Dose-Ranging Study of Quadrivalent Human Papillomavirus (HPV) (Types 6,11,16,18) L1 Virus-Like Particle (VLP) Vaccine (V501-007)(COMPLETED)
Official Title
A Placebo-Controlled, Dose-Ranging Study of Quadrivalent HPV Virus-Like Particle (VLP) Vaccine in 16- to 23-Year-Old Women
Acronym
Not provided
Organization
Merck Sharp & Dohme LLCINDUSTRY
Status Module
Record Verification Date
Oct 2015
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
May 2000
Primary Completion Date
May 2004Actual
Completion Date
Sep 2009Actual
First Submitted Date
Aug 16, 2006
First Submission Date that Met QC Criteria
Aug 16, 2006
First Posted Date
Aug 17, 2006Estimated
Results Waived
Not provided
Results First Submitted Date
May 19, 2010
Results First Submitted that Met QC Criteria
Jul 6, 2010
Results First Posted Date
Aug 3, 2010Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 6, 2015
Last Update Posted Date
Oct 7, 2015Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Merck Sharp & Dohme LLCINDUSTRY
Collaborators
Not provided
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
This study was conducted in 2 parts. Part A was a randomized, double-blind, placebo-controlled, multicenter, sequential dose-escalating evaluation. Part B was a randomized, double-blind (operating under in-house blinding procedures), placebo-controlled, multicenter, dose-ranging study.
Detailed Description
Not provided
Conditions Module
Conditions
Papillomavirus Infections
Genital Diseases, Female
Keywords
HPV 6/11/16/18 infection and related genital disease
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 1 received a 20/40/40/20 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 2 received a 40/40/40/40 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 3 received a 80/80/40/80 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 4 received placebo containing 225 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
20/40/40/20 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Number of Subjects With Injection Site Adverse Experiences
Days 1-5 following any vaccination visit
Secondary Outcomes
Measure
Description
Time Frame
Incidence of HPV 6-, 11-, 16- or 18-related Persistent Infection or Disease (Cervical Intraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia, Vaginal Intraepithelial Neoplasia, Adenocarcinoma in Situ, Cervical Cancer, and Genital Warts)
Through 36 Months
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Healthy females 16 to 23 years of age
Not pregnant at enrollment and must have agreed to use effective contraception through Month 7 of the study
Lifetime history of 0 to 4 male sexual partners (individuals with whom penetrative sexual intercourse occurred)
Exclusion Criteria:
No prior receipt of an Human Papillomavirus (HPV) vaccine
No receipt of inactivated or recombinant vaccines within 14 days prior to enrollment or receipt of live vaccines within 21 days prior to enrollment
No prior abnormal Pap test showing squamous intraepithelial lesion (SIL) or biopsy showing cervical intraepithelial neoplasia (CIN)
No prior history of genital warts or treatment for genital warts
Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR, Wheeler CM, Koutsky LA, Malm C, Lehtinen M, Skjeldestad FE, Olsson SE, Steinwall M, Brown DR, Kurman RJ, Ronnett BM, Stoler MH, Ferenczy A, Harper DM, Tamms GM, Yu J, Lupinacci L, Railkar R, Taddeo FJ, Jansen KU, Esser MT, Sings HL, Saah AJ, Barr E. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol. 2005 May;6(5):271-8. doi: 10.1016/S1470-2045(05)70101-7.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 1 received a 20/40/40/20 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
Periods
Title
Milestones
Reasons Not Completed
Base Study (Day 1 to Month 7)
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Prevention
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Biological: Placebo (mcg) (Aluminum Adjuvant)225
Placebo (mcg) (Aluminum Adjuvant) 450
Experimental
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 5 received placebo containing 450 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
40/40/40/40 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
80/80/40/80 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
placebo containing 225 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
Placebo (mcg) (Aluminum Adjuvant) 225
Placebo (mcg) (Aluminum Adjuvant) 450
Biological
placebo containing 450 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
Placebo (mcg) (Aluminum Adjuvant) 450
Background
Villa LL, Ault KA, Giuliano AR, Costa RL, Petta CA, Andrade RP, Brown DR, Ferenczy A, Harper DM, Koutsky LA, Kurman RJ, Lehtinen M, Malm C, Olsson SE, Ronnett BM, Skjeldestad FE, Steinwall M, Stoler MH, Wheeler CM, Taddeo FJ, Yu J, Lupinacci L, Railkar R, Marchese R, Esser MT, Bryan J, Jansen KU, Sings HL, Tamms GM, Saah AJ, Barr E. Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18. Vaccine. 2006 Jul 7;24(27-28):5571-83. doi: 10.1016/j.vaccine.2006.04.068. Epub 2006 May 15.
Villa LL, Costa RL, Petta CA, Andrade RP, Paavonen J, Iversen OE, Olsson SE, Hoye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, Krogh Gv, Lehtinen M, Malm C, Tamms GM, Giacoletti K, Lupinacci L, Railkar R, Taddeo FJ, Bryan J, Esser MT, Sings HL, Saah AJ, Barr E. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer. 2006 Dec 4;95(11):1459-66. doi: 10.1038/sj.bjc.6603469. Epub 2006 Nov 21.
Barr E, Gause CK, Bautista OM, Railkar RA, Lupinacci LC, Insinga RP, Sings HL, Haupt RM. Impact of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle vaccine in a sexually active population of North American women. Am J Obstet Gynecol. 2008 Mar;198(3):261.e1-11. doi: 10.1016/j.ajog.2007.09.001.
Joura EA, Leodolter S, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Garland SM, Harper DM, Tang GW, Ferris DG, Steben M, Jones RW, Bryan J, Taddeo FJ, Bautista OM, Esser MT, Sings HL, Nelson M, Boslego JW, Sattler C, Barr E, Paavonen J. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials. Lancet. 2007 May 19;369(9574):1693-702. doi: 10.1016/S0140-6736(07)60777-6.
Perez G, Lazcano-Ponce E, Hernandez-Avila M, Garcia PJ, Munoz N, Villa LL, Bryan J, Taddeo FJ, Lu S, Esser MT, Vuocolo S, Sattler C, Barr E. Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like-particle vaccine in Latin American women. Int J Cancer. 2008 Mar 15;122(6):1311-8. doi: 10.1002/ijc.23260.
Olsson SE, Villa LL, Costa RL, Petta CA, Andrade RP, Malm C, Iversen OE, Hoye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, von Krogh G, Lehtinen M, Paavonen J, Tamms GM, Giacoletti K, Lupinacci L, Esser MT, Vuocolo SC, Saah AJ, Barr E. Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine. Vaccine. 2007 Jun 21;25(26):4931-9. doi: 10.1016/j.vaccine.2007.03.049. Epub 2007 Apr 20.
Smith JF, Brownlow M, Brown M, Kowalski R, Esser MT, Ruiz W, Barr E, Brown DR, Bryan JT. Antibodies from women immunized with Gardasil cross-neutralize HPV 45 pseudovirions. Hum Vaccin. 2007 Jul-Aug;3(4):109-15. doi: 10.4161/hv.3.4.4058. Epub 2007 Feb 24.
Ault KA; Future II Study Group. Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials. Lancet. 2007 Jun 2;369(9576):1861-1868. doi: 10.1016/S0140-6736(07)60852-6.
Bergman H, Henschke N, Arevalo-Rodriguez I, Buckley BS, Crosbie EJ, Davies JC, Dwan K, Golder SP, Loke YK, Probyn K, Petkovic J, Villanueva G, Morrison J. Human papillomavirus (HPV) vaccination for the prevention of cervical cancer and other HPV-related diseases: a network meta-analysis. Cochrane Database Syst Rev. 2025 Nov 24;11(11):CD015364. doi: 10.1002/14651858.CD015364.pub2.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 2 received a 40/40/40/40 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 3 received a 80/80/40/80 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
FG003
Placebo (mcg) (Aluminum Adjuvant) 225
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 4 received placebo containing 225 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
FG004
Placebo (mcg) (Aluminum Adjuvant) 450
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 5 received placebo containing 450 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
FG005
Extension 1
This group includes 241 international subjects, who either: (1) received placebo during the base study and continued in the Extension to receive a dose of GARDASIL (20/40/40/20 mcg formulation of qHPV vaccine) at Month 60 (plus 2 and 3 at Months 62 and 66, respectively, (2) received 3 doses of GARDASIL during the Base study and continued into the Extension to receive a fourth dose of GARDASIL at Month 60 for the purposes of investigating whether a fourth dose of vaccine (administered ~4.5 years following completion of a 3-dose primary regimen) induces HPV 6, 11, 16, and 18 antibody responses that characterize immune therapy.
FG006
Extension 2
This group includes 17 subjects from the United States, who received placebo during the base study and received 3 doses of qHPV vaccine during the Extension, or received less than 3 doses of the qHPV Vaccine during the base study and completed the dose regimen during the Extension.
FG000290 subjects
FG001284 subjects
FG002292 subjects
FG003146 subjects
FG004146 subjects
FG0050 subjects
FG0060 subjects
COMPLETED
FG000269 subjects
FG001260 subjects
FG002271 subjects
FG003136 subjects
FG004139 subjects
FG0050 subjects
FG0060 subjects
NOT COMPLETED
FG00021 subjects
FG00124 subjects
FG00221 subjects
FG00310 subjects
FG0047 subjects
FG0050 subjects
FG0060 subjects
Type
Comment
Reasons
Randomized Not Vaccinated
FG0001 subjects
FG0012 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Adverse Event
FG0000 subjects
FG0012 subjects
FG0020 subjects
FG0030 subjects
FG004
Lost to Follow-up
FG0004 subjects
FG0016 subjects
FG0026 subjects
FG0034 subjects
FG004
Other
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Pregnancy
FG0003 subjects
FG0012 subjects
FG0023 subjects
FG0031 subjects
FG004
Protocol Violation
FG0001 subjects
FG0012 subjects
FG0020 subjects
FG0031 subjects
FG004
Withdrawal by Subject
FG00012 subjects
FG0019 subjects
FG00212 subjects
FG0034 subjects
FG004
Long Term Follow-up (Month 7 toMonth 36)
Type
Comment
Milestone Data
STARTED
FG000269 subjects
FG001260 subjects
FG002271 subjects
FG003136 subjects
FG004139 subjects
FG0050 subjects
FG0060 subjects
COMPLETED
FG000137 subjects
FG001245 subjects
FG002251 subjects
FG00357 subjects
FG004
NOT COMPLETED
FG000132 subjects
FG00115 subjects
FG00220 subjects
FG00379 subjects
FG004
Type
Comment
Reasons
Proceeded to Extension 1
FG000114 subjects
FG0010 subjects
FG0020 subjects
FG003
Extension 1
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG005241 subjects
FG0060 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Extension 2
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG00617 subjects17 Participants continued into Extension 2 from Extension 1
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 1 received a 20/40/40/20 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 2 received a 40/40/40/40 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 3 received a 80/80/40/80 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
BG003
Placebo (mcg) (Aluminum Adjuvant) 225
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 4 received placebo containing 225 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
BG004
Placebo (mcg) (Aluminum Adjuvant) 450
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 5 received placebo containing 450 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000290
BG001284
BG002292
BG003146
BG004146
BG0051158
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Full Range
years
Title
Denominators
Categories
Title
Measurements
BG00020.2(16 to 23)
BG00120.0(15 to 24)
BG00220.1(16 to 23)
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG000290
BG001284
BG002
Race/Ethnicity, Customized
Number
participants
Title
Denominators
Categories
Asian
Title
Measurements
BG0007
BG00111
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Number of Subjects With Injection Site Adverse Experiences
All vaccinated subjects with adverse experience follow-up.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 1 received a 20/40/40/20 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 2 received a 40/40/40/40 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 3 received a 80/80/40/80 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
OG003
Placebo (mcg) (Aluminum Adjuvant) 225
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 4 received placebo containing 225 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
OG004
Placebo (mcg) (Aluminum Adjuvant) 450
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 5 received placebo containing 450 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
Units
Counts
Participants
OG000288
OG001282
OG002292
OG003
Title
Denominators
Categories
Title
Measurements
OG000247
OG001248
OG002266
OG003
Secondary
Incidence of HPV 6-, 11-, 16- or 18-related Persistent Infection or Disease (Cervical Intraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia, Vaginal Intraepithelial Neoplasia, Adenocarcinoma in Situ, Cervical Cancer, and Genital Warts)
Per-protocol population: subjects must have no major protocol violations, must be seronegative at Day 1 and PCR negative through Month 7 to the relevant HPV type, and must provide follow-up data after Month 7
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 1 received a 20/40/40/20 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
OG001
Placebo (mcg) (Aluminum Adjuvant) 225 or 450 Combined
For the purposes of this outcome measure, the placebo groups (225 mcg and 450 mcg) were combined.
Units
Time Frame
Adverse events (AEs) were collected from Day 1 until Month 7. AEs were collected on the subject's vaccination report card daily for 14 days after each injection.
Description
Subjects were observed for 30 minutes after each vaccination. Temperatures were recorded for 5 days after each injection (4 hours after injection and daily for the next 4 days). At Months 2, 3, 6, and 7, subjects were solicited for any gynecological health concerns and any SAEs that had occurred.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 1 received a 20/40/40/20 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
There was one subject randomized to the quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP vaccine 20/40/40/20 mcg group who received the 225 mcg aluminum adjuvant placebo at the third vaccination visit. This subject was not included in the counts reported in the Adverse Event tables. No SAEs were reported for this subject.
There was 1 patient that was randomized, but never vaccinated. As such, that patient is not included in this table.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 2 received a 40/40/40/40 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
There were 2 patients from the 40/40/40/40 group that were randomized, but were never vaccinated. As such, these 2 patients are not included in this table.
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 3 received a 80/80/40/80 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
2
292
263
292
EG003
Placebo (mcg) (Aluminum Adjuvant) 225
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 4 received placebo containing 225 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
0
146
105
146
EG004
Placebo (mcg) (Aluminum Adjuvant) 450
The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 5 received placebo containing 450 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36.
3
146
114
146
EG005
Extensions
This group includes 241 international subjects, who either: (1) received placebo during the base study and continued in the Extension to receive a dose of GARDASIL (20/40/40/20 mcg formulation of qHPV vaccine) at Month 60 (plus 2 and 3 at Months 62 and 66, respectively, (2) received 3 doses of GARDASIL during the Base study and continued into the Extension to receive a fourth dose of GARDASIL at Month 60 for the purposes of investigating whether a fourth dose of vaccine (administered ~4.5 years following completion of a 3-dose primary regimen) induces HPV 6, 11, 16, and 18 antibody responses that characterize immune therapy.
Serious Adverse Events (SAEs) were collected during Extension 1 and Extension 2. Note that the N includes only the 241 subjects vaccinated during the Extension Periods; of the 258 subjects that entered either Extension, 17 subjects discontinued before being vaccinated and therefore are not included in this table.
1
241
180
241
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Appendicitis
Gastrointestinal disorders
MedDRA 12.0
Systematic Assessment
EG0000 affected288 at risk
EG0010 affected282 at risk
EG0020 affected292 at risk
EG0030 affected146 at risk
EG0041 affected146 at risk
EG0050 affected241 at risk
Kidney infection
Gastrointestinal disorders
MedDRA 12.0
Systematic Assessment
EG0000 affected288 at risk
EG0010 affected282 at risk
EG0020 affected292 at risk
EG003
Pyelonephritis
Gastrointestinal disorders
MedDRA 12.0
Systematic Assessment
EG0000 affected288 at risk
EG0010 affected282 at risk
EG0021 affected292 at risk
EG003
Drug toxicity
Injury, poisoning and procedural complications
MedDRA 12.0
Systematic Assessment
EG0000 affected288 at risk
EG0010 affected282 at risk
EG0020 affected292 at risk
EG003
Pancreatic carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 12.0
Systematic Assessment
EG0001 affected288 at risk
EG0010 affected282 at risk
EG0020 affected292 at risk
EG003
Depression
Psychiatric disorders
MedDRA 12.0
Systematic Assessment
EG0001 affected288 at risk
EG0010 affected282 at risk
EG0021 affected292 at risk
EG003
Renal colic
Renal and urinary disorders
MedDRA 12.0
Systematic Assessment
EG0001 affected288 at risk
EG0010 affected282 at risk
EG0020 affected292 at risk
EG003
Cervix haemorrhage uterine
Reproductive system and breast disorders
MedDRA 12.0
Systematic Assessment
EG0000 affected288 at risk
EG0010 affected282 at risk
EG0020 affected292 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal pain
Gastrointestinal disorders
MedDRA 12.0
Systematic Assessment
EG00013 affected288 at risk
EG00114 affected282 at risk
EG00216 affected292 at risk
EG0035 affected146 at risk
EG0049 affected146 at risk
EG0050 affected241 at risk
Abdominal pain upper
Gastrointestinal disorders
MedDRA 12.0
Systematic Assessment
EG00010 affected288 at risk
EG00116 affected282 at risk
EG0028 affected292 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 12.0
Systematic Assessment
EG00019 affected288 at risk
EG00123 affected282 at risk
EG00221 affected292 at risk
EG003
Fatigue
General disorders
MedDRA 12.0
Systematic Assessment
EG00026 affected288 at risk
EG0018 affected282 at risk
EG00223 affected292 at risk
EG003
Pyrexia
General disorders
MedDRA 12.0
Systematic Assessment
EG00030 affected288 at risk
EG00137 affected282 at risk
EG00241 affected292 at risk
EG003
Injection Site Erythema
General disorders
MedDRA 12.0
Systematic Assessment
EG00075 affected288 at risk
EG00159 affected282 at risk
EG00280 affected292 at risk
EG003
Injection Site Haematoma
General disorders
MedDRA 12.0
Systematic Assessment
EG00017 affected288 at risk
EG0019 affected282 at risk
EG00214 affected292 at risk
EG003
Injection Site Pain
General disorders
MedDRA 12.0
Systematic Assessment
EG000245 affected288 at risk
EG001247 affected282 at risk
EG002263 affected292 at risk
EG003
Injection Site Swelling
General disorders
MedDRA 12.0
Systematic Assessment
EG00080 affected288 at risk
EG00174 affected282 at risk
EG00295 affected292 at risk
EG003
Influenza
Infections and infestations
MedDRA 12.0
Systematic Assessment
EG00013 affected288 at risk
EG00117 affected282 at risk
EG00215 affected292 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 12.0
Systematic Assessment
EG00020 affected288 at risk
EG00123 affected282 at risk
EG00220 affected292 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 12.0
Systematic Assessment
EG00012 affected288 at risk
EG00110 affected282 at risk
EG0028 affected292 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 12.0
Systematic Assessment
EG0009 affected288 at risk
EG0016 affected282 at risk
EG0024 affected292 at risk
EG003
Headache
Nervous system disorders
MedDRA 12.0
Systematic Assessment
EG000117 affected288 at risk
EG001103 affected282 at risk
EG002116 affected292 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA 12.0
Systematic Assessment
EG00010 affected288 at risk
EG0018 affected282 at risk
EG00213 affected292 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 12.0
Systematic Assessment
EG00020 affected288 at risk
EG00110 affected282 at risk
EG00217 affected292 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Point of Contact
Title
Organization
Phone
Extension
Email
Senior Vice President,Global Clinical Development
Merck Sharp & Dohme Corp.
1-800-672-6372
ClinicalTrialsDisclosure@merck.com
ID
Term
D030361
Papillomavirus Infections
D005831
Genital Diseases, Female
Ancestor Terms
ID
Term
D015229
Sexually Transmitted Diseases, Viral
D012749
Sexually Transmitted Diseases
D003141
Communicable Diseases
D007239
Infections
D004266
DNA Virus Infections
D014777
Virus Diseases
D014412
Tumor Virus Infections
D000091662
Genital Diseases
D000091642
Urogenital Diseases
D020969
Disease Attributes
D010335
Pathologic Processes
D013568
Pathological Conditions, Signs and Symptoms
D052776
Female Urogenital Diseases
D005261
Female Urogenital Diseases and Pregnancy Complications
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
D000068857
Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18
Ancestor Terms
ID
Term
D017778
Vaccines, Combined
D014612
Vaccines
D001688
Biological Products
D045424
Complex Mixtures
D053918
Papillomavirus Vaccines
D014765
Viral Vaccines
Browse Leaves
Not provided
Browse Branches
Not provided
1 subjects
FG0050 subjects
FG0060 subjects
0 subjects
FG0050 subjects
FG0060 subjects
0 subjects
FG0050 subjects
FG0060 subjects
1 subjects
FG0050 subjects
FG0060 subjects
2 subjects
FG0050 subjects
FG0060 subjects
3 subjects
FG0050 subjects
FG0060 subjects
57 subjects
FG0050 subjects
FG0060 subjects
82 subjects
FG0050 subjects
FG0060 subjects
69 subjects
FG00475 subjects
FG0050 subjects
FG0060 subjects
Lost to Follow-up
FG0006 subjects
FG0018 subjects
FG0025 subjects
FG0034 subjects
FG0043 subjects
FG0050 subjects
FG0060 subjects
Moved
FG0003 subjects
FG0012 subjects
FG0021 subjects
FG0032 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Other
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
FG0060 subjects
Protocol Violation
FG0000 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Withdrawal by Subject
FG0007 subjects
FG0014 subjects
FG00213 subjects
FG0034 subjects
FG0043 subjects
FG0050 subjects
FG0060 subjects
0 subjects
FG005219 subjects
FG0060 subjects
0 subjects
FG00522 subjects
FG0060 subjects
0 subjects
FG0040 subjects
FG0051 subjects
FG0060 subjects
Other
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0059 subjects
FG0060 subjects
Moved
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0054 subjects
FG0060 subjects
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0053 subjects
FG0060 subjects
Pregnancy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0054 subjects
FG0060 subjects
Protocol Violation
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0051 subjects
FG0060 subjects
0 subjects
FG0050 subjects
FG0067 subjects
0 subjects
FG0050 subjects
FG00610 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0062 subjects
Other
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0063 subjects
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0065 subjects
20.0
(16 to 23)
BG00420.1(13 to 23)
BG00520.0(13 to 24)
292
BG003146
BG004146
BG0051158
Male
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
5
BG0036
BG0045
BG00534
Black
Title
Measurements
BG00025
BG00132
BG00227
BG00312
BG0047
BG005103
Hispanic American
Title
Measurements
BG00015
BG00115
BG00210
BG00310
BG00411
BG00561
Indian
Title
Measurements
BG0000
BG0010
BG0022
BG0030
BG0040
BG0052
Multi-racial
Title
Measurements
BG00013
BG0019
BG0026
BG0037
BG0044
BG00539
Native American
Title
Measurements
BG0002
BG0014
BG0022
BG0030
BG0041
BG0059
White
Title
Measurements
BG000228
BG001213
BG002240
BG003111
BG004118
BG005910
146
OG004146
107
OG004115
Counts
Participants
OG000235
OG001233
Title
Denominators
Categories
Title
Measurements
OG0000.7
OG0016.7
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Vaccine Efficacy
89.5
95
70.7
97.3
Vaccine Efficacy (% relative risk reduction)
Confidence Interval based on binomial tail probabilities and not from a dispersion parameter.