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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01651949
Recruitment Status : Completed
First Posted : July 27, 2012
Results First Posted : March 9, 2015
Last Update Posted : November 27, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions Genital Warts
Anal Cancer
Anal Intraepithelial Neoplasia
Intervention Biological: 9vHPV Vaccine
Enrollment 2520
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Heterosexual Males Females Men Who Have Sex With Men (MSM)
Hide Arm/Group Description Healthy heterosexual males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6 Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6 Healthy MSM 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Period Title: Overall Study
Started 1106 1101 313
Vaccination 1 1103 1099 313
Vaccination 2 1089 1069 298
Vaccination 3 1067 1037 291
Completed 1053 1015 282
Not Completed 53 86 31
Reason Not Completed
Unknown status             4             4             0
Lost to Follow-up             30             56             20
Protocol Violation             0             2             1
Physician Decision             0             2             0
Adverse Event             0             2             1
Screen failure             2             2             0
Withdrawal by Subject             17             18             9
Arm/Group Title Heterosexual Males Females Men Who Have Sex With Men (MSM) Total
Hide Arm/Group Description Healthy heterosexual males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6 Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6 Healthy MSM 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6 Total of all reporting groups
Overall Number of Baseline Participants 1106 1101 313 2520
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1106 participants 1101 participants 313 participants 2520 participants
20.8  (3.0) 21.3  (2.9) 22.2  (2.4) 21.2  (2.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1106 participants 1101 participants 313 participants 2520 participants
Female
0
   0.0%
1101
 100.0%
0
   0.0%
1101
  43.7%
Male
1106
 100.0%
0
   0.0%
313
 100.0%
1419
  56.3%
1.Primary Outcome
Title Geometric Mean Titers (GMTs) to the HPV Types Contained in the 9vHPV Vaccine
Hide Description Serum antibodies to HPV types 6/11/16/18/31/33/45/52/58 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL
Time Frame Four weeks post vaccination 3 (Month 7)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis set includes heterosexual male and female participants who received the 3 vaccinations, were seronegative to the appropriate HPV type at baseline, and had Month 7 immunogenicity results for the appropriate HPV type. Per-protocol non-inferiority analysis compared heterosexual males and females only.
Arm/Group Title Heterosexual Males Females Men Who Have Sex With Men
Hide Arm/Group Description:
Healthy heterosexual males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Healthy MSM 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Overall Number of Participants Analyzed 914 884 239
Geometric Mean (95% Confidence Interval)
Unit of Measure: milli Merck Units/mL
Anti-HPV Type 6 (n=847, 708, 164)
782.0
(738.0 to 828.7)
703.9
(660.6 to 749.9)
568.9
(498.7 to 649.0)
Anti-HPV Type 11 (n=851, 712, 165)
616.7
(582.4 to 653.0)
564.9
(530.6 to 601.3)
437.7
(384.4 to 498.5)
Anti-HPV Type 16 (n=899, 781, 212)
3346.0
(3158.9 to 3544.1)
2788.3
(2621.4 to 2965.8)
2294.0
(2037.8 to 2582.5)
Anti-HPV Type 18 (n=906, 831, 220)
808.2
(754.9 to 865.4)
679.8
(633.1 to 730.1)
608.1
(529.4 to 698.5)
Anti-HPV Type 31 (n=908, 826, 227)
708.5
(662.7 to 757.6)
570.1
(531.5 to 611.5)
420.7
(368.0 to 480.9)
Anti-HPV Type 33 (n=901, 853, 230)
384.8
(362.5 to 408.4)
322.0
(302.9 to 342.3)
252.3
(224.2 to 283.8)
Anti-HPV Type 45 (n=909, 871, 232)
235.6
(219.0 to 253.6)
185.7
(172.3 to 200.2)
157.5
(136.2 to 182.2)
Anti-HPV Type 52 (n=907, 849, 232)
386.8
(363.4 to 411.6)
335.2
(314.3 to 357.6)
233.1
(206.0 to 263.7)
Anti-HPV Type 58 (n=897, 839, 223)
509.8
(479.9 to 541.6)
409.3
(384.5 to 435.7)
319.8
(283.2 to 361.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 6
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to GMT ratio (heterosexual males / females) required that the lower bound of the 95% confidence interval was >0.67, to exclude a decrease of 1.5-fold or more
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments An analysis of variance model with a response of log individual titers and fixed effect for group was used.
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
1.02 to 1.21
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 11
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to GMT ratio (heterosexual males / females) required that the lower bound of the 95% confidence interval was >0.67, to exclude a decrease of 1.5-fold or more
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments An analysis of variance model with a response of log individual titers and fixed effect for group was used
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
1.00 to 1.19
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 16
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to GMT ratio (heterosexual males / females) required that the lower bound of the 95% confidence interval was >0.67, to exclude a decrease of 1.5-fold or more
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments An analysis of variance model with a response of log individual titers and fixed effect for group was used
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
1.10 to 1.30
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 18
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to GMT ratio (heterosexual males / females) required that the lower bound of the 95% confidence interval was >0.67, to exclude a decrease of 1.5-fold or more
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments An analysis of variance model with a response of log individual titers and fixed effect for group was used
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.19
Confidence Interval (2-Sided) 95%
1.08 to 1.31
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 31
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to GMT ratio (heterosexual males / females) required that the lower bound of the 95% confidence interval was >0.67, to exclude a decrease of 1.5-fold or more
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments An analysis of variance model with a response of log individual titers and fixed effect for group was used
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.24
Confidence Interval (2-Sided) 95%
1.13 to 1.37
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 33
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to GMT ratio (heterosexual males / females) required that the lower bound of the 95% confidence interval was >0.67, to exclude a decrease of 1.5-fold or more
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments An analysis of variance model with a response of log individual titers and fixed effect for group was used
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.19
Confidence Interval (2-Sided) 95%
1.10 to 1.30
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 45
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to GMT ratio (heterosexual males / females) required that the lower bound of the 95% confidence interval was >0.67, to exclude a decrease of 1.5-fold or more
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments An analysis of variance model with a response of log individual titers and fixed effect for group was used
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
1.14 to 1.41
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 52
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to GMT ratio (heterosexual males / females) required that the lower bound of the 95% confidence interval was >0.67, to exclude a decrease of 1.5-fold or more
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments An analysis of variance model with a response of log individual titers and fixed effect for group was used
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
1.05 to 1.26
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 58
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to GMT ratio (heterosexual males / females) required that the lower bound of the 95% confidence interval was >0.67, to exclude a decrease of 1.5-fold or more
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments An analysis of variance model with a response of log individual titers and fixed effect for group was used
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
1.14 to 1.36
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With One or More Injection-site Adverse Experiences Prompted on the Vaccination Report Card
Hide Description An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Injection-site AEs prompted on the Vaccination Report Card (VRC) were erythema, pain, and swelling. Participants were instructed to use the Vaccination Report Card to record AEs daily after each study vaccination.
Time Frame Up to 5 days after any vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis set includes all participants who received >=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Arm/Group Title Heterosexual and MSM Males Females
Hide Arm/Group Description:
Healthy heterosexual and MSM males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Overall Number of Participants Analyzed 1394 1075
Measure Type: Number
Unit of Measure: Percentage of Participants
Overall injection-site AEs 66.7 84.0
Injection-site Erythema 20.7 32.2
Injection-site Pain 63.4 82.5
Injection-site Swelling 20.2 37.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Heterosexual and MSM Males, Females
Comments Injection-site Erythema
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -11.5
Confidence Interval (2-Sided) 95%
-15.0 to -8.0
Estimation Comments The incidence of AEs of injection-site erythema reported on the Vaccination Report Card was compared between heterosexual / MSM male participants and female participants
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Heterosexual and MSM Males, Females
Comments Injection-site Pain
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -19.1
Confidence Interval (2-Sided) 95%
-22.5 to -15.7
Estimation Comments The incidence of AEs of injection-site erythema reported on the Vaccination Report Card was compared between heterosexual / MSM male participants and female participants
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Heterosexual and MSM Males, Females
Comments Injection-site Swelling
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -17.3
Confidence Interval (2-Sided) 95%
-20.8 to -13.7
Estimation Comments The incidence of AEs of injection-site erythema reported on the Vaccination Report Card was compared between heterosexual / MSM male participants and female participants
3.Primary Outcome
Title Percentage of Participants With Elevated Oral Body Temperature (>=37.8° C, >=100° F)
Hide Description Participants were instructed by the investigator to use the Vaccination Report Card to document evening oral temperature daily after each study vaccination
Time Frame Up to 5 days after any vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis set includes all participants who received >=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Arm/Group Title Heterosexual and MSM Males Females
Hide Arm/Group Description:
Healthy heterosexual and MSM males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Overall Number of Participants Analyzed 1386 1066
Measure Type: Number
Unit of Measure: Percentage of Participants
4.4 5.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Heterosexual and MSM Males, Females
Comments Elevated Body Temperature
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.091
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-3.4 to 0.2
Estimation Comments The incidence of maximum body temperature >=37.8° C reported on the Vaccination Report Card was compared between heterosexual / MSM male participants and female participants
4.Primary Outcome
Title Percentage of Participants With an Adverse Event
Hide Description An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE.
Time Frame Up to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis set includes all participants who received >=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Arm/Group Title Heterosexual and MSM Males Females
Hide Arm/Group Description:
Healthy heterosexual and MSM males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Overall Number of Participants Analyzed 1394 1075
Measure Type: Number
Unit of Measure: Percentage of Participants
76.2 89.4
5.Primary Outcome
Title Percentage of Participants Who Had Study Vaccine Discontinued Due to an Adverse Event
Hide Description An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE.
Time Frame Up to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis set includes all participants who received >=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
Arm/Group Title Heterosexual and MSM Males Females
Hide Arm/Group Description:
Healthy heterosexual and MSM males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Overall Number of Participants Analyzed 1394 1075
Measure Type: Number
Unit of Measure: Percentage of Participants
0.1 0.3
6.Secondary Outcome
Title Percentage of Participants With Seroconversion to the HPV Types Contained in the 9vHPV Vaccine
Hide Description Serum antibodies to HPV types were measured with a Competitive Luminex Immunoassay. The serostatus cutoffs (milli Merck U/mL) for HPV types were as follows: HPV Type 6: ≥30; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24; HPV Type 31: ≥10; HPV Types 33, 45, 52, and 58: ≥8.
Time Frame Four weeks post vaccination 3 (Month 7)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis set includes participants who received the 3 vaccinations, were seronegative to the appropriate HPV type at baseline, and had Month 7 immunogenicity results for the appropriate HPV type. Per-protocol non-inferiority analysis compared heterosexual males and females only.
Arm/Group Title Heterosexual Males Females Men Who Have Sex With Men
Hide Arm/Group Description:
Healthy heterosexual males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Healthy MSM 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
Overall Number of Participants Analyzed 914 884 239
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Anti-HPV Type 6 (n=847, 708, 164)
99.6
(99.0 to 99.9)
99.6
(98.8 to 99.9)
99.4
(96.6 to 100)
Anti-HPV Type 11 (n=851, 712, 165)
100
(99.6 to 100)
99.9
(99.2 to 100)
100
(97.8 to 100)
Anti-HPV Type 16 (n=899, 781, 212)
100
(99.6 to 100)
99.9
(99.3 to 100)
100
(98.3 to 100)
Anti-HPV Type 18 (n=906, 831, 220)
99.9
(99.4 to 100)
99.8
(99.1 to 100)
99.5
(97.5 to 100)
Anti-HPV Type 31 (n=908, 826, 227)
100
(99.6 to 100)
100
(99.6 to 100)
100
(98.4 to 100)
Anti-HPV Type 33 (n=901, 853, 230)
100
(99.6 to 100)
99.9
(99.3 to 100)
100
(98.4 to 100)
Anti-HPV Type 45 (n=909, 871, 232)
99.8
(99.2 to 100)
99.5
(98.8 to 99.9)
100
(98.4 to 100)
Anti-HPV Type 52 (n=907, 849, 232)
100
(99.6 to 100)
99.8
(99.2 to 100)
100
(98.4 to 100)
Anti-HPV Type 58 (n=897, 839, 223)
100
(99.6 to 100)
99.8
(99.1 to 100)
100
(98.4 to 100)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 6
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to seroconversion percentage (heterosexual males minus females) required that the lower bound of the 95% confidence interval was greater than -5
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.7 to 0.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 11
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to seroconversion percentage (heterosexual males minus females) required that the lower bound of the 95% confidence interval was greater than -5
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.8
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 16
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to seroconversion percentage (heterosexual males minus females) required that the lower bound of the 95% confidence interval was greater than -5
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 18
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to seroconversion percentage (heterosexual males minus females) required that the lower bound of the 95% confidence interval was greater than -5
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.4 to 0.8
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 31
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to seroconversion percentage (heterosexual males minus females) required that the lower bound of the 95% confidence interval was greater than -5
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.4 to 0.5
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 33
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to seroconversion percentage (heterosexual males minus females) required that the lower bound of the 95% confidence interval was greater than -5
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 45
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to seroconversion percentage (heterosexual males minus females) required that the lower bound of the 95% confidence interval was greater than -5
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.4 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 52
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to seroconversion percentage (heterosexual males minus females) required that the lower bound of the 95% confidence interval was greater than -5
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.2 to 0.9
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Heterosexual Males, Females
Comments Anti-HPV Type 58
Type of Statistical Test Non-Inferiority or Equivalence
Comments Criterion for non-inferiority with respect to seroconversion percentage (heterosexual males minus females) required that the lower bound of the 95% confidence interval was greater than -5
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Miettinen & Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.2 to 0.9
Estimation Comments [Not Specified]
Time Frame Up to Month 12
Adverse Event Reporting Description The analysis set includes all participants who received >=1 vaccination and had safety follow-up. Heterosexual and MSM males were combined for safety outcomes.
 
Arm/Group Title Heterosexual and MSM Males Females
Hide Arm/Group Description Healthy heterosexual and MSM males 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6 Healthy females 16 to 26 years of age received 9vHPV vaccine 0.5 mL intramuscular injection on Day 1, Month 1, and Month 6
All-Cause Mortality
Heterosexual and MSM Males Females
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Heterosexual and MSM Males Females
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/1394 (1.65%)      26/1075 (2.42%)    
Cardiac disorders     
Atrioventricular block second degree  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Congenital, familial and genetic disorders     
Familial periodic paralysis  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Gastrointestinal disorders     
Constipation  1  0/1394 (0.00%)  0 2/1075 (0.19%)  2
Vomiting  1  0/1394 (0.00%)  0 1/1075 (0.09%)  1
General disorders     
Cyst rupture  1  0/1394 (0.00%)  0 1/1075 (0.09%)  1
Device dislocation  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis  1  0/1394 (0.00%)  0 1/1075 (0.09%)  1
Infections and infestations     
Anal abscess  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Appendicitis  1  2/1394 (0.14%)  2 1/1075 (0.09%)  1
Appendicitis perforated  1  0/1394 (0.00%)  0 1/1075 (0.09%)  1
Dengue fever  1  0/1394 (0.00%)  0 1/1075 (0.09%)  1
Escherichia urinary tract infection  1  0/1394 (0.00%)  0 1/1075 (0.09%)  1
External ear cellulitis  1  0/1394 (0.00%)  0 1/1075 (0.09%)  1
Infectious mononucleosis  1  0/1394 (0.00%)  0 1/1075 (0.09%)  1
Pilonidal cyst  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Postoperative wound infection  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Pulmonary tuberculosis  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Viral infection  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Injury, poisoning and procedural complications     
Concussion  1  2/1394 (0.14%)  2 0/1075 (0.00%)  0
Exposure to communicable disease  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Radius fracture  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Tibia fracture  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Ligament disorder  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Nervous system disorders     
Cerebrovascular accident  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Migraine  1  1/1394 (0.07%)  1 1/1075 (0.09%)  1
Syncope  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Pregnancy, puerperium and perinatal conditions     
Abortion incomplete  1  0/1394 (0.00%)  0 1/1075 (0.09%)  1
Abortion spontaneous  1  0/1394 (0.00%)  0 4/1075 (0.37%)  4
Ectopic pregnancy  1  0/1394 (0.00%)  0 2/1075 (0.19%)  2
Foetal malpresentation  1  0/1394 (0.00%)  0 1/1075 (0.09%)  1
Psychiatric disorders     
Anxiety  1  0/1394 (0.00%)  0 1/1075 (0.09%)  1
Psychotic disorder  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Schizophreniform disorder  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Renal and urinary disorders     
Nephrolithiasis  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Renal failure acute  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Reproductive system and breast disorders     
Ovarian cyst  1  0/1394 (0.00%)  0 1/1075 (0.09%)  1
Ovarian cyst ruptured  1  0/1394 (0.00%)  0 1/1075 (0.09%)  1
Skin and subcutaneous tissue disorders     
Subcutaneous emphysema  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Surgical and medical procedures     
Abortion induced  1  0/1394 (0.00%)  0 4/1075 (0.37%)  4
Vascular disorders     
Haematoma  1  1/1394 (0.07%)  1 0/1075 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Heterosexual and MSM Males Females
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   976/1394 (70.01%)      924/1075 (85.95%)    
General disorders     
Injection site erythema  1  291/1394 (20.88%)  422 348/1075 (32.37%)  539
Injection site pain  1  886/1394 (63.56%)  1877 893/1075 (83.07%)  2101
Injection site swelling  1  285/1394 (20.44%)  431 408/1075 (37.95%)  661
Nervous system disorders     
Headache  1  200/1394 (14.35%)  271 246/1075 (22.88%)  378
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
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: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01651949     History of Changes
Other Study ID Numbers: V503-003
2012-002758-22 ( EudraCT Number )
First Submitted: July 25, 2012
First Posted: July 27, 2012
Results First Submitted: February 24, 2015
Results First Posted: March 9, 2015
Last Update Posted: November 27, 2018