A Study of Gardasil (V501) in Preadolescents and Adolescents (V501-018)

• ClinicalTrials.gov Identifier: NCT00092547
• Recruitment Status: Completed
• First Posted: September 28, 2004
• Results First Posted: May 4, 2010
• Last Update Posted: February 20, 2018
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Conditions: Human; Papillomavirus Infections
• Interventions: Biological: V501; Biological: Comparator: Placebo
• Enrollment: 1781

Participant Flow

Recruitment Details	1781 participants were randomized to receive qHPV or Placebo in the Base Study. At month 30, participants who received Placebo in the Base Study were eligible to receive qHPV, and formed the Extension Group. Participants were to be followed for safety and efficacy for up to 10 years.
Pre-assignment Details

Arm/Group Title	qHPV Vaccine in Base Study	Placebo in Base Study	qHPV Vaccine in Extension Study
Arm/Group Description	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6.	Represents participants who were randomized into the Placebo Group, who received three 0.5 mL intramuscular injections of placebo at Day 1, Month 2, and Month 6.	Represent participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36.
Period Title: Base Vaccine Phase (Day 1 to Month 7)
Started	1184	597	0
Vaccinated	1179	596	0
Completed	1121	561	0
Not Completed	63	36	0
Reason Not Completed
Not Vaccinated	5	1	0
Adverse Event	4	1	0
Lost to Follow-up	18	7	0
Withdrawal by Subject	28	21	0
Moved	3	1	0
per sponsor request: (noncompliant)	0	1	0
Did not meet local regulations	0	1	0
Refused Vaccination	5	3	0
Period Title: Base Follow-up Phase (Month 7 to 18)
Started	1128 [1]	565 [1]	0
Completed	1108	551	0
Not Completed	20	14	0
Reason Not Completed
Subject moved	1	5	0
Withdrawal by Subject	4	2	0
Lost to Follow-up	13	7	0
Protocol Violation	1	0	0
Physician Decision	1	0	0
[1] Includes participants continuing and who previously discontinued who re-entered the study
Period Title: Base Follow-up Phase (Month 18 to 30)
Started	964 [1]	490 [1]	0
Completed	956	485	0
Not Completed	8	5	0
Reason Not Completed
Subject moved	4	2	0
Withdrawal by Subject	1	3	0
Lost to Follow-up	2	0	0
Protocol Violation	1	0	0
[1] Includes participants continuing and who previously discontinued who re-entered the study
Period Title: Extension Vaccine Phase (Month 30 to 37)
Started	956 [1]	0	485 [1]
Vaccinated in Extension Study	0	0	482
Completed	933	0	469
Not Completed	23	0	16
Reason Not Completed
Subject moved	3	0	0
Withdrawal by Subject	6	0	9
Lost to Follow-up	14	0	7
[1] Includes participants continuing and who previously discontinued who re-entered the study
Period Title: Long-term Follow-up (Month 42 Visit)
Started	612 [1]	0	308 [1]
Completed	611	0	308
Not Completed	1	0	0
Reason Not Completed
Adverse Event	1	0	0
[1] Includes participants continuing and who previously discontinued who re-entered the study
Period Title: Long-term Follow-up (Month 72 Visit)
Started	550 [1]	0	276 [1]
Completed	550	0	276
Not Completed	0	0	0
[1] Includes participants continuing and who previously discontinued who re-entered the study
Period Title: Long-term Follow-up (Month 96 Visit)
Started	508 [1]	0	267 [1]
Completed	508	0	267
Not Completed	0	0	0
[1] Includes participants continuing and who previously discontinued who re-entered the study
Period Title: Long-term Follow-up (Month 126 Visit)
Started	454	0	211
Completed	454	0	211
Not Completed	0	0	0

Baseline Characteristics

Arm/Group Title		qHPV Vaccine in Base Study	Placebo in Base Study	Total
Arm/Group Description		Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6	Represents participants who were randomized into the Placebo Group, who received three 0.5 mL intramuscular injections of placebo at Day 1, Month 2, and Month 6	Total of all reporting groups
Overall Number of Baseline Participants		1184	597	1781
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1184 participants	597 participants	1781 participants
		11.9 (1.9)	11.8 (1.9)	11.9 (1.9)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1184 participants	597 participants	1781 participants
8 Years of Age and Under		0	0	0
9 to 16 Years of Age		1184	597	1781
17 Years of Age and Over		0	0	0
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1184 participants	597 participants	1781 participants
	Female	616 52.0%	322 53.9%	938 52.7%
	Male	568 48.0%	275 46.1%	843 47.3%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1184 participants	597 participants	1781 participants
Asian		149	70	219
Black		50	21	71
Hispanic American		260	130	390
Native American		0	1	1
White		716	369	1085
Other		9	6	15

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reporting Serious Adverse Experiences (SAEs) Through Month 18
Description	Tolerability as assessed by the number of participants with clinical adverse experiences through Month 18. A serious adverse event is any adverse event that results in death, is life threatening, results in a persistent or significant disability/incapacity, results in hospitalization or prolongs an existing hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is considered an "other important medical event" based on medical judgment.
Time Frame	Up to Month 18

Outcome Measure Data

Analysis Population Description

All participants who were vaccinated according to actual treatment received (qHPV or placebo) and had safety follow-up.

Arm/Group Title	qHPV Vaccine in Base Study	Placebo in Base Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6	Represents participants who were randomized into the Placebo Group, who received three 0.5 mL intramuscular injections of placebo at Day 1, Month 2, and Month 6
Overall Number of Participants Analyzed	1165	584
Measure Type: Number; Unit of Measure: participants
	6	0

2. Primary Outcome

Title	Number of Participants Reporting SAEs From Month 18 Through Month 37
Description	Tolerability as assessed by the number of participants with clinical adverse experiences from Month 18 through Month 37
Time Frame	Month 18 to Month 37

Outcome Measure Data

Analysis Population Description

All participants who were vaccinated according to actual treatment received (qHPV or placebo) and had safety follow-up.

Arm/Group Title	qHPV Vaccine in Base Study	qHPV Vaccine in Extension Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6	Represent participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36.
Overall Number of Participants Analyzed	923	477
Measure Type: Number; Unit of Measure: participants
	0	3

3. Primary Outcome

Title	Number of Participants Reporting Other (Non-serious) AEs Through Month 18
Description	Tolerability as assessed by the number of participants with clinical adverse experiences through Month 18
Time Frame	Up to Month 18: Injection site AEs were collected from Days 1-5 and other non-serious AEs from Days 1-15 after any vaccination

Outcome Measure Data

Analysis Population Description

All participants who were vaccinated according to actual treatment received (qHPV or placebo) and had safety follow-up.

Arm/Group Title	qHPV Vaccine in Base Study	Placebo in Base Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6	Represents participants who were randomized into the Placebo Group, who received three 0.5 mL intramuscular injections of placebo at Day 1, Month 2, and Month 6
Overall Number of Participants Analyzed	1165	584
Measure Type: Number; Unit of Measure: participants
	918	340

4. Primary Outcome

Title	Percentage of Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 72
Description	A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18.
Time Frame	Month 72 (66 Months Post-dose 3 for the Original qHPV Vaccine Cohort and 36 months Post-dose 3 for the Extension Group)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 vaccinations, were seronegative to the respective HPV type at Day 1 (for the Base Vaccination group), or Month 30 (for the Extension Group), and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study	qHPV Vaccine in Extension Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6	Represent participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36.
Overall Number of Participants Analyzed	550	276
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Type 6: n=475, 151	93.3; (90.6 to 95.3)	91.4; (85.7 to 95.3)
Type 11: n=475, 151	96.0; (93.8 to 97.6)	96.7; (92.4 to 98.9)
Type 16: n=473, 154	97.9; (96.1 to 99.0)	97.4; (93.5 to 99.3)
Type 18: n=477, 160	74.4; (70.3 to 78.3)	79.4; (72.3 to 85.4)

5. Primary Outcome

Title	Geometric Mean Titers (GMTs) for Anti-HPV 6, 11, 16, and 18 at Month 72
Description	[Not Specified]
Time Frame	Month 72 (66 Months Post-dose 3 for the Original qHPV Vaccine Cohort and 36 months Post-dose 3 for the Extension Group)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 vaccinations within appropriate day ranges as defined in the CSR, were seronegative to the respective HPV type at Day 1 (for the Main Vaccination group), or Month 30 (for the Extension Group), and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study	qHPV Vaccine in Extension Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6	Represent participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36.
Overall Number of Participants Analyzed	550	276
Geometric Mean (95% Confidence Interval); Unit of Measure: milliMerck units/mL
Type 6: n=475, 151	118.9; (108.4 to 130.4)	113.9; (95.7 to 135.6)
Type 11: n=475, 151	135.7; (122.6 to 150.3)	137.9; (114.9 to 165.5)
Type 16: n=473, 154	521.2; (466.2 to 582.6)	485.8; (396.4 to 595.3)
Type 18: n=477, 160	70.9; (61.8 to 81.4)	67.7; (53.1 to 86.3)

6. Primary Outcome

Title	Geometric Mean Titers for Anti-HPV 6, 11, 16, and 18 at Month 96
Description	[Not Specified]
Time Frame	Month 96 (90 Months Post-dose 3 for Original qHPV Vaccine Group and 60 Months Post-dose 3 for Extension Group)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 vaccinations within appropriate day ranges as defined in the CSR, were seronegative to the respective HPV type at Day 1 (for the Main Vaccination group), or Month 30 (for the Extension Group), and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study	qHPV Vaccine in Extension Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6	Represent participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36.
Overall Number of Participants Analyzed	508	267
Geometric Mean (95% Confidence Interval); Unit of Measure: milliMerck units/mL
Type 6: n=451, 141	71.4; (64.6 to 79.0)	91.0; (76.4 to 108.6)
Type 11: n=451, 141	67.5; (60.1 to 75.7)	90.3; (74.0 to 110.1)
Type 16: n=447, 143	325.5; (288.6 to 367.1)	387.4; (314.7 to 476.9)
Type 18: n=452, 152	41.6; (36.5 to 47.5)	48.3; (37.6 to 62.0)

7. Primary Outcome

Title	Percentage of Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 96
Description	A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18.
Time Frame	Month 96 (90 Months Post-dose 3 for Original qHPV Vaccine Cohort and 60 Months Post-dose 3 for Extension Group)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations, were seronegative to the respective HPV type at Day 1 (for the Main Vaccination group), or Month 30 (for the Extension Group), and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study	qHPV Vaccine in Extension Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6	Represent participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36.
Overall Number of Participants Analyzed	508	267
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Type 6: n=451, 141	88.2; (84.9 to 91.1)	91.5; (85.6 to 95.5)
Type 11: n=451, 141	89.1; (85.9 to 91.9)	93.6; (88.2 to 97.0)
Type 16: n=447, 143	96.9; (94.8 to 98.3)	97.9; (94.0 to 99.6)
Type 18: n=452, 152	63.9; (59.3 to 68.4)	69.1; (61.1 to 76.3)

8. Primary Outcome

Title	Geometric Mean Titers for Anti-HPV 6, 11, 16, and 18 at Month 126
Description	[Not Specified]
Time Frame	Month 126 (120 Months Post-dose 3 for Original qHPV Vaccine Cohort and 90 Months Post-dose 3 for Extension Group)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 vaccinations within appropriate day ranges as defined in the CSR, were seronegative to the respective HPV type at Day 1 (for the Main Vaccination group), or Month 30 (for the Extension Group), and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study	qHPV Vaccine in Extension Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6	Represent participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36.
Overall Number of Participants Analyzed	454	211
Geometric Mean (95% Confidence Interval); Unit of Measure: milliMerck units/mL
Type 6: n=409, 112	88.0; (78.9 to 98.2)	99.3; (81.0 to 121.6)
Type 11: n=409, 112	74.6; (66.1 to 84.1)	96.0; (76.1 to 121.1)
Type 16: n=403, 115	320.1; (281.2 to 364.4)	351.6; (277.1 to 446.2)
Type 18: n=408, 120	36.5; (31.7 to 42.1)	39.6; (30.7 to 51.2)

9. Primary Outcome

Title	Percentage of Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 126
Description	A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18.
Time Frame	Month 126 (120 Months Post-dose 3 for Original qHPV Vaccine Cohort and 90 Months Post-dose 3 for Extension Group)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations, were seronegative to the respective HPV type at Day 1 (for the Main Vaccination group), or Month 30 (for the Extension Group), and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study	qHPV Vaccine in Extension Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6	Represent participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36.
Overall Number of Participants Analyzed	454	211
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Type 6: n=409, 112	89.0; (85.6 to 91.9)	91.1; (84.2 to 95.6)
Type 11: n=409, 112	88.8; (85.3 to 91.6)	92.9; (86.4 to 96.9)
Type 16: n=403, 115	96.0; (93.6 to 97.7)	96.5; (91.3 to 99.0)
Type 18: n=408, 120	60.5; (55.6 to 65.3)	65.0; (55.8 to 73.5)

10. Primary Outcome

Title	Number of Participants Reporting SAEs Related to Study Vaccine or to a Study Procedure in the Long-term Follow-up
Description	A serious adverse event is any adverse event that results in death, is life threatening, results in a persistent or significant disability/incapacity, results in hospitalization or prolongs an existing hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is considered an "other important medical event" based on medical judgment. SAEs considered by the investigator to be possibly, probably, or definitely related to study vaccine or a study procedure were reported.
Time Frame	Month 37 to Month 126

Outcome Measure Data

Analysis Population Description

The analysis population was all participants who were vaccinated according to actual treatment received and had safety follow-up.

Arm/Group Title	qHPV Vaccine in Base Study	qHPV Vaccine in Extension Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6	Represent participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36.
Overall Number of Participants Analyzed	821	424
Measure Type: Number; Unit of Measure: Participants
	0	1

11. Secondary Outcome

Title	Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 1 Postdose 3 (Month 7)
Description	A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18.
Time Frame	Month 7 (1 Month Postdose 3)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations, were seronegative to the respective HPV type at Day 1, and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6
Overall Number of Participants Analyzed	1082
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Type 6: n=953	99.8; (99.2 to 100)
Type 11: n=954	99.8; (99.2 to 100)
Type 16: n=949	99.7; (99.1 to 99.9)
Type 18: n=956	99.7; (99.1 to 99.9)

12. Secondary Outcome

Title	Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 12 Postdose 3 (Month 18).
Description	A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18.
Time Frame	Month 18 (12 Months Post-dose 3)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations, were seronegative to the respective HPV type at Day 1, and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6
Overall Number of Participants Analyzed	1106
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Type 6: n=937	97.8; (96.6 to 98.6)
Type 11: n=938	99.3; (98.5 to 99.7)
Type 16: n=933	99.6; (98.9 to 99.9)
Type 18: n=940	91.6; (89.6 to 93.3)

13. Secondary Outcome

Title	Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 18 Postdose 3 (Month 24)
Description	A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18.
Time Frame	Month 24 (18 Months Post-dose 3)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations, were seronegative to the respective HPV type at Day 1, and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6
Overall Number of Participants Analyzed	595
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Type 6: n=446	95.1; (92.6 to 96.9)
Type 11: n=447	98.2; (96.5 to 99.2)
Type 16: n=442	98.4; (96.8 to 99.4)
Type 18: n=447	87.5; (84.0 to 90.4)

14. Secondary Outcome

Title	Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 24 Postdose 3 (Month 30)
Description	A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18.
Time Frame	Month 30 (24 Months Post-dose 3)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations, were seronegative to the respective HPV type at Day 1, and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6
Overall Number of Participants Analyzed	911
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Type 6: n=799	95.6; (94.0 to 96.9)
Type 11: n=800	97.5; (96.2 to 98.5)
Type 16: n=795	98.6; (97.5 to 99.3)
Type 18: n=803	84.3; (81.6 to 86.8)

15. Secondary Outcome

Title	Percentage of Original qHPV Vaccine Participants Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 31 Postdose 3 (Month 37).
Description	A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18.
Time Frame	Month 37 (31 Months Post-dose 3)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations, were seronegative to the respective HPV type at Day 1, and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6
Overall Number of Participants Analyzed	772
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Type 6: n=657	94.5; (92.5 to 96.1)
Type 11: n=657	96.0; (94.3 to 97.4)
Type 16: n=655	98.2; (96.8 to 99.0)
Type 18: n=660	81.1; (77.9 to 84.0)

16. Secondary Outcome

Title	Percentage of Participants in the Extension Group Who Are Seropositive for HPV Types 6, 11, 16, and 18 at Month 1 Postdose 3 of qHPV (Month 37)
Description	A participant is considered seropositive for a given HPV type if he or she has a cLIA titer at or above the serostatus cutoff for that HPV type. Serostatus cutoffs are ≥ 20 mMU/mL for HPV 6 and 16, ≥ 16 mMU/mL for HPV 11, and ≥ 24 mMU/mL for HPV 18.
Time Frame	Month 37 (1 Month Post-dose 3 of qHPV)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations, were seronegative to the respective HPV type at Month 30, and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Extension Study
Arm/Group Description:	Represent participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36.
Overall Number of Participants Analyzed	440
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Type 6: n=246	99.6; (97.8 to 100)
Type 11: n=246	100; (98.5 to 100)
Type 16: n=246	100; (98.5 to 100)
Type 18: n=255	98.8; (96.6 to 99.8)

17. Secondary Outcome

Title	Geometric Mean Titers of Original qHPV Vaccine Cohort for Anti-HPV 6, 11, 16, and 18 at Month 1 Postdose 3 of qHPV Vaccine (Month 7)
Description	[Not Specified]
Time Frame	Month 7 (1 Month Post-dose 3)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations, were seronegative to the respective HPV type at Day 1, and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6
Overall Number of Participants Analyzed	1082
Geometric Mean (95% Confidence Interval); Unit of Measure: milliMerck units/mL
Type 6: n=953	929.2; (871.0 to 991.4)
Type 11: n=954	1362.8; (1279.8 to 1451.3)
Type 16: n=949	5512.7; (5109.9 to 5947.2)
Type 18: n=956	1278.9; (1183.2 to 1382.4)

18. Secondary Outcome

Title	Geometric Mean Titers of Original qHPV Vaccine Cohort for Anti-HPV 6, 11, 16, and 18 at Month 12 Postdose 3 of qHPV Vaccine (Month 18)
Description	[Not Specified]
Time Frame	Month 18 (Month 12 Post-dose 3)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations, were seronegative to the respective HPV type at Day 1, and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6
Overall Number of Participants Analyzed	1106
Geometric Mean (95% Confidence Interval); Unit of Measure: milliMerck units/mL
Type 6: n=937	219.3; (204.9 to 234.7)
Type 11: n=938	296.9; (276.9 to 318.3)
Type 16: n=933	1314.8; (1220.5 to 1416.5)
Type 18: n=940	203.0; (184.1 to 223.9)

19. Secondary Outcome

Title	Geometric Mean Titers of Original qHPV Vaccine Cohort for Anti-HPV 6, 11, 16, and 18 at Month 18 Postdose 3 of qHPV Vaccine (Month 24)
Description	[Not Specified]
Time Frame	Month 24 (18 Months Post-dose 3)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations, were seronegative to the respective HPV type at Day 1, and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study
Arm/Group Description:	Represent participants randomized to the qHPV vaccine group
Overall Number of Participants Analyzed	595
Geometric Mean (95% Confidence Interval); Unit of Measure: milliMerck units/mL
Type 6: n=446	143.5; (129.2 to 159.5)
Type 11: n=447	206.6; (186.9 to 228.3)
Type 16: n=442	932.1; (833.3 to 1042.7)
Type 18: n=447	136.2; (118.5 to 156.6)

20. Secondary Outcome

Title	Geometric Mean Titers of Original qHPV Vaccine Cohort for Anti-HPV 6, 11, 16, and 18 at Month 24 Postdose 3 of qHPV Vaccine (Month 30)
Description	[Not Specified]
Time Frame	Month 30 (24 Months Post-dose 3)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations, were seronegative to the respective HPV type at Day 1, and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6
Overall Number of Participants Analyzed	911
Geometric Mean (95% Confidence Interval); Unit of Measure: milliMerck units/mL
Type 6: n=799	146.5; (135.6 to 158.2)
Type 11: n=800	177.0; (163.6 to 191.5)
Type 16: n=795	826.1; (757.8 to 900.5)
Type 18: n=803	114.7; (102.8 to 127.9)

21. Secondary Outcome

Title	Geometric Mean Titers of Original qHPV Vaccine Cohort for Anti-HPV 6, 11, 16, and 18 at Month 31 Postdose 3 of qHPV Vaccine (Month 37)
Description	[Not Specified]
Time Frame	Month 37 (31 Months Post-dose 3)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations, were seronegative to the respective HPV type at Day 1, and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Base Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6
Overall Number of Participants Analyzed	772
Geometric Mean (95% Confidence Interval); Unit of Measure: milliMerck units/mL
Type 6: n=657	128.6; (118.2 to 139.9)
Type 11: n=657	149.7; (137.0 to 163.6)
Type 16: n=655	680.4; (617.2 to 750.1)
Type 18: n=660	102.4; (90.9 to 115.3)

22. Secondary Outcome

Title	Geometric Mean Titers in the Extension Group for Anti-HPV 6, 11, 16, and 18 at Month 1 Postdose 3 of qHPV Vaccine (Month 37)
Description	[Not Specified]
Time Frame	Month 37 (1 Month Post-dose 3 of qHPV)

Outcome Measure Data

Analysis Population Description

Per-protocol population: participants without protocol violations who received all 3 qHPV vaccinations within appropriate day ranges, were seronegative to the respective HPV type at Month 30, and had a valid serology result at the specified time for assessment.

Arm/Group Title	qHPV Vaccine in Extension Study
Arm/Group Description:	Represent participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36.
Overall Number of Participants Analyzed	440
Geometric Mean (95% Confidence Interval); Unit of Measure: milliMerck units/mL
Type 6: n=246	768.6; (676.6 to 873.0)
Type 11: n=246	1041.0; (919.8 to 1178.2)
Type 16: n=246	4312.7; (3715.6 to 5005.7)
Type 18: n=255	830.1; (714.0 to 965.1)

23. Secondary Outcome

Title	Combined Incidence of HPV 6/11/16/18-related Persistent Infection and HPV 6/11/16/18-related CIN, AIS, VIN, VaIN, Genital Warts, and Cervical/Vaginal/Vulvar Cancer in Females
Description	The HPV types were determined by polymerase chain reaction (PCR) testing. The combined incidence of HPV 6/11/16/18-related persistent infection and HPV 6/11/16/18-related cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), genital warts, and cervical/Vaginal/vulvar cancer was assessed in female participants.
Time Frame	Up to Month 126

Outcome Measure Data

Analysis Population Description

Per-Protocol Effectiveness population: male participants without protocol violations who received at least 1 dose of qHPV vaccine and at least 1 effectiveness follow-up visit.

Arm/Group Title	qHPV Vaccine in Base Study	qHPV Vaccine in Extension Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6	Represent participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36.
Overall Number of Participants Analyzed	259	96
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Cases per 100 person-years at risk
	0.2; (0.1 to 0.7)	0.2; (0.0 to 1.4)

24. Secondary Outcome

Title	Combined Incidence of HPV 6/11/16/18-related Persistent Infection and HPV 6/11/16/18-related PIN, Genital Warts, and Penile/Perineal/Perianal Cancer in Males
Description	The HPV types were determined by PCR testing. Combined incidence of HPV 6/11/16/18-related persistent infection and HPV 6/11/16/18-related penile/perineal/perianal intraepithelial neoplasia (PIN), genital warts, and penile/perineal/perianal cancer was assessed in male participants.
Time Frame	Up to Month 126

Outcome Measure Data

Analysis Population Description

Per-Protocol Effectiveness population: male participants without protocol violations who received at least 1 dose of qHPV vaccine and at least 1 effectiveness follow-up visit.

Arm/Group Title	qHPV Vaccine in Base Study	qHPV Vaccine in Extension Study
Arm/Group Description:	Represents participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of V501 (qHPV) at Day 1, Month 2, and Month 6	Represent participants originally enrolled into the Placebo Group who continued in the study to receive 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36.
Overall Number of Participants Analyzed	179	62
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Cases per 100 person-years at risk
	0.6; (0.2 to 1.5)	0.3; (0.0 to 1.9)

Adverse Events

Time Frame	Day 1 to Month 30 and Month 30 to Month 126
Adverse Event Reporting Description	Day 1 to Month 30: All adverse events were collected up to Day 15 after any vaccination. Month 30 to Month 126: Nonserious AEs were not collected. Deaths and related SAEs were collected throughout the study. Non-serious AEs were not solicited during the Extension Study; any reported non-serious AEs were unsolicited and not systematically assessed.
Arm/Group Title	qHPV Vaccine in Base: Vaccine Phase and Follow-up		Placebo in Base: Vaccine Phase and Follow-up		qHPV Vaccine in Base: Extension and Long-term Follow-up		qHPV Vaccine in Extension: Extension and Long-term Follow-up
Arm/Group Description	Participants who were randomized into the qHPV Group, who received three 0.5 mL intramuscular injections of qHPV at Day 1, Month 2, and Month 6, and had safety follow-up. Adverse events are reported for this group from Day 1 to Month 30.		Participants who were randomized into the Placebo Group, who received three 0.5 mL intramuscular injections of placebo vaccine at Day 1, Month 2, and Month 6, and had safety followup. Adverse events are reported for this group from Day 1 to Month 30.		Participants who received qHPV in the Base Study. No study treatment was administered after Month 6 for these participants. Adverse events are reported for this group from Month 30 to Month 126. Non-serious AEs were not solicited.		Participants who received placebo in the Base Study and three 0.5 mL intramuscular injections of V501 (qHPV) at Month 30, Month 32, and Month 36 in the Extension Study. Adverse events are reported for this group from Month 30 to Month 126. Non-serious AEs were not solicited.
All-Cause Mortality
	qHPV Vaccine in Base: Vaccine Phase and Follow-up		Placebo in Base: Vaccine Phase and Follow-up		qHPV Vaccine in Base: Extension and Long-term Follow-up		qHPV Vaccine in Extension: Extension and Long-term Follow-up
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--
Serious Adverse Events
	qHPV Vaccine in Base: Vaccine Phase and Follow-up		Placebo in Base: Vaccine Phase and Follow-up		qHPV Vaccine in Base: Extension and Long-term Follow-up		qHPV Vaccine in Extension: Extension and Long-term Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/1165 (0.52%)		0/584 (0.00%)		2/932 (0.21%)		3/481 (0.62%)
Blood and lymphatic system disorders
Haemorrhagic anaemia * 1	1/1165 (0.09%)	1	0/584 (0.00%)	0	0/932 (0.00%)	0	0/481 (0.00%)	0
Gastrointestinal disorders
Colitis ulcerative * 1	1/1165 (0.09%)	1	0/584 (0.00%)	0	0/932 (0.00%)	0	0/481 (0.00%)	0
General disorders
Chest pain * 1	0/1165 (0.00%)	0	0/584 (0.00%)	0	0/932 (0.00%)	0	1/481 (0.21%)	1
Infections and infestations
Appendicitis * 1	1/1165 (0.09%)	1	0/584 (0.00%)	0	0/932 (0.00%)	0	0/481 (0.00%)	0
Localised infection * 1	1/1165 (0.09%)	1	0/584 (0.00%)	0	0/932 (0.00%)	0	0/481 (0.00%)	0
Injury, poisoning and procedural complications
Meniscus injury * 1	0/1165 (0.00%)	0	0/584 (0.00%)	0	0/932 (0.00%)	0	1/481 (0.21%)	1
Road traffic accident * 1	0/1165 (0.00%)	0	0/584 (0.00%)	0	1/932 (0.11%)	1	0/481 (0.00%)	0
Metabolism and nutrition disorders
Type 1 diabetes mellitus * 1	1/1165 (0.09%)	1	0/584 (0.00%)	0	0/932 (0.00%)	0	0/481 (0.00%)	0
Musculoskeletal and connective tissue disorders
Pain in extremity * 1	1/1165 (0.09%)	1	0/584 (0.00%)	0	0/932 (0.00%)	0	0/481 (0.00%)	0
Nervous system disorders
VIIth nerve paralysis * 1	0/1165 (0.00%)	0	0/584 (0.00%)	0	0/932 (0.00%)	0	1/481 (0.21%)	1
Tonic clonic movements * 1	0/1165 (0.00%)	0	0/584 (0.00%)	0	1/932 (0.11%)	1	0/481 (0.00%)	0
Renal and urinary disorders
Acute kidney injury * 1	1/1165 (0.09%)	1	0/584 (0.00%)	0	0/932 (0.00%)	0	0/481 (0.00%)	0
Reproductive system and breast disorders
Dysfunctional uterine bleeding * 1	1/1165 (0.09%)	1	0/584 (0.00%)	0	0/932 (0.00%)	0	0/481 (0.00%)	0
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 11.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	4%
	qHPV Vaccine in Base: Vaccine Phase and Follow-up		Placebo in Base: Vaccine Phase and Follow-up		qHPV Vaccine in Base: Extension and Long-term Follow-up		qHPV Vaccine in Extension: Extension and Long-term Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	918/1165 (78.80%)		344/584 (58.90%)		0/932 (0.00%)		3/481 (0.62%)
General disorders
Injection site erythema * 1	237/1165 (20.34%)	323	78/584 (13.36%)	109	0/932 (0.00%)	0	1/481 (0.21%)	1
Injection site pain * 2	853/1165 (73.22%)	1705	268/584 (45.89%)	434	0/932 (0.00%)	0	3/481 (0.62%)	3
Injection site swelling * 2	241/1165 (20.69%)	336	45/584 (7.71%)	63	0/932 (0.00%)	0	1/481 (0.21%)	1
Pyrexia * 1	100/1165 (8.58%)	114	44/584 (7.53%)	60	0/932 (0.00%)	0	0/481 (0.00%)	0
Nervous system disorders
Headache * 1	221/1165 (18.97%)	297	111/584 (19.01%)	163	0/932 (0.00%)	0	0/481 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain * 1	52/1165 (4.46%)	56	24/584 (4.11%)	26	0/932 (0.00%)	0	0/481 (0.00%)	0
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 7.1; 2 Term from vocabulary, MedDRA 11.0

Limitations and Caveats

The difference between the prior and final data is a minor change in the definition of the per-protocol immunogenicity population, which was applied down to the base study. Also, protocol violators were identified and excluded from the analysis.

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.

Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

• Name/Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

Publications of Results:

Ferris D, Samakoses R, Block SL, Lazcano-Ponce E, Restrepo JA, Reisinger KS, Mehlsen J, Chatterjee A, Iversen OE, Sings HL, Shou Q, Sausser TA, Saah A. Long-term study of a quadrivalent human papillomavirus vaccine. Pediatrics. 2014 Sep;134(3):e657-65. doi: 10.1542/peds.2013-4144. Epub 2014 Aug 18.

Ferris DG, Samakoses R, Block SL, Lazcano-Ponce E, Restrepo JA, Mehlsen J, Chatterjee A, Iversen OE, Joshi A, Chu JL, Krick AL, Saah A, Das R. 4-Valent Human Papillomavirus (4vHPV) Vaccine in Preadolescents and Adolescents After 10 Years. Pediatrics. 2017 Dec;140(6). pii: e20163947. doi: 10.1542/peds.2016-3947.

Other Publications:

Reisinger KS, Block SL, Lazcano-Ponce E, Samakoses R, Esser MT, Erick J, Puchalski D, Giacoletti KE, Sings HL, Lukac S, Alvarez FB, Barr E. Safety and persistent immunogenicity of a quadrivalent human papillomavirus types 6, 11, 16, 18 L1 virus-like particle vaccine in preadolescents and adolescents: a randomized controlled trial. Pediatr Infect Dis J. 2007 Mar;26(3):201-9.

Perez G, Lazcano-Ponce E, Hernandez-Avila M, García PJ, Muñoz N, Villa LL, Bryan J, Taddeo FJ, Lu S, Esser MT, Vuocolo S, Sattler C, Barr E. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like-particle vaccine in Latin American women. Int J Cancer. 2008 Mar 15;122(6):1311-8.

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

Garland SM, Ault KA, Gall SA, Paavonen J, Sings HL, Ciprero KL, Saah A, Marino D, Ryan D, Radley D, Zhou H, Haupt RM, Garner EI; Quadrivalent Human Papillomavirus Vaccine Phase III Investigators. Pregnancy and infant outcomes in the clinical trials of a human papillomavirus type 6/11/16/18 vaccine: a combined analysis of five randomized controlled trials. Obstet Gynecol. 2009 Dec;114(6):1179-88. doi: 10.1097/AOG.0b013e3181c2ca21.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00092547
• Other Study ID Numbers: V501-018; 2004_084
• First Submitted: September 23, 2004
• First Posted: September 28, 2004
• Results First Submitted: November 3, 2009
• Results First Posted: May 4, 2010
• Last Update Posted: February 20, 2018