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Cervical Intraepithelial Neoplasm (CIN) in Women (Gardasil) (V501-015) (FUTURE II)

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: NCT00092534
Recruitment Status : Active, not recruiting
First Posted : September 28, 2004
Results First Posted : November 26, 2009
Last Update Posted : March 4, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Cervical Cancer
Genital Warts
Interventions Biological: Gardasil, human papillomavirus (type 6, 11, 16, 18) recombinant vaccine
Biological: Matching Placebo
Enrollment 12167
Recruitment Details Female participants were randomized to receive quadrivalent human papillomavirus (qHPV) vaccine (GARDASIL™) or placebo in the Base Study (V501-015, NCT00092534), and were followed for 4 years. Participants who received placebo in the Base Study were eligible to receive the 3-dose qHPV vaccine series during the Base Study Extension (EXT).
Pre-assignment Details

Participants who received 3 doses of qHPV vaccine either during the Base Study or Base Study EXT were eligible for enrollment in the Long-Term Follow-Up (LTFU) Study (V501-015-21).

The 10-year-long registry-based LTFU was conducted at 4 National Registry Study Centers (NRSC) in Denmark, Iceland, Norway, and Sweden.

Arm/Group Title Base Study Group 1: qHPV Vaccine Base Study Group 2: Placebo Base Study EXT LTFU: Cohort 1 LTFU: Cohort 2
Hide Arm/Group Description During the Base Study, participants received 3 qHPV vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years. During the Base Study, participants received 3 placebo vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years. Participants who received placebo (N=581) or an incomplete qHPV vaccine regimen (N=13) were enrolled to receive qHPV vaccine during the base study extension; participants designated as "Not Completed" are those who did not complete all three vaccinations and/or all required follow-up visits. Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination. Participants who received placebo in the Base Study and qHPV vaccine after completion of the Base Study and prior to entry into the LTFU. Cohort 2 provided a total of approximately 10 years of follow-up post-vaccination.
Period Title: Base Study Vaccination Period
Started 6087 6080 0 0 0
Completed 5916 5954 0 0 0
Not Completed 171 126 0 0 0
Reason Not Completed
Randomized not Vaccinated             5             5             0             0             0
Adverse Event             3             1             0             0             0
Death             5             4             0             0             0
Lost to Follow-up             41             37             0             0             0
Physician Decision             1             0             0             0             0
Pregnancy             9             7             0             0             0
Protocol Violation             2             1             0             0             0
Withdrawal by Subject             85             58             0             0             0
Moved             14             12             0             0             0
New Medical History (Not AEs)             5             0             0             0             0
Travel             1             0             0             0             0
Site Closed             0             1             0             0             0
Period Title: Base Study Follow-Up Period
Started 5942 [1] 5971 [1] 0 0 0
Completed 5626 5277 0 0 0
Not Completed 316 694 0 0 0
Reason Not Completed
Adverse Event             2             4             0             0             0
Death             2             1             0             0             0
Lost to Follow-up             120             146             0             0             0
Pregnancy             6             10             0             0             0
Protocol Violation             1             2             0             0             0
Withdrawal by Subject             71             62             0             0             0
Moved             62             58             0             0             0
Travel             10             7             0             0             0
Site Closed             0             2             0             0             0
Subjects continuing             27             31             0             0             0
Subjects in extension             15             371             0             0             0
[1]
Includes subjects who did not receive 3 doses of vaccine/placebo but continued into the follow-up.
Period Title: Base Study EXT
Started 0 0 594 0 0
Completed 0 0 449 0 0
Not Completed 0 0 145 0 0
Reason Not Completed
Lost to Follow-up             0             0             41             0             0
Physician Decision             0             0             1             0             0
Pregnancy             0             0             12             0             0
Withdrawal by Subject             0             0             18             0             0
Participant moved             0             0             6             0             0
Travel             0             0             2             0             0
Site closed             0             0             21             0             0
Study ended             0             0             29             0             0
Protocol Violation             0             0             15             0             0
Period Title: Long-Term Follow-Up (LTFU) Study
Started [1] 0 0 0 2750 [2] 2097 [2]
Started: Registry-based Effectiveness [3] 0 0 0 2650 2050
Started: Immunogenicity Analysis [4] 0 0 0 2385 1849
Started: Registry-based Safety [5] 0 0 0 2448 1888
Completed 0 0 0 2749 2097
Not Completed 0 0 0 1 0
Reason Not Completed
Withdrawal by Subject             0             0             0             1             0
[1]
Eligible for inclusion in the LTFU study
[2]
Some Base Study participants did not consent for inclusion in the LTFU.
[3]
Eligible and consented to inclusion in registry-based searches for effectiveness information
[4]
Eligible and consented to provide blood samples for immunogenicity anaysis
[5]
Eligible and consented to inclusion in registry-based searches for safety information
Arm/Group Title Base Study Group 1: qHPV Vaccine Base Study Group 2: Placebo Total
Hide Arm/Group Description During the Base Study, participants received 3 qHPV vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years. During the Base Study, participants received 3 placebo vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years. Total of all reporting groups
Overall Number of Baseline Participants 6087 6080 12167
Hide Baseline Analysis Population Description
The Baseline Analysis population is from the V501-015 Base Study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6087 participants 6080 participants 12167 participants
20.0  (2.2) 19.9  (2.1) 19.9  (2.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6087 participants 6080 participants 12167 participants
Female
6087
 100.0%
6080
 100.0%
12167
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6087 participants 6080 participants 12167 participants
Asian
151
   2.5%
135
   2.2%
286
   2.4%
Black
171
   2.8%
227
   3.7%
398
   3.3%
Hispanic American
555
   9.1%
557
   9.2%
1112
   9.1%
Native American
1
   0.0%
1
   0.0%
2
   0.0%
White
4584
  75.3%
4550
  74.8%
9134
  75.1%
Other-Unspecified
625
  10.3%
610
  10.0%
1235
  10.2%
1.Primary Outcome
Title Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 16/18-related Cervical Intraepithelial Neoplasia (CIN) 2 or Worse in the Base Study
Hide Description This measure is defined to have occurred when, on a single cervical biopsy, endocervical curettage (ECC), loop electrosurgical excision procedure (LEEP), or conization specimen, there was HPV Vaccine consensus diagnosis of CIN 2 or worse up to 4 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, adenocarcinoma in situ (AIS) or cervical cancer related to HPV 16 or 18.
Time Frame Up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received 3 qHPV doses in 1 year, had no protocol violations that could affect evaluation of vaccine efficacy, were polymerase chain reaction (PCR)-negative and seronegative based on competitive Luminex immunoassay (cLIA) to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7, and had data available.
Arm/Group Title Base Study Group 1: qHPV Vaccine Base Study Group 2: Placebo
Hide Arm/Group Description:
During the Base Study, participants received 3 qHPV vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years.
During the Base Study, participants received 3 placebo vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years.
Overall Number of Participants Analyzed 5306 5262
Measure Type: Number
Unit of Measure: Incidence per 100 person-years
0.0 0.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Base Study Group 1: qHPV Vaccine, Base Study Group 2: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent relative risk reduction
Estimated Value 96.6
Confidence Interval 95%
88.2 to 99.6
Estimation Comments Confidence Interval (CI) based on binomial tail probabilities and not from a dispersion parameter
2.Primary Outcome
Title Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 16/18-related Cervical Intraepithelial Neoplasia (CIN) 2 or Worse in the Long-term Follow-up (LTFU) Study
Hide Description This measure is defined to have occurred when, on a single cervical biopsy, endocervical curettage (ECC), loop electrosurgical excision procedure (LEEP), or conization specimen, there was HPV Vaccine Nordic pathology panel (NPP) consensus diagnosis of CIN 2 or worse up to 14 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, AIS or cervical cancer related to HPV 16 or 18. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU are included. Because the objective was to demonstrate qHPV vaccine prophylactic efficacy at 14 years, Cohort 2 was not included in the analysis.
Time Frame Up to 14 years since Vaccine Dose 1
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Cohort 1 who received 3 qHPV vaccine doses in 1 year, had no protocol violations that could affect evaluation of efficacy, had been PCR-negative and seronegative based on cLIA at Day 1 and PCR-negative through Month 7 of the Base Study to the relevant HPV type(s), and had LTFU data available.
Arm/Group Title LTFU: Cohort 1
Hide Arm/Group Description:
Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed 2121
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Incidence per 100 person-years
0.0
(0.0 to 0.1)
3.Primary Outcome
Title Incidence of the Composite Endpoint of HPV16/18-related CIN 2 or Worse in the Long-term Follow-up (LTFU) Study
Hide Description This measure is defined to have occurred when, on a single cervical biopsy, ECC, LEEP, or conization specimen, there was HPV Vaccine NPP consensus diagnosis of CIN 2 or worse up to 22 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, AIS or cervical cancer related to HPV 16 or 18. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU will be included.
Time Frame up to 22 years post Vaccination Dose 1
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Number of Participants With Anti-Human Papillomavirus (HPV) 6 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study
Hide Description Anti-HPV levels >20 mMU/mL neutralize a large input load of HPV 6 pseudovirions in vitro; thus, the number of participants with anti-HPV 6 ≥20 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined.
Time Frame Month 7 (4 weeks after Vaccination 3)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received 3 qHPV vaccine doses and had Month 7 results within acceptable ranges, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were polymerase chain reaction (PCR)-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
Arm/Group Title Base Study Group 1: qHPV Vaccine Base Study Group 2: Placebo
Hide Arm/Group Description:
During the Base Study, participants received 3 qHPV vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years.
During the Base Study, participants received 3 placebo vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years.
Overall Number of Participants Analyzed 1056 1057
Measure Type: Number
Unit of Measure: Number of Participants
1054 13
5.Secondary Outcome
Title Number of Participants With Anti-Human Papillomavirus (HPV) 11 Titer ≥16 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study
Hide Description Anti-HPV levels >20 mMU/mL neutralize a large input load of HPV 11 virions in vitro; thus, the number of participants with anti-HPV 11 ≥16 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined.
Time Frame Week 4 Postdose 3
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received 3 qHPV vaccine doses and had Month 7 results within acceptable ranges, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were polymerase chain reaction (PCR)-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
Arm/Group Title Base Study Group 1: qHPV Vaccine Base Study Group 2: Placebo
Hide Arm/Group Description:
During the Base Study, participants received 3 qHPV vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years.
During the Base Study, participants received 3 placebo vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years.
Overall Number of Participants Analyzed 1057 1057
Measure Type: Number
Unit of Measure: Number of Participants
1054 5
6.Secondary Outcome
Title Number of Participants With Anti-Human Papillomavirus (HPV) 16 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study
Hide Description Anti-HPV levels >20 mMU/mL neutralize a large input load of HPV 16 pseudovirions in vitro; thus, the number of participants with anti-HPV 16 ≥20 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined.
Time Frame Week 4 Postdose 3
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received 3 qHPV vaccine doses and had Month 7 results within acceptable ranges, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were polymerase chain reaction (PCR)-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
Arm/Group Title Base Study Group 1: qHPV Vaccine Base Study Group 2: Placebo
Hide Arm/Group Description:
During the Base Study, participants received 3 qHPV vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years.
During the Base Study, participants received 3 placebo vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years.
Overall Number of Participants Analyzed 1017 994
Measure Type: Number
Unit of Measure: Number of Participants
1014 15
7.Secondary Outcome
Title Number of Participants With Anti-Human Papillomavirus (HPV) 18 Titer ≥24 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study
Hide Description Anti-HPV levels >20 mMU/mL neutralize a large input load of HPV 18 pseudovirions in vitro; thus, the number of participants with anti-HPV 18 ≥24 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined.
Time Frame Week 4 Postdose 3
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received 3 qHPV vaccine doses and had Month 7 results within acceptable ranges, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were polymerase chain reaction (PCR)-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
Arm/Group Title Base Study Group 1: qHPV Vaccine Base Study Group 2: Placebo
Hide Arm/Group Description:
During the Base Study, participants received 3 qHPV vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years.
During the Base Study, participants received 3 placebo vaccinations (at Day 1, Month 2 and Month 6) and were followed for up to 4 years.
Overall Number of Participants Analyzed 1140 1119
Measure Type: Number
Unit of Measure: Number of Participants
1133 12
8.Secondary Outcome
Title Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 31/33/35/39/45/51/52/56/58/59-related Cervical Intraepithelial Neoplasia (CIN) Grade 2 or Worse in the Long-term Follow-up (LTFU) Study
Hide Description This measure is defined to have occurred when, on a single cervical biopsy, endocervical curettage (ECC), loop electrosurgical excision procedure (LEEP), or conization specimen, there was HPV Vaccine Nordic pathology panel (NPP) consensus diagnosis of CIN 2 or worse related to nonvaccine HPV types up to 14 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, AIS or cervical cancer related to nonvaccine HPV types 31, 33, 35, 39, 45, 51, 52, 56, 58, or 59. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU are included. Because the objective was to demonstrate qHPV vaccine prophylactic efficacy at 14 years, Cohort 2 was not included in the analysis.
Time Frame Up to 14 years since Vaccination Dose 1
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Cohort 1 who had received ≥1 qHPV vaccination, had any follow up visit in the LTFU, and had been PCR-negative and seronegative based on cLIA to the appropriate HPV type(s) at Day 1.
Arm/Group Title LTFU: Cohort 1
Hide Arm/Group Description:
Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed 2355
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Incidence per 100 person-years
0.2
(0.1 to 0.2)
9.Secondary Outcome
Title Incidence of the Composite Endpoint of HPV 6/11/16/18-related CIN (Any Grade), AIS, Cervical Cancer, Vulvar Cancer or Vaginal Cancer the Long-term Follow-up (LTFU) Study
Hide Description This measure was defined to have occurred if on a single biopsy or excised tissue, there was the NPP consensus diagnosis of CIN 1, CIN 2, CIN 3, AIS, cervical cancer, vulvar cancer or vaginal cancer AND at least 1 of HPV types 6, 11, 16 or 18 was detected by Thin-section PCR in an adjacent section from the same tissue block. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU are included. Because the objective was to demonstrate qHPV vaccine prophylactic efficacy at 14 years, Cohort 2 was not included in the analysis.
Time Frame Up to 14 years since Vaccination Dose 1
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Cohort 1 who received 3 qHPV vaccine doses in 1 year, had no protocol violations that could affect efficacy, had been PCR-negative and seronegative based on cLIA at Day 1 and PCR-negative through Month 7 of the Base Study to relevant HPV type(s), and had LTFU data available.
Arm/Group Title LTFU: Cohort 1
Hide Arm/Group Description:
Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed 2312
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Incidence per 100 person-years
0.1
(0.1 to 0.1)
10.Secondary Outcome
Title Incidence of the Composite Endpoint of HPV 6/11/16/18-related CIN (Any Grade), AIS, Cervical Cancer, Vulvar Cancer or Vaginal Cancer the Long-term Follow-up (LTFU) Study
Hide Description This measure is defined to have occurred if on a single biopsy or excised tissue, there is the NPP consensus diagnosis of CIN 1, CIN 2, CIN 3, AIS, cervical cancer, vulvar cancer or vaginal cancer AND at least 1 of HPV types 6, 11, 16 or 18 is detected by Thin-section PCR in an adjacent section from the same tissue block.
Time Frame up to 22 years since Vaccination Dose 1
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study
Hide Description Antibodies to human papillomavirus (HPV) types were measured using cLIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time Frame At 108 months since Vaccination Dose 1
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Cohort 1 who received 3 qHPV vaccine doses in 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were PCR-negative and seronegative based on cLIA to relevant type at Day 1 and PCR-negative to the relevant type through Month 7. No data were collected for Cohort 2.
Arm/Group Title LTFU: Cohort 1
Hide Arm/Group Description:
Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed 2750
Geometric Mean (95% Confidence Interval)
Unit of Measure: mMU/mL
Anti-HPV 6 Number Analyzed 1234 participants
89.2
(84.7 to 94.0)
Anti-HPV 11 Number Analyzed 1234 participants
85.2
(80.7 to 90.0)
Anti-HPV 16 Number Analyzed 1179 participants
348.6
(328.3 to 370.2)
Anti-HPV 18 Number Analyzed 1332 participants
32.5
(30.2 to 34.9)
12.Secondary Outcome
Title Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study
Hide Description Antibodies to human papillomavirus (HPV) types were measured using cLIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time Frame At 168 months since Vaccination Dose 1
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
Arm/Group Title LTFU: Cohort 1
Hide Arm/Group Description:
Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed 2750
Geometric Mean (95% Confidence Interval)
Unit of Measure: mMU/mL
Anti-HPV 6 Number Analyzed 1058 participants
78.4
(73.8 to 83.2)
Anti-HPV 11 Number Analyzed 1058 participants
66.8
(62.6 to 71.3)
Anti-HPV 16 Number Analyzed 1005 participants
291.2
(272.1 to 311.5)
Anti-HPV 18 Number Analyzed 1131 participants
26.1
(24.1 to 28.2)
13.Secondary Outcome
Title Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study
Hide Description Antibodies to human papillomavirus (HPV) types were measured using cLIA. Seropositivity was assessed by competitive Luminex Immunoassay (cLIA); the serostatus cut-offs for anti-HPV 6, 11, 16 and 18 serum cLIA were 20, 16, 20 and 24 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time Frame At 108 months since Vaccination Dose 1
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7. No data were collected for Cohort 2.
Arm/Group Title LTFU: Cohort 1
Hide Arm/Group Description:
Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed 2750
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Anti-HPV 6 Number Analyzed 1234 participants
94.4
(93.0 to 95.6)
Anti-HPV 11 Number Analyzed 1234 participants
95.5
(94.1 to 96.6)
Anti-HPV 16 Number Analyzed 1179 participants
99.1
(98.3 to 99.5)
Anti-HPV 18 Number Analyzed 1332 participants
59.9
(57.2 to 62.6)
14.Secondary Outcome
Title Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study
Hide Description Antibodies to human papillomavirus (HPV) types were measured using cLIA. Seropositivity was assessed by cLIA; the serostatus cut-offs for anti-HPV 6, 11, 16 and 18 serum cLIA were 20, 16, 20 and 24 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time Frame At 168 months since Vaccination Dose 1
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, and were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
Arm/Group Title LTFU: Cohort 1
Hide Arm/Group Description:
Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed 2750
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Anti-HPV 6 Number Analyzed 1058 participants
90.6
(88.7 to 92.3)
Anti-HPV 11 Number Analyzed 1058 participants
91.1
(89.2 to 92.8)
Anti-HPV 16 Number Analyzed 1005 participants
98.3
(97.3 to 99.0)
Anti-HPV 18 Number Analyzed 1131 participants
52.4
(49.5 to 55.4)
15.Secondary Outcome
Title Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Hide Description Antibodies to human papillomavirus (HPV) types were measured using IgG LIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time Frame At 108 months since Vaccination Dose 1
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7. No data were collected for Cohort 2.
Arm/Group Title LTFU: Cohort 1
Hide Arm/Group Description:
Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed 2750
Geometric Mean (95% Confidence Interval)
Unit of Measure: mMU/mL
Anti-HPV 6 Number Analyzed 1235 participants
95.2
(90.5 to 100.1)
Anti-HPV 11 Number Analyzed 1235 participants
67.4
(64.3 to 70.8)
Anti-HPV 16 Number Analyzed 1181 participants
346.1
(327.3 to 365.9)
Anti-HPV 18 Number Analyzed 1333 participants
46.1
(43.3 to 49.2)
16.Secondary Outcome
Title Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Hide Description Antibodies to human papillomavirus (HPV) types were measured using IgG LIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time Frame At 168 months since Vaccination Dose 1
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
Arm/Group Title LTFU: Cohort 1
Hide Arm/Group Description:
Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed 2750
Geometric Mean (95% Confidence Interval)
Unit of Measure: mMU/mL
Anti-HPV 6 Number Analyzed 1054 participants
81.2
(76.1 to 86.5)
Anti-HPV 11 Number Analyzed 1055 participants
53.5
(50.2 to 57.0)
Anti-HPV 16 Number Analyzed 1000 participants
290.2
(271.0 to 310.8)
Anti-HPV 18310.8 Number Analyzed 1036 participants
36.5
(33.7 to 39.5)
17.Secondary Outcome
Title Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Hide Description Antibodies to HPV types were measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 at Month 108 were 15, 15, 7, and 10 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time Frame At 108 months since Vaccination Dose 1
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7. No data were collected for Cohort 2.
Arm/Group Title LTFU: Cohort 1
Hide Arm/Group Description:
Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed 2750
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Anti-HPV 6 Number Analyzed 1235 participants
97.6
(96.6 to 98.4)
Anti-HPV 11 Number Analyzed 1235 participants
96.3
(95.1 to 97.3)
Anti-HPV 16 Number Analyzed 1181 participants
100.0
(99.7 to 100.0)
Anti-HPV 18 Number Analyzed 1333 participants
91.4
(89.7 to 92.8)
18.Secondary Outcome
Title Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Hide Description Antibodies to HPV types were measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 at Month 168 were 9, 6, 5, and 5 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Time Frame At 168 months since Vaccination Dose 1
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Cohort 1 who received 3 qHPV vaccine doses within 1 year, had no protocol violations that could affect evaluation of vaccine immunogenicity, were PCR-negative and seronegative based on cLIA to the relevant type at Day 1 and PCR-negative to the relevant type through Month 7.
Arm/Group Title LTFU: Cohort 1
Hide Arm/Group Description:
Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination.
Overall Number of Participants Analyzed 2750
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Anti-HPV 6 Number Analyzed 1054 participants
98.1
(97.1 to 98.8)
Anti-HPV 11 Number Analyzed 1055 participants
98.0
(97.0 to 98.8)
Anti-HPV 16 Number Analyzed 1000 participants
100.0
(99.6 to 100.0)
Anti-HPV 18 Number Analyzed 1036 participants
93.8
(92.2 to 95.2)
19.Secondary Outcome
Title Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 216 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Hide Description Antibodies to human papillomavirus (HPV) types will be measured using IgG LIA..
Time Frame At 216 months since Vaccination Dose 1
Outcome Measure Data Not Reported
20.Secondary Outcome
Title Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 216 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) ) in the Long-Term Follow-Up (LTFU) Study
Hide Description Antibodies to HPV types will be measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 are 15, 15, 7, and 10 milliMerck units (mMU)/mL, respectively. The percentage of participants that are seropositive for each type will be summarized.
Time Frame At 216 months since Vaccination Dose 1
Outcome Measure Data Not Reported
21.Secondary Outcome
Title Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 264 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Hide Description Antibodies to human papillomavirus (HPV) types will be measured using IgG LIA..
Time Frame At 264 months since Vaccination Dose 1
Outcome Measure Data Not Reported
22.Secondary Outcome
Title Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 264 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study
Hide Description Antibodies to HPV types will be measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 are 15, 15, 7, and 10 milliMerck units (mMU)/mL, respectively. The percentage of participants that are seropositive for each type will be summarized.
Time Frame At 264 months since Vaccination Dose 1
Outcome Measure Data Not Reported
Time Frame From randomization in the Base Study to up to 10 years after completion of the Base Study (up to 14 years)
Adverse Event Reporting Description The number of participants at risk includes randomized participants who had follow-up data available. Both serious adverse events (SAEs) and nonserious AEs were collected in the Base Study. Safety data for the LTFU were evaluated based on health outcomes data available from the national registries; in addition, AEs and SAEs associated with blood draws at LTFU Year 5 and Year 10 were also collected.
 
Arm/Group Title Base Study Group 1: qHPV Vaccine Base Study Group 2: Placebo Base Study EXT LTFU: Cohort 1 LTFU: Cohort 2
Hide Arm/Group Description During the Base Study, participants received 3 qHPV vaccinations (at Day 1, Month 2 and Month 6) during the Vaccination Period and were followed for up to 4 years during the Base Study Follow-Up. Participants received 3 placebo vaccinations (at Day 1, Month 2 and Month 6) during the Base Study Vaccination Period, and then received 3 qHPV vaccinations during the 4-year Base Study EXT. Participants who received placebo (N=581) or an incomplete qHPV vaccine regimen (N=13) were enrolled to receive qHPV vaccine during the base study extension; participants designated as "Not Completed" are those who did not complete all three vaccinations and/or all required follow-up visits. Participants who received qHPV vaccine in the Base Study with approximately 4 years of follow-up in the Base Study and 10 years of follow-up in the LTFU. Cohort 1 provided a total of approximately 14 years of follow-up post-vaccination. Participants who received placebo in the Base Study and qHPV vaccine after completion of the Base Study and prior to entry into the LTFU. Cohort 2 provided a total of approximately 10 years of follow-up post-vaccination in the LTFU.
All-Cause Mortality
Base Study Group 1: qHPV Vaccine Base Study Group 2: Placebo Base Study EXT LTFU: Cohort 1 LTFU: Cohort 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/6082 (0.12%)   5/6075 (0.08%)   0/594 (0.00%)   2/2448 (0.08%)   1/1888 (0.05%) 
Hide Serious Adverse Events
Base Study Group 1: qHPV Vaccine Base Study Group 2: Placebo Base Study EXT LTFU: Cohort 1 LTFU: Cohort 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   46/6082 (0.76%)   56/6075 (0.92%)   1/594 (0.17%)   0/2448 (0.00%)   0/1888 (0.00%) 
Blood and lymphatic system disorders           
Disseminated intravascular coagulation * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Cardiac disorders           
Aortic valve disease * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Cardiac arrest * 1  1/6021 (0.02%)  0/6033 (0.00%)  0/594 (0.00%)  0/594 (0.00%)  0/1888 (0.00%) 
Myocarditis * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Pericarditis * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Gastrointestinal disorders           
Abdominal pain * 1  1/6082 (0.02%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Gastritis * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Reflux oesophagitis * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
General disorders           
Chills * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Face oedema * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Pyrexia * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Injection site joint movement impairment * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Injection site pain * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Hepatobiliary disorders           
Cholelithiasis * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Immune system disorders           
Anaphylactic reaction * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Hypersensitivty * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Infections and infestations           
Appendicitis * 1  2/6082 (0.03%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Cervicitis * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Endometritis * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Gastroenteritis * 1  2/6082 (0.03%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Gastrointestinal infection * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Infective thrombosis * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Pelvic Inflammatory disease * 1  0/6082 (0.00%)  2/6075 (0.03%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Pneumonia * 1  2/6082 (0.03%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Pyelonephritis * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Sepsis * 1  2/6082 (0.03%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Septic Shock * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Typhoid fever * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Urinary tract infection * 1  0/6082 (0.00%)  2/6075 (0.03%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Uterine infection * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Injury, poisoning and procedural complications           
Chemical poisoning * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Failed forceps delivery * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Intentional overdose * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Multiple injuries * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Overdose * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Post procedural haemorrhage * 1  1/6082 (0.02%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Road traffic accident * 1  3/6082 (0.05%)  2/6075 (0.03%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Thermal burn * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Musculoskeletal and connective tissue disorders           
Pain in extremity * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Thyroid cancer * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Nervous system disorders           
Convulsion * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Dizziness * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Headache * 1  2/6082 (0.03%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Pregnancy, puerperium and perinatal conditions           
Abortion threatened * 1  3/6082 (0.05%)  4/6075 (0.07%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Breech presentation * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Brow presentation * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Cephalo-pelvic disproportion * 1  0/6082 (0.00%)  5/6075 (0.08%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Cervix dystocia * 1  1/6082 (0.02%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Ectopic pregnancy  1  1/6082 (0.02%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Failed trial of labour * 1  3/6082 (0.05%)  3/6075 (0.05%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Foetal distress syndrome * 1  3/6082 (0.05%)  2/6075 (0.03%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Foetal malpresentation * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Hyperemesis gravidarum * 1  2/6082 (0.03%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Imminent abortion * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Oligohydramnios * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Postpartum haemorrhage * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Pre-eclampsia * 1  1/6082 (0.02%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Pregnancy induced hypertension * 1  2/6082 (0.03%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Premature labour * 1  3/6082 (0.05%)  5/6075 (0.08%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Premature rupture of membranes * 1  1/6082 (0.02%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Prolonged pregnancy * 1  0/6082 (0.00%)  2/6075 (0.03%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Uterine contractions during pregnancy * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Cervical incompetence * 1  0/6082 (0.00%)  2/6075 (0.03%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Psychiatric disorders           
Bipolar disorder * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Completed suicide * 1  0/6082 (0.00%)  2/6075 (0.03%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Panic attack * 1  0/6082 (0.00%)  0/6075 (0.00%)  1/594 (0.17%)  0/2448 (0.00%)  0/1888 (0.00%) 
Renal and urinary disorders           
Urinary retention * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Reproductive system and breast disorders           
Cervix haemorrhage uterine * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Ovarian cyst * 1  2/6082 (0.03%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Vaginal laceration * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Vulvovaginal discomfort * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Asphyxia * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Asthma * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Neonatal asphyxia * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Pneumomediastinum * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Pulmonary embolism * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Skin and subcutaneous tissue disorders           
Cutaneous vasculitis * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Dermatitis contact * 1  0/6082 (0.00%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Vascular disorders           
Deep vein thrombosis * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Hypertension * 1  1/6082 (0.02%)  1/6075 (0.02%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Thrombophlebitis * 1  1/6082 (0.02%)  0/6075 (0.00%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
1
Term from vocabulary, MedDRA 11.0
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Base Study Group 1: qHPV Vaccine Base Study Group 2: Placebo Base Study EXT LTFU: Cohort 1 LTFU: Cohort 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   551/6082 (9.06%)   499/6075 (8.21%)   0/594 (0.00%)   0/2448 (0.00%)   0/1888 (0.00%) 
General disorders           
Injection site erythema * 1  142/6082 (2.33%)  120/6075 (1.98%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Injection site pain * 1  503/6082 (8.27%)  433/6075 (7.13%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Injection site swelling * 1  97/6082 (1.59%)  76/6075 (1.25%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
Nervous system disorders           
Headache * 1  162/6082 (2.66%)  167/6075 (2.75%)  0/594 (0.00%)  0/2448 (0.00%)  0/1888 (0.00%) 
1
Term from vocabulary, MedDRA 11.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Executive Vice President, Clinical and Quantitative Sciences
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00092534    
Other Study ID Numbers: V501-015
2004_082
V501-015 ( Other Identifier: Merck )
First Submitted: September 23, 2004
First Posted: September 28, 2004
Results First Submitted: July 20, 2009
Results First Posted: November 26, 2009
Last Update Posted: March 4, 2020