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A Study of V503 (A Multivalent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] Vaccine) in Preadolescents and Adolescents (V503-002)

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: NCT00943722
Recruitment Status : Completed
First Posted : July 22, 2009
Results First Posted : January 13, 2015
Last Update Posted : October 3, 2022
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions Cervical Cancers
Vulvar Cancer
Vaginal Cancer
Genital Lesions
PAP Test Abnormalities
HPV Infections
Intervention Biological: V503
Enrollment 3074
Recruitment Details The base study was a 12-month study that collected immunogenicity data through Month 7 and safety data through Month 12.
Pre-assignment Details

Extension study 1 (EXT1) collected data to Month 36. Extension study 2 (EXT2) collected long-term data through ~Month 126. No study vaccine was administered.

Per protocol, participants enrolled in the 16- to 26-year-old arm in the base study were not included in the extension study.

Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered (arm: "Extension Study: 9- to 15- Year Old Females").

Arm/Group Title Base Study: 9- to 15-Year-Old Females (Lot 1) Base Study: 9- to 15-Year-Old Females (Lot 2) Base Study: 9- to 15-Year-Old Females (Lot 3) Base Study: 9- to 15-Year-Old Males (Lot 1) Base Study: 16- to 26-Year-Old Females (Lot 1) Extension Study: 9- to 15-Year-Old Females Extension Study: 9- to 15-Year-Old Males
Hide Arm/Group Description 9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1. 9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 2. 9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 3. 9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1. 9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1. In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2). In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2)
Period Title: Base Study
Started 648 643 644 669 470 0 0
Vaccination 1 646 642 644 666 468 0 0
Vaccination 2 637 633 638 658 462 0 0
Vaccination 3 635 627 637 653 455 0 0
At Least One Dose With Protocol-specified Safety Follow-up 643 639 641 662 466 0 0
Completed 623 621 631 647 444 0 0
Not Completed 25 22 13 22 26 0 0
Reason Not Completed
Adverse Event             0             0             0             1             0             0             0
Lost to Follow-up             12             8             10             8             11             0             0
Physician Decision             1             0             0             0             1             0             0
Pregnancy             0             0             1             0             2             0             0
Protocol Violation             0             1             0             0             2             0             0
Withdrawal by Subject             12             13             2             13             8             0             0
Month 12 visit not completed             0             0             0             0             2             0             0
Period Title: First Extension Study: EXT 1
Started [1] 0 0 0 0 0 1604 568
Completed 0 0 0 0 0 1489 527
Not Completed 0 0 0 0 0 115 41
Reason Not Completed
Adverse Event             0             0             0             0             0             1             0
Lost to Follow-up             0             0             0             0             0             38             10
Withdrawal by Subject             0             0             0             0             0             32             10
Disposition Unknown             0             0             0             0             0             44             21
[1]
The optional EXT1 included eligible participants from the base study, with the exception of 16-26 year old females.
Period Title: Second Extension Study: EXT 2
Started [1] 0 0 0 0 0 971 301
Completed 0 0 0 0 0 720 202
Not Completed 0 0 0 0 0 251 99
Reason Not Completed
Adverse Event             0             0             0             0             0             1             0
Lost to Follow-up             0             0             0             0             0             111             46
Physician Decision             0             0             0             0             0             1             3
Pregnancy             0             0             0             0             0             1             0
Withdrawal by Subject             0             0             0             0             0             137             50
[1]
The optional EXT2 included eligible participants from the base study, with the exception of 16-26 year old females.
Arm/Group Title Base Study: 9- to 15-Year-Old Females (Lot 1) Base Study: 9- to 15-Year-Old Females (Lot 2) Base Study: 9- to 15-Year-Old Females (Lot 3) Base Study: 9- to 15-Year-Old Males (Lot 1) Base Study: 16- to 26-Year-Old Females (Lot 1) Total
Hide Arm/Group Description 9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1. 9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 2. 9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 3. 9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1. 9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1. Total of all reporting groups
Overall Number of Baseline Participants 648 643 644 669 470 3074
Hide Baseline Analysis Population Description
Per protocol, baseline characteristics were analyzed in all participants randomized in the base study.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 648 participants 643 participants 644 participants 669 participants 470 participants 3074 participants
9 to 12 years 440 432 432 450 0 1754
13 to 15 years 208 211 212 219 0 850
16 to 26 years 0 0 0 0 470 470
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 648 participants 643 participants 644 participants 669 participants 470 participants 3074 participants
Female
648
 100.0%
643
 100.0%
644
 100.0%
0
   0.0%
470
 100.0%
2405
  78.2%
Male
0
   0.0%
0
   0.0%
0
   0.0%
669
 100.0%
0
   0.0%
669
  21.8%
1.Primary Outcome
Title Base Study: Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Females [Lot 1] and 16- to 26-Year-Old Females [Lot 1])
Hide Description Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using a competitive luminex immunoassay (cLIA). Titers were reported in milli Merck Units/mL.
Time Frame 4 weeks post-vaccination 3 (Month 7)
Hide Outcome Measure Data
Hide Analysis Population Description
9-15-year-old females and 16-26-year-old females who received 3 vaccinations from Lot 1 and met following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range.
Arm/Group Title Base Study: 9- to 15-Year-Old Females (Lot 1) Base Study: 9- to 15-Year-Old Males (Lot 1)
Hide Arm/Group Description:
9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed 535 378
Geometric Mean (95% Confidence Interval)
Unit of Measure: milli Merck Units/mL
Anti-HPV 6 Number Analyzed 517 participants 328 participants
1715.4
(1595.1 to 1844.7)
900.8
(822.3 to 986.9)
Anti-HPV 11 Number Analyzed 517 participants 332 participants
1295.1
(1204.1 to 1393.0)
706.6
(645.2 to 773.8)
Anti-HPV 16 Number Analyzed 529 participants 329 participants
6979.8
(6508.1 to 7485.8)
3522.6
(3223.5 to 3849.5)
Anti-HPV 18 Number Analyzed 531 participants 345 participants
2153.7
(1980.4 to 2342.1)
882.7
(795.4 to 979.5)
Anti-HPV 31 Number Analyzed 522 participants 340 participants
1891.6
(1745.7 to 2049.7)
753.9
(682.5 to 832.7)
Anti-HPV 33 Number Analyzed 534 participants 354 participants
980.4
(911.7 to 1054.3)
466.8
(426.9 to 510.3)
Anti-HPV 45 Number Analyzed 534 participants 368 participants
714.4
(651.9 to 782.8)
272.2
(243.8 to 303.9)
Anti-HPV 52 Number Analyzed 533 participants 337 participants
932.9
(864.8 to 1006.4)
419.6
(381.4 to 461.5)
Anti-HPV 58 Number Analyzed 531 participants 332 participants
1286.7
(1195.7 to 1384.6)
590.5
(538.2 to 647.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 6
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% confidence interval (CI) of GMT ratio be greater than 0.67.
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.90
Confidence Interval (2-Sided) 95%
1.70 to 2.14
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 11
Type of Statistical Test Non-Inferiority
Comments Non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.83
Confidence Interval (2-Sided) 95%
1.63 to 2.06
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 16
Type of Statistical Test Non-Inferiority
Comments Non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.98
Confidence Interval (2-Sided) 95%
1.77 to 2.22
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 18
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 2.44
Confidence Interval (2-Sided) 95%
2.13 to 2.80
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 31
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 2.51
Confidence Interval (2-Sided) 95%
2.21 to 2.85
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 33
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 2.10
Confidence Interval (2-Sided) 95%
1.87 to 2.36
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 45
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 2.62
Confidence Interval (2-Sided) 95%
2.27 to 3.03
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 52
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 2.22
Confidence Interval (2-Sided) 95%
1.97 to 2.51
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 58
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 2.18
Confidence Interval (2-Sided) 95%
1.93 to 2.45
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
2.Primary Outcome
Title Base Study: GMTs for Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Males [Lot 1] and 16- to 26-Year-Old Females [Lot 1])
Hide Description Serum antibody titers for HPV VLPs, Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using a competitive luminex immunoassay (cLIA). Titers were reported in milli Merck Units/mL.
Time Frame 4 weeks post-vaccination 3 (Month 7)
Hide Outcome Measure Data
Hide Analysis Population Description
9-15-year-old males and 16-26-year-old females who received 3 vaccinations from Lot 1 and met following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range.
Arm/Group Title Base Study: 9- to 15-Year-Old Males (Lot 1) Base Study: 16- to 26-Year-Old Females (Lot 1)
Hide Arm/Group Description:
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed 570 378
Geometric Mean (95% Confidence Interval)
Unit of Measure: milli Merck Units/mL
Anti-HPV 6 Number Analyzed 559 participants 328 participants
2084.7
(1944.0 to 2235.7)
900.8
(822.3 to 986.9)
Anti-HPV 11 Number Analyzed 559 participants 332 participants
1487.1
(1386.5 to 1595.0)
706.6
(645.2 to 773.8)
Anti-HPV 16 Number Analyzed 569 participants 329 participants
8628.9
(8065.9 to 9231.3)
3522.6
(3223.5 to 3849.5)
Anti-HPV 18 Number Analyzed 567 participants 345 participants
2822.8
(2602.8 to 3061.5)
882.7
(795.4 to 979.5)
Anti-HPV 31 Number Analyzed 564 participants 340 participants
2221.2
(2056.1 to 2399.5)
753.9
(682.5 to 832.7)
Anti-HPV 33 Number Analyzed 567 participants 354 participants
1198.7
(1117.1 to 1286.2)
466.8
(426.9 to 510.3)
Anti-HPV 45 Number Analyzed 570 participants 368 participants
907.0
(830.2 to 991.0)
272.2
(243.8 to 303.9)
Anti-HPV 52 Number Analyzed 568 participants 337 participants
1037.8
(964.4 to 1116.9)
419.6
(381.4 to 461.5)
Anti-HPV 58 Number Analyzed 566 participants 332 participants
1567.7
(1460.2 to 1683.1)
590.5
(538.2 to 647.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 6
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 2.31
Confidence Interval (2-Sided) 95%
2.07 to 2.59
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 11
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 2.10
Confidence Interval (2-Sided) 95%
1.88 to 2.36
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 16
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 2.45
Confidence Interval (2-Sided) 95%
2.19 to 2.74
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 18
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 3.20
Confidence Interval (2-Sided) 95%
2.80 to 3.65
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 31
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 2.95
Confidence Interval (2-Sided) 95%
2.60 to 3.34
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 33
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 2.57
Confidence Interval (2-Sided) 95%
2.29 to 2.88
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 45
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 3.33
Confidence Interval (2-Sided) 95%
2.89 to 3.84
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 52
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 2.47
Confidence Interval (2-Sided) 95%
2.19 to 2.79
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 58
Type of Statistical Test Non-Inferiority
Comments non-inferiority requires that the lower bound of two-sided 95% CI of GMT ratio be greater than 0.67
Statistical Test of Hypothesis P-Value < 0.001
Comments one-sided tests of non-inferiority conducted at the alpha=0.025 level; model with a response of log individual titers and a fixed effect for comparison group
Method ANOVA
Comments model with a response of log individual titers and a fixed effect for comparison group
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 2.66
Confidence Interval (2-Sided) 95%
2.37 to 2.98
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Males (Lot 1) divided by GMT for 16- to 26-Year-Old Females (Lot 1)
3.Primary Outcome
Title Base Study: GMTs for Each of the HPV Types Contained in the Vaccine (Lot Consistency Study)
Hide Description Serum antibody titers for HPV VLPs, Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using cLIA. Titers were reported in milli Merck Units/mL.
Time Frame 4 weeks post-vaccination 3 (Month 7)
Hide Outcome Measure Data
Hide Analysis Population Description
9-15-year-old females who received 3 vaccinations from Lots 1, 2, or 3 and met following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range.
Arm/Group Title Base Study: 9- to 15-Year-Old Females (Lot 1) Base Study: 9- to 15-Year-Old Females (Lot 2) Base Study: 9- to 15-Year-Old Females (Lot 3)
Hide Arm/Group Description:
9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 2.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 3.
Overall Number of Participants Analyzed 535 549 565
Geometric Mean (95% Confidence Interval)
Unit of Measure: milli Merck Units/mL
Anti-HPV 6 Number Analyzed 517 participants 536 participants 544 participants
1715.4
(1588.7 to 1852.2)
1763.3
(1635.4 to 1901.3)
1659.9
(1540.3 to 1788.7)
Anti-HPV 11 Number Analyzed 517 participants 536 participants 544 participants
1295.1
(1197.8 to 1400.3)
1311.7
(1214.9 to 1416.3)
1232.0
(1141.7 to 1329.5)
Anti-HPV 16 Number Analyzed 529 participants 542 participants 556 participants
6979.8
(6476.1 to 7522.8)
7292.9
(6772.7 to 7853.1)
6948.2
(6458.7 to 7474.9)
Anti-HPV 18 Number Analyzed 531 participants 547 participants 563 participants
2153.7
(1970.9 to 2353.5)
2134.1
(1955.6 to 2329.0)
1966.6
(1804.3 to 2143.5)
Anti-HPV 31 Number Analyzed 522 participants 542 participants 553 participants
1891.6
(1738.5 to 2058.2)
1867.8
(1719.3 to 2029.1)
1879.0
(1731.0 to 2039.6)
Anti-HPV 33 Number Analyzed 534 participants 543 participants 560 participants
980.4
(909.2 to 1057.2)
922.7
(856.2 to 994.4)
931.1
(865.0 to 1002.3)
Anti-HPV 45 Number Analyzed 534 participants 548 participants 565 participants
714.4
(650.1 to 785.0)
827.7
(754.1 to 908.5)
678.4
(619.0 to 743.6)
Anti-HPV 52 Number Analyzed 533 participants 547 participants 562 participants
932.9
(860.8 to 1011.0)
1007.9
(931.0 to 1091.2)
971.2
(898.1 to 1050.3)
Anti-HPV 58 Number Analyzed 531 participants 539 participants 560 participants
1286.7
(1190.0 to 1391.3)
1344.9
(1244.6 to 1453.3)
1208.1
(1119.6 to 1303.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 6
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.88 to 1.08
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 6
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0).
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.93 to 1.16
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 6
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0).
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.95 to 1.19
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 11
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0).
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.90 to 1.11
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 11
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0).
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.95 to 1.20
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 11
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0).
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.95 to 1.20
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 16
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0).
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.86 to 1.06
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 16
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.90 to 1.12
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 16
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.94 to 1.17
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 18
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.89 to 1.14
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 18
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.98 to 1.26
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 18
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.97 to 1.26
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 31
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.89 to 1.13
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 31
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.91 to 1.16
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 31
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.90 to 1.15
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 33
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.94 to 1.16
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 33
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.94 to 1.17
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 33
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.90 to 1.12
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 45
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.73 to 0.95
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 45
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.91 to 1.18
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 45
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.24
Confidence Interval (2-Sided) 95%
1.08 to 1.42
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 52
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.83 to 1.03
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 52
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.85 to 1.07
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 52
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.92 to 1.16
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 58
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.86 to 1.06
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 58
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.96 to 1.20
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 1) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 58
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the ratio of the GMTs be entirely contained within the interval (0.5, 2.0)
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
1.00 to 1.26
Estimation Comments GMT ratio = GMT for 9- to 15-Year-Old Females (Lot 2) divided by GMT for 9- to 15-Year-Old Females (Lot 3)
4.Primary Outcome
Title Base Study: Percentage of Participants With Injection Site Adverse Experiences (AEs)
Hide Description An AE was 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 vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine was also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site were recorded.
Time Frame Up to 5 days after any vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of 9vHPV vaccine and had available follow-up data. Per protocol, this outcome measure included data from 9- to 15-year-old females regardless of lot administered.
Arm/Group Title 9- to 15-Year-Old Females (Lots 1, 2 or 3) Base Study: 9- to 15-Year-Old Males (Lot 1) Base Study: 16- to 26-Year-Old Females (Lot 1)
Hide Arm/Group Description:
9-valent human papillomavirus (9vHPV) L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered is obtained from manufacturing Lots 1, 2, or 3.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed 1923 662 466
Measure Type: Number
Unit of Measure: Percentage of Participants
81.9 72.8 85.4
5.Primary Outcome
Title Base Study: Percentage of Participants With Systemic AEs
Hide Description An AE was 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 vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine was also an AE. Systemic AEs were those not categorized as injection-site AEs.
Time Frame Up to 15 days after any vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of 9vHPV vaccine and had available follow-up data. Per protocol, this outcome measure included data from 9- to 15-year-old females regardless of lot administered.
Arm/Group Title 9- to 15-Year-Old Females (Lots 1, 2 or 3) Base Study: 9- to 15-Year-Old Males (Lot 1) Base Study: 16- to 26-Year-Old Females (Lot 1)
Hide Arm/Group Description:
9-valent human papillomavirus (9vHPV) L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered is obtained from manufacturing Lots 1, 2, or 3.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed 1923 662 466
Measure Type: Number
Unit of Measure: Percentage of Participants
45.0 41.8 57.1
6.Primary Outcome
Title Base Study: Percentage of Participants With Body Temperature ≥100.0°F (≥37.8ºC)
Hide Description Participants collected their oral body temperature in the evening of their vaccination day and at the same time each day thereafter for 4 days. The maximum body temperature obtained within 5 days of any of the 3 vaccinations was recorded. The percentage of participants who had at least 1 oral body temperature reading that was ≥100.0°F (≥37.8ºC) was summarized.
Time Frame Up to 5 days after any vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of 9vHPV vaccine and had available follow-up data. Per protocol, this outcome measure included data from 9- to 15-year-old females regardless of lot administered.
Arm/Group Title 9- to 15-Year-Old Females (Lots 1, 2, or 3) Base Study: 9- to 15-Year-Old Males (Lot 1) Base Study: 16- to 26-Year-Old Females (Lot 1)
Hide Arm/Group Description:
Multivalent HPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered is obtained from manufacturing Lots 1, 2, or 3.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed 1908 660 463
Measure Type: Number
Unit of Measure: Percentage of Participants
8.4 10.0 8.4
7.Primary Outcome
Title Extension Study: GMTs For Each of the HPV Types Contained in the Vaccine
Hide Description Serum antibody titers (milli Merck Units/mL) measured by cLIA to each of the 9vHPV types were assessed. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.
Time Frame Up to ~Month 126
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who met the following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range.
Arm/Group Title Extension Study: 9- to 15-Year-Old Females Extension Study: 9- to 15-Year-Old Males
Hide Arm/Group Description:
In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).
In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2)
Overall Number of Participants Analyzed 971 301
Geometric Mean (95% Confidence Interval)
Unit of Measure: milli Merck Units/mL
Anti-HPV 6 Number Analyzed 341 participants 176 participants
122.3
(111.1 to 134.7)
129.5
(112.5 to 149.1)
Anti-HPV 11 Number Analyzed 332 participants 169 participants
80.2
(72.5 to 88.8)
91.0
(78.4 to 105.6)
Anti-HPV 16 Number Analyzed 388 participants 173 participants
403.0
(357.3 to 454.5)
414.3
(353.8 to 485.3)
Anti-HPV 18 Number Analyzed 347 participants 178 participants
128.1
(116.7 to 140.7)
148.4
(130.2 to 169.2)
Anti-HPV 31 Number Analyzed 343 participants 177 participants
108.9
(97.6 to 121.6)
128.6
(111.2 to 148.8)
Anti-HPV 33 Number Analyzed 344 participants 178 participants
59.2
(53.7 to 65.2)
69.6
(60.7 to 79.7)
Anti-HPV 45 Number Analyzed 325 participants 169 participants
42.1
(37.7 to 47.1)
49.8
(43.0 to 57.8)
Anti-HPV 52 Number Analyzed 348 participants 176 participants
55.3
(50.5 to 60.6)
59.6
(52.0 to 68.4)
Anti-HPV 58 Number Analyzed 342 participants 175 participants
76.5
(69.2 to 84.6)
90.5
(78.4 to 104.6)
8.Primary Outcome
Title Extension Study: Percentage of Participants Who Are Seropositive to Each of the HPV Types Contained in the Vaccine
Hide Description Serum antibody titers for HPV VLPs Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 was determined and reported in milli Merck Units/mL. The percentage of participants seropositive to each HPV type was reported. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.
Time Frame Up to ~Month 126
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who met the following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range.
Arm/Group Title Extension Study: 9- to 15-Year-Old Females Extension Study: 9- to 15-Year-Old Males
Hide Arm/Group Description:
In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).
In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2)
Overall Number of Participants Analyzed 971 301
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Anti-HPV 6 Number Analyzed 341 participants 176 participants
82.7
(78.3 to 86.6)
84.1
(77.8 to 89.2)
Anti-HPV 11 Number Analyzed 332 participants 169 participants
85.2
(81.0 to 88.9)
87.0
(81.0 to 91.7)
Anti-HPV 16 Number Analyzed 338 participants 173 participants
97.3
(95.0 to 98.8)
98.3
(95.0 to 99.6)
Anti-HPV 18 Number Analyzed 347 participants 178 participants
80.1
(75.5 to 84.2)
83.7
(77.4 to 88.8)
Anti-HPV 31 Number Analyzed 343 participants 177 participants
90.1
(86.4 to 93.0)
92.7
(87.8 to 96.0)
Anti-HPV 33 Number Analyzed 344 participants 178 participants
85.2
(81.0 to 88.8)
89.3
(83.8 to 93.4)
Anti-HPV 45 Number Analyzed 325 participants 169 participants
81.8
(77.2 to 85.9)
92.3
(87.2 to 95.8)
Anti-HPV 52 Number Analyzed 348 participants 176 participants
88.2
(84.4 to 91.4)
89.2
(83.7 to 93.4)
Anti-HPV 58 Number Analyzed 342 participants 175 participants
96.5
(94.0 to 98.2)
97.1
(93.5 to 99.1)
9.Secondary Outcome
Title Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Females [Lot 1] and 16- to 26-Year-Old Females [Lot 1])
Hide Description Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using cLIA. 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 Type 33: ≥8, HPV Type 45: ≥8, HPV Type 52: ≥8, and HPV Type 58: ≥8.
Time Frame 4 weeks post-vaccination 3 (Month 7)
Hide Outcome Measure Data
Hide Analysis Population Description
9-15-year-old females and 16-26-year-old females who received 3 vaccinations from Lot 1 and met following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range.
Arm/Group Title Base Study: 9- to 15-Year-Old Females (Lot 1) Base Study: 9- to 15-Year-Old Males (Lot 1)
Hide Arm/Group Description:
9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed 535 378
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Anti-HPV 6 cLIA ≥30 mMU/mL Number Analyzed 517 participants 328 participants
99.8
(98.9 to 100)
99.7
(98.3 to 100)
Anti-HPV 11 cLIA ≥16 mMU/mL Number Analyzed 517 participants 332 participants
100
(99.3 to 100.0)
100
(98.9 to 100.0)
Anti-HPV 16 cLIA ≥20 mMU/mL Number Analyzed 529 participants 329 participants
100
(99.3 to 100.0)
100
(98.9 to 100.0)
Anti-HPV 18 cLIA ≥24 mMU/mL Number Analyzed 531 participants 345 participants
99.8
(99.0 to 100.0)
99.7
(98.4 to 100.0)
Anti-HPV 31 cLIA ≥10 mMU/mL Number Analyzed 522 participants 340 participants
100.0
(99.3 to 100.0)
99.7
(98.4 to 100.0)
Anti-HPV 33 cLIA ≥8 mMU/mL Number Analyzed 534 participants 354 participants
100.0
(99.3 to 100.0)
99.7
(98.4 to 100.0)
Anti-HPV 45 cLIA ≥8 mMU/mL Number Analyzed 534 participants 368 participants
99.8
(99.0 to 100.0)
99.5
(98.1 to 99.9)
Anti-HPV 52 cLIA ≥8 mMU/mL Number Analyzed 533 participants 337 participants
100.0
(99.3 to 100.0)
99.7
(98.4 to 100.0)
Anti-HPV 58 cLIA ≥8 mMU/mL Number Analyzed 531 participants 332 participants
100.0
(99.3 to 100.0)
100.0
(98.9 to 100.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 6
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.8 to 1.5
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 11
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 1.2
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 16
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 1.2
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 18
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.8 to 1.5
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 31
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.7
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 33
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.6
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 45
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.6 to 1.8
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 52
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.7
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Males (Lot 1)
Comments Anti-HPV 58
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 1.2
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
10.Secondary Outcome
Title Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Males [Lot 1] Versus 16- to 26-Year-Old Females [Lot 1])
Hide Description Serum antibody titers for HPV VLPs, Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using cLIA. 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 Type 33: ≥8, HPV Type 45: ≥8, HPV Type 52: ≥8, and HPV Type 58: ≥8.
Time Frame 4 weeks post-vaccination 3 (Month 7)
Hide Outcome Measure Data
Hide Analysis Population Description
9-15-year-old males and 16-26-year-old females who received 3 vaccinations from Lot 1 and met following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range
Arm/Group Title Base Study: 9- to 15-Year-Old Males (Lot 1) Base Study: 16- to 26-Year-Old Females (Lot 1)
Hide Arm/Group Description:
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
Overall Number of Participants Analyzed 570 378
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Anti-HPV 6 cLIA ≥30 mMU/mL Number Analyzed 559 participants 328 participants
99.8
(99.0 to 100.0)
99.7
(98.3 to 100.0)
Anti-HPV 11 cLIA ≥16 mMU/mL Number Analyzed 559 participants 332 participants
100.0
(99.3 to 100.0)
100.0
(98.9 to 100.0)
Anti-HPV 16 cLIA ≥20 mMU/mL Number Analyzed 569 participants 329 participants
100.0
(99.4 to 100.0)
100.0
(98.9 to 100.0)
Anti-HPV 18 cLIA ≥24 mMU/mL Number Analyzed 567 participants 345 participants
100.0
(99.4 to 100.0)
99.7
(98.4 to 100.0)
Anti-HPV 31 cLIA ≥10 mMU/mL Number Analyzed 564 participants 340 participants
100.0
(99.3 to 100.0)
99.7
(98.4 to 100.0)
Anti-HPV 33 cLIA ≥8 mMU/mL Number Analyzed 567 participants 354 participants
100.0
(99.4 to 100.0)
99.7
(98.4 to 100.0)
Anti-HPV 45 cLIA ≥8 mMU/mL Number Analyzed 570 participants 368 participants
100.0
(99.4 to 100.0)
99.5
(98.1 to 99.9)
Anti-HPV 52 cLIA ≥8 mMU/mL Number Analyzed 568 participants 337 participants
100.0
(99.4 to 100.0)
99.7
(98.4 to 100.0)
Anti-HPV 58 cLIA ≥8 mMU/mL Number Analyzed 566 participants 332 participants
100.0
(99.4 to 100.0)
100.0
(98.9 to 100.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 6
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.7 to 1.5
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 11
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 1.2
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 16
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 1.2
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 18
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.6
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 31
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.7
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 33
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.6
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 45
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-0.1 to 2.0
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 52
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.7
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Males (Lot 1), Base Study: 16- to 26-Year-Old Females (Lot 1)
Comments Anti-HPV 58
Type of Statistical Test Non-Inferiority
Comments Noninferiority is demonstrated if the lower limit of the 95% CI for the percentage point difference is greater than -5.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Miettinen and Nurminen
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 1.2
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Males (Lot 1) minus 16- to 26-Year-Old Females (Lot 1)
11.Secondary Outcome
Title Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (Lot Consistency Study)
Hide Description Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post- vaccination 3 using cLIA. 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 Type 33: ≥8, HPV Type 45: ≥8, HPV Type 52: ≥8, and HPV Type 58: ≥8.
Time Frame 4 weeks post-vaccination 3 (Month 7)
Hide Outcome Measure Data
Hide Analysis Population Description
9- to 15-year-old females who received 3 vaccinations from Lots 1, 2, and 3 and met following criteria for at least 1 of the 9 HPV types: no general protocol violations, received all 3 vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range
Arm/Group Title Base Study: 9- to 15-Year-Old Females (Lot 1) Base Study: 9- to 15-Year-Old Females (Lot 2) Base Study: 9- to 15-Year-Old Females (Lot 3)
Hide Arm/Group Description:
9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 2.
9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 3.
Overall Number of Participants Analyzed 535 549 565
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
HPV 6 cLIA ≥30 mMU/mL Number Analyzed 517 participants 536 participants 544 participants
99.8
(98.9 to 100.0)
99.8
(99.0 to 100.0)
99.3
(98.1 to 99.8)
HPV 11 cLIA ≥16 mMU/mL Number Analyzed 517 participants 536 participants 544 participants
100.0
(99.3 to 100.0)
100.0
(99.3 to 100.0)
99.6
(98.7 to 100.0)
HPV 16 cLIA ≥20 mMU/mL Number Analyzed 529 participants 542 participants 556 participants
100.0
(99.3 to 100.0)
100.0
(99.3 to 100.0)
99.6
(98.7 to 100.0)
HPV 18 cLIA ≥24 mMU/mL Number Analyzed 531 participants 547 participants 563 participants
99.8
(99.0 to 100.0)
100.0
(99.3 to 100.0)
99.6
(98.7 to 100.0)
HPV 31 cLIA ≥10 mMU/mL Number Analyzed 522 participants 542 participants 553 participants
100.0
(99.3 to 100.0)
100.0
(99.3 to 100.0)
99.8
(99.0 to 100.0)
HPV 33 cLIA ≥8 mMU/mL Number Analyzed 534 participants 543 participants 560 participants
100.0
(99.3 to 100.0)
100.0
(99.3 to 100.0)
99.6
(98.7 to 100.0)
HPV 45 cLIA ≥8 mMU/mL Number Analyzed 534 participants 548 participants 565 participants
99.8
(99.0 to 100.0)
100.0
(99.3 to 100.0)
99.6
(98.7 to 100.0)
HPV 52 cLIA ≥8 mMU/mL Number Analyzed 533 participants 547 participants 562 participants
100.0
(99.3 to 100.0)
100.0
(99.3 to 100.0)
99.6
(98.7 to 100.0)
HPV 58 cLIA ≥8 mMU/mL Number Analyzed 531 participants 539 participants 560 participants
100.0
(99.3 to 100.0)
100.0
(99.3 to 100.0)
99.6
(98.7 to 100.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 6
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.9 to 0.9
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 6
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-0.4 to 1.7
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 6
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-0.4 to 1.7
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 11
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 0.7
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 11
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.4 to 1.3
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 11
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.4 to 1.3
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 16
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 0.7
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 16
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.4 to 1.3
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 16
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.4 to 1.3
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 18
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.1 to 0.5
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 18
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.7 to 1.1
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 18
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.4 to 1.3
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 31
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 0.7
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 31
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.6 to 1.0
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 31
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.5 to 1.0
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 33
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 0.7
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 33
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.4 to 1.3
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 33
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.4 to 1.3
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 45
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-1.1 to 0.5
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 45
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.7 to 1.1
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 45
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.4 to 1.3
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 52
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 0.7
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 52
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.3
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 52
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.4 to 1.3
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 2)
Comments Anti-HPV 58
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.7 to 0.7
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 2)
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 1), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 58
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.4 to 1.3
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 1) minus 9- to 15-Year-Old Females (Lot 3)
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Base Study: 9- to 15-Year-Old Females (Lot 2), Base Study: 9- to 15-Year-Old Females (Lot 3)
Comments Anti-HPV 58
Type of Statistical Test Equivalence
Comments equivalence requires that the two-sided 95% CI for the difference in percentages between lots be entirely contained within the interval (-5, 5).
Method of Estimation Estimation Parameter Percentage Point Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.4 to 1.3
Estimation Comments Percentage Point Difference = 9- to 15-Year-Old Females (Lot 2) minus 9- to 15-Year-Old Females (Lot 3)
12.Secondary Outcome
Title Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Females
Hide Description Persistent infection is when a participant is positive by polymerase chain reaction (PCR) for the same HPV type in cervicovaginal/external genital swabs or tissue specimens collected at consecutive visits at least 6 months (+/-1 month visit window) apart. Incidence was estimated as cases per 10,000 person-years. Person-years follow-up was from beginning of long-term follow-up or when a study participant reached 16 years of age, whichever came later. Per protocol, the extension study included 9- to 15-year-old females regardless of lot administered.
Time Frame Up to ~Month 126
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol effectiveness population, which included participants who were seronegative (by cLIA) to the relevant HPV type(s) at Day 1 (seronegative to both HPV 6 and 11 for analysis of HPV 6 and 11 HPV11-related endpoints), received all 3 doses of 9vHPV vaccine with the correct dose of the clinical material within 1 year, and had no other protocol violation that could interfere with evaluation of vaccine effectiveness.
Arm/Group Title Extension Study: 9- to 15-Year-Old Females
Hide Arm/Group Description:
In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).
Overall Number of Participants Analyzed 872
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Cases per 10,000 person-years
52.4
(33.6 to 78.0)
13.Secondary Outcome
Title Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Males
Hide Description Persistent infection is when a participant is positive by PCR for the same HPV type in external genital swabs or tissue specimens collected at consecutive visits at least 6 months (+/-1 month visit window) apart. Incidence was estimated as cases per 10,000 person-years. Person-years follow-up was from beginning of long-term follow-up or when a study participant reached 16 years of age, whichever came later.
Time Frame Up to ~Month 126
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol effectiveness population, which included participants who were seronegative (by cLIA) to the relevant HPV type(s) at Day 1 (seronegative to both HPV 6 and 11 for analysis of HPV 6 and 11-related endpoints), received all 3 doses of 9vHPV vaccine with the correct dose of the clinical material within 1 year, and had no other protocol violation that could interfere with evaluation of vaccine effectiveness.
Arm/Group Title Extension Study: 9- to 15-Year-Old Males
Hide Arm/Group Description:
In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).
Overall Number of Participants Analyzed 261
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Cases per 10,000 person-years
54.6
(21.9 to 112.4)
14.Secondary Outcome
Title Extension Study: Combined Incidence of Cervical Intraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia, Vaginal Intraepithelial Neoplasia, Genital Warts, and Cervical/Vulvar/Vaginal Cancers Related to HPV 6/11/16/18/31/33/45/52/58 in Females
Hide Description The combined incidence of cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, genital warts, and cervical/vulvar/vaginal cancers, related to HPV 6/11/16/18/31/33/45/52/58 was assessed. This outcome measure was determined by clinical/pathologic criteria and positive PCR assay for HPV type. Incidence was estimated as cases per 10,000 person-years. Person-years follow-up was calculated starting from the beginning of the long-term follow-up study or the date when the study participant reached 16 years of age, whichever came later. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.
Time Frame Up to ~Month 126
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol effectiveness population, which included participants who were seronegative (by cLIA) to the relevant HPV type(s) at Day 1 (seronegative to both HPV 6 and 11 for analysis of HPV 6 and 11-related endpoints), received all 3 doses of 9vHPV vaccine with the correct dose of the clinical material within 1 year, and had no other protocol violation that could interfere with evaluation of vaccine effectiveness.
Arm/Group Title Extension Study: 9- to 15-Year-Old Females
Hide Arm/Group Description:
In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).
Overall Number of Participants Analyzed 866
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Cases per 10,000 person-years
2.2
(0.1 to 12.2)
15.Secondary Outcome
Title Extension Study: Combined Incidence of Penile Intraepithelial Neoplasia, Penile/Perineal/Perianal Cancers and Genital Warts Related to HPV 6/11/16/18/31/33/45/52/58 in Males
Hide Description The combined incidence of penile intraepithelial neoplasia, penile/perineal/perianal cancers, and genital warts related to HPV6/11/16/18/31/33/45/52/58 was assessed. This outcome measure was determined by clinical/pathologic criteria and positive PCR assay for HPV type. Incidence was estimated as cases per 10,000 person-years. For each study participant, person-years follow up was calculated starting from the beginning of the long-term follow-up study or the date when the study participant reached 16 years of age, whichever came later.
Time Frame Up to ~Month 126
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol effectiveness population, which included participants who were seronegative (by cLIA) to the relevant HPV type(s) at Day 1 (seronegative to both HPV 6 and 11 for analysis of HPV 6 and 11-related endpoints), received all 3 doses of 9vHPV vaccine with the correct dose of the clinical material within 1 year, and had no other protocol violation that could interfere with evaluation of vaccine effectiveness.
Arm/Group Title Extension Study: 9- to 15-Year-Old Males
Hide Arm/Group Description:
In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).
Overall Number of Participants Analyzed 261
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Cases per 10,000 person-years
0.0
(0.0 to 28.9)
16.Secondary Outcome
Title Extension Study: Percentage of Participants With Vaccine-Related or Procedure-Related Serious Adverse Events
Hide Description A serious adverse event (SAE) included a death which resulted in the participant discontinuing the study, a serious adverse experience that was considered by an investigator who was a qualified physician to be possibly, probably, or definitely vaccine related or study procedure related. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.
Time Frame Up to ~Month 126
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 study vaccination in the base study and had follow-up data.
Arm/Group Title Extension Study: 9- to 15-Year-Old Females Extension Study: 9- to 15-Year-Old Males
Hide Arm/Group Description:
In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).
In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension studies, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1) and for immunogenicity, effectiveness, and safety up to Month 126 (EXT2)
Overall Number of Participants Analyzed 971 301
Measure Type: Number
Unit of Measure: Percentage of Participants
0.0 0.0
Time Frame Base Study: Up to ~12 months; Extension Study: Up to ~126 months
Adverse Event Reporting Description Base Study and Extension Study: ACM was analyzed in all randomized participants. Safety was analyzed in all participants who received at least one dose of 9vHPV and had available follow-up data, per protocol. ACM and safety were reported separately for base study, first extension (EXT1) and second extension (EXT2).
 
Arm/Group Title Base Study: 9- to 15-Year-Old Females (Lot 1) Base Study: 9- to 15-Year-Old Females (Lot 2) Base Study: 9- to 15-Year-Old Females (Lot 3) Base Study: 9- to 15-Year-Old Males (Lot 1) Base Study: 16- to 26-Year-Old Females (Lot 1) EXT1: 9- to 15-Year-Old Females EXT1: 9- to 15-Year-Old Males EXT2: 9- to 15-Year-Old Females EXT2: 9- to 15-Year-Old Males
Hide Arm/Group Description 9-valent human papillomavirus (9vHPV) L1 virus-like particle (VLP) vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1. 9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 2. 9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 3. 9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1. 9vHPV L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Vaccine dose administered was obtained from manufacturing Lot 1. In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension study, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1). In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension study, the participants were followed up for safety and immunogenicity up to Month 36 (EXT1). In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension study, the participants were followed up for immunogenicity, effectiveness, and safety up to Month 126 (EXT2). In the base study, participants received the 9vHPV L1 VLP vaccine (0.5 mL intramuscular injection) at Day 1, Month 2, and Month 6 and were evaluated through Month 12. In the extension study, the participants were followed up for immunogenicity, effectiveness, and safety up to Month 126 (EXT2).
All-Cause Mortality
Base Study: 9- to 15-Year-Old Females (Lot 1) Base Study: 9- to 15-Year-Old Females (Lot 2) Base Study: 9- to 15-Year-Old Females (Lot 3) Base Study: 9- to 15-Year-Old Males (Lot 1) Base Study: 16- to 26-Year-Old Females (Lot 1) EXT1: 9- to 15-Year-Old Females EXT1: 9- to 15-Year-Old Males EXT2: 9- to 15-Year-Old Females EXT2: 9- to 15-Year-Old Males
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/648 (0.00%)      0/643 (0.00%)      0/644 (0.00%)      0/669 (0.00%)      0/470 (0.00%)      1/1604 (0.06%)      0/568 (0.00%)      1/971 (0.10%)      0/301 (0.00%)    
Hide Serious Adverse Events
Base Study: 9- to 15-Year-Old Females (Lot 1) Base Study: 9- to 15-Year-Old Females (Lot 2) Base Study: 9- to 15-Year-Old Females (Lot 3) Base Study: 9- to 15-Year-Old Males (Lot 1) Base Study: 16- to 26-Year-Old Females (Lot 1) EXT1: 9- to 15-Year-Old Females EXT1: 9- to 15-Year-Old Males EXT2: 9- to 15-Year-Old Females EXT2: 9- to 15-Year-Old Males
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/643 (0.93%)      2/639 (0.31%)      8/641 (1.25%)      11/662 (1.66%)      15/466 (3.22%)      2/1604 (0.12%)      0/568 (0.00%)      3/971 (0.31%)      0/301 (0.00%)    
Gastrointestinal disorders                   
Abdominal pain  1  0/643 (0.00%)  0 0/639 (0.00%)  0 0/641 (0.00%)  0 0/662 (0.00%)  0 1/466 (0.21%)  3 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Colitis  1  0/643 (0.00%)  0 0/639 (0.00%)  0 1/641 (0.16%)  1 0/662 (0.00%)  0 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Colitis ulcerative  1  1/643 (0.16%)  1 0/639 (0.00%)  0 0/641 (0.00%)  0 0/662 (0.00%)  0 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Gastritis  1  0/643 (0.00%)  0 0/639 (0.00%)  0 1/641 (0.16%)  1 0/662 (0.00%)  0 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
General disorders                   
Pyrexia  1  0/643 (0.00%)  0 0/639 (0.00%)  0 1/641 (0.16%)  1 0/662 (0.00%)  0 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Hepatobiliary disorders                   
Biliary colic  1  0/643 (0.00%)  0 0/639 (0.00%)  0 0/641 (0.00%)  0 0/662 (0.00%)  0 1/466 (0.21%)  1 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Infections and infestations                   
Appendicitis  1  1/643 (0.16%)  1 1/639 (0.16%)  1 0/641 (0.00%)  0 3/662 (0.45%)  3 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Disseminated tuberculosis  1  0/643 (0.00%)  0 0/639 (0.00%)  0 0/641 (0.00%)  0 0/662 (0.00%)  0 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 1/971 (0.10%)  1 0/301 (0.00%)  0
Gastroenteritis  1  0/643 (0.00%)  0 0/639 (0.00%)  0 0/641 (0.00%)  0 1/662 (0.15%)  1 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Gastrointestinal infection  1  0/643 (0.00%)  0 0/639 (0.00%)  0 1/641 (0.16%)  1 0/662 (0.00%)  0 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Infectious mononucleosis  1  0/643 (0.00%)  0 0/639 (0.00%)  0 1/641 (0.16%)  1 0/662 (0.00%)  0 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Paronychia  1  0/643 (0.00%)  0 0/639 (0.00%)  0 1/641 (0.16%)  1 0/662 (0.00%)  0 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Pharyngotonsillitis  1  0/643 (0.00%)  0 0/639 (0.00%)  0 0/641 (0.00%)  0 1/662 (0.15%)  1 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Pneumonia  1  1/643 (0.16%)  1 0/639 (0.00%)  0 0/641 (0.00%)  0 0/662 (0.00%)  0 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Sepsis  1  0/643 (0.00%)  0 0/639 (0.00%)  0 0/641 (0.00%)  0 0/662 (0.00%)  0 0/466 (0.00%)  0 1/1604 (0.06%)  1 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Tonsillitis  1  0/643 (0.00%)  0 0/639 (0.00%)  0 1/641 (0.16%)  1 0/662 (0.00%)  0 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Upper respiratory tract infection  1  1/643 (0.16%)  1 0/639 (0.00%)  0 0/641 (0.00%)  0 0/662 (0.00%)  0 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Urinary tract infection  1  0/643 (0.00%)  0 0/639 (0.00%)  0 0/641 (0.00%)  0 0/662 (0.00%)  0 1/466 (0.21%)  1 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Injury, poisoning and procedural complications                   
Ankle fracture  1  0/643 (0.00%)  0 0/639 (0.00%)  0 0/641 (0.00%)  0 1/662 (0.15%)  1 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Concussion  1  0/643 (0.00%)  0 0/639 (0.00%)  0 1/641 (0.16%)  1 0/662 (0.00%)  0 1/466 (0.21%)  1 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Foot fracture  1  0/643 (0.00%)  0 0/639 (0.00%)  0 0/641 (0.00%)  0 0/662 (0.00%)  0 1/466 (0.21%)  1 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Gun shot wound  1  0/643 (0.00%)  0 0/639 (0.00%)  0 0/641 (0.00%)  0 0/662 (0.00%)  0 1/466 (0.21%)  1 0/1604 (0.00%)  0 0/568 (0.00%)  0 0/971 (0.00%)  0 0/301 (0.00%)  0
Limb injury  1  0/643 (0.00%)  0 0/639 (0.00%)  0 0/641 (0.00%)  0 1/662 (0.15%)  1 0/466 (0.00%)  0 0/1604 (0.00%)  0 0/568 (0.00%)  0