, Das R, Group T, Luxembourg A, Zhou HJ, Saah A. Efficacy, immunogenicity, and safety of a quadrivalent HPV vaccine in men: results of an open-label, long-term extension of a randomised, placebo-controlled, phase 3 trial. Lancet Infect Dis. 2022 Mar;22(3):413-425. doi: 10.1016/S1473-3099(21)00327-3. Epub 2021 Nov 12.

Tota JE, Giuliano AR, Goldstone SE, Dubin B, Saah A, Luxembourg A, Velicer C, Palefsky JM. Anogenital Human Papillomavirus (HPV) Infection, Seroprevalence, and Risk Factors for HPV Seropositivity Among Sexually Active Men Enrolled in a Global HPV Vaccine Trial. Clin Infect Dis. 2022 Apr 9;74(7):1247-1256. doi: 10.1093/cid/ciab603. Erratum In: Clin Infect Dis. 2023 Jan 04;:

Doshi P, Bourgeois F, Hong K, Jones M, Lee H, Shamseer L, Spence O, Jefferson T. Adjuvant-containing control arms in pivotal quadrivalent human papillomavirus vaccine trials: restoration of previously unpublished methodology. BMJ Evid Based Med. 2020 Dec;25(6):213-219. doi: 10.1136/bmjebm-2019-111331. Epub 2020 Mar 17.

Goldstone SE, Jessen H, Palefsky JM, Giuliano AR, Moreira ED Jr, Vardas E, Aranda C, Hillman RJ, Ferris DG, Coutlee F, Marshall JB, Vuocolo S, Haupt RM, Guris D, Garner E. Quadrivalent HPV vaccine efficacy against disease related to vaccine and non-vaccine HPV types in males. Vaccine. 2013 Aug 20;31(37):3849-55. doi: 10.1016/j.vaccine.2013.06.057. Epub 2013 Jul 2.

Palefsky JM, Giuliano AR, Goldstone S, Moreira ED Jr, Aranda C, Jessen H, Hillman R, Ferris D, Coutlee F, Stoler MH, Marshall JB, Radley D, Vuocolo S, Haupt RM, Guris D, Garner EI. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med. 2011 Oct 27;365(17):1576-85. doi: 10.1056/NEJMoa1010971.

Giuliano AR, Palefsky JM, Goldstone S, Moreira ED Jr, Penny ME, Aranda C, Vardas E, Moi H, Jessen H, Hillman R, Chang YH, Ferris D, Rouleau D, Bryan J, Marshall JB, Vuocolo S, Barr E, Radley D, Haupt RM, Guris D. Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males. N Engl J Med. 2011 Feb 3;364(5):401-11. doi: 10.1056/NEJMoa0909537. Erratum In: N Engl J Med. 2011 Apr 14;364(15):1481.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00090285
• Other Study ID Numbers: V501-020; Formerly-0904HPVHMES; 2004_103; 2004-002945-10 ( EudraCT Number ); V501-020 ( Other Identifier: Merck Protocol Number )
• First Submitted: August 25, 2004
• First Posted: August 27, 2004
• Results First Submitted: October 14, 2009
• Results First Posted: November 19, 2009
• Last Update Posted: August 23, 2018