Cervical CancerPhase 3NCT00543543

Broad Spectrum HPV (Human Papillomavirus) Vaccine Study in 16-to 26-Year-Old Women (V503-001)

A Phase 3 study testing Comparator: GARDASIL and Experimental: V503 in people with Cervical Cancer and Vulvar Cancer, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 16 to 26 years, women onlyHealthy volunteers can take part
Conditions the study is for: Cervical Cancer, Vulvar Cancer, Vaginal Cancer
What is being tested?: Comparator: GARDASIL and Experimental: V503
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14,840 participants
Where: No sites listed yet
Study dates: 24 Sep 2007to 7 Jul 2016
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 16 to 26 years
Women only
Healthy volunteers accepted
Child, Adult

Who may be able to join

Female between 16- to 26-years-old
Has never had Pap testing or has only had normal Pap (Papanicolaou) test results
For the immune memory substudy in the extension (Cohort 1): was randomized to V503 in the base study and was in the per-protocol immunogenicity population for ≥1 HPV type
For the 3-dose V503 vaccination substudy in the extension (Cohort 2): was randomized to GARDASIL in the base study and received ≥1 dose of GARDASIL

Who cannot join

History of an abnormal cervical biopsy result
History of a positive test for HPV
History of external genital/vaginal warts
Currently a user of any illegal drugs or an alcohol abuser
History of severe allergic reaction that required medical attention
Are pregnant

Show all 9Show fewer

Received marketed HPV vaccine or participated in an HPV trial
Currently enrolled in a clinical trial
Currently has or has a history of certain medical conditions or is currently taking or has taken certain medications (details will be discussed at the time of consent.)

About this study

Official title: A Randomized, International, Double-Blinded (With In-House Blinding), Controlled With GARDASIL, Dose-Ranging, Tolerability, Immunogenicity, and Efficacy Study of a Multivalent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine Administered to 16- to 26- Year-Old Women

The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of V503 in comparison to GARDASIL. The primary hypotheses tested in the study were 1) V503 administered to 16- to 26-year-old adolescents and young women is generally well-tolerated, 2) V503 reduces combined incidence of Human Papillomavirus (HPV) Type 31/33/45/52/58-related disease compared with GARDASIL, and 3) V503 induces non-inferior geometric mean titers for HPV Type 6/11/16/18 antibodies compared with GARDASIL.

Read the detailed description

The study included a dose-finding evaluation of a 3-dose regimen of V503 and GARDASIL, a safety/efficacy evaluation of a 3-dose regimen of the selected V503 dose formulation and GARDASIL, and an extension consisting of 2 substudies: an evaluation of immune memory in participants receiving a fourth vaccination with V503 (Cohort 1), and an opportunity for participants who received GARDASIL in the Base Study to receive a 3-dose regimen of V503 (Cohort 2).

Conditions: Cervical Cancer, Vulvar Cancer, Vaginal Cancer, Genital Warts, Human Papillomavirus Infection
Being tested: Comparator: GARDASIL, Experimental: V503
Medical subject headings: Uterine Cervical Neoplasms, Vulvar Neoplasms, Vaginal Neoplasms, Condylomata Acuminata, Papillomavirus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Comparator: GARDASILBiological
GARDASIL (quadrivalent HPV [Types 6, 11, 16, and 18] L1 virus-like particle vaccine), 0.5 mL injection in 3 dose regimen
Experimental: V503Biological
V503 (9-valent HPV [Types 6, 11, 16, 18, 31, 33, 45, 52, and 58] L1 virus-like particle vaccine), 0.5 mL injection in 3 dose regimen (and a fourth injection for Cohort 1 only).

Study groups in NCT00543543
Study group	Role	What they receive
Low-dose V503	Experimental	V503 (9-Valent Human Papillomavirus [HPV] Vaccine) low-dose 0.5 mL injection in a 3-dose regimen in the base study. Receives: Biological: Experimental: V503
Mid-dose V503	Experimental	V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study. Receives: Biological: Experimental: V503
High-dose V503	Experimental	V503 (9-Valent HPV Vaccine) high-dose 0.5 mL injection in a 3-dose regimen in the base study. Receives: Biological: Experimental: V503
Gardasil	Active comparator	Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study. Receives: Biological: Comparator: GARDASIL; Biological: Experimental: V503

What is being measured

The primary outcome is the main question the study is designed to answer.

Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Disease (Test of Hypothesis)
HPV Type 31/33/45/52/58-related high-grade Cervical Intraepithelial Neoplasia (CIN 2/3), Adenocarcinoma in Situ (AIS), Invasive Cervical Carcinoma, high-grade Vulvar Intraepithelial Neoplasia (VIN 2/3), high-grade Vaginal Intraepithelial Neoplasia (VaIN 2/3), vulvar cancer, or vaginal cancer were determined by clinical/pathologic criteria and positive Polymerase Chain Reaction (PCR) assay for virus subtype. This outcome measure reports data based on the protocol-specified plan of conducting hypothesis testing when at least 30 cases had accumulated. The cutoff date for this analysis was 10 April 2013. Disease incidence was defined as the number of primary efficacy cases per 10,000 person-years of follow-up in a treatment arm.
Measured: From Day 1 until >=30 cases accumulate, up to Month 54 in the base study
Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Disease (End-of-study Update)
HPV Type 31/33/45/52/58-related high-grade Cervical Intraepithelial Neoplasia (CIN 2/3), Adenocarcinoma in Situ (AIS), Invasive Cervical Carcinoma, high-grade Vulvar Intraepithelial Neoplasia (VIN 2/3), high-grade Vaginal Intraepithelial Neoplasia (VaIN 2/3), vulvar cancer, or vaginal cancer were determined by clinical/pathologic criteria and positive Polymerase Chain Reaction (PCR) assay for virus subtype. This outcome measure reports cumulative study data through 10 March 2014. Disease incidence was defined as the number of primary efficacy cases per 10,000 person-years of follow-up in a treatment arm.
Measured: Up to Month 54 in the base study
Base Study: Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18/31/33/45/52/58
Serum antibodies to HPV types 6/11/16/18/31/33/45/52/58 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL. Statistical analysis was performed only for HPV types contained in both vaccines.
Measured: 4 weeks postdose 3 in the base study
Base Study: Percentage of Participants With One or More Adverse Event
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE.
Measured: Up to Month 7 (low- and high-dose V503) or up to Month 54 (mid-dose V503 and Gardasil)
Base Study: Percentage of Participants With One or More Injection-site Adverse Event
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site were recorded.
Measured: Up to Day 5 after any vaccination
Base Study: Percentage of Participants With One or More Non-injection-site (Systemic) Adverse Event
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Systemic AEs were those not categorized as injection-site AEs.
Measured: Up to Day 15 after any vaccination
Base Study: Percentage of Participants With One or More Vaccine-related Adverse Event
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. An AE that is judged by the investigator to be "definitely related," "probably related," or "possibly related" to the study drug is defined as a vaccine-related AE.
Measured: Up to Month 7 (low- and high-dose V503) or up to Month 54 (mid-dose V503 and Gardasil)
Base Study: Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event
An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse event.
Measured: Up to Month 6

Secondary outcomes (2)

Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Persistent Infection
Combined Incidence of HPV Type 31/33/45/52/58-related persistent infection as determined by clinical/pathologic criteria and positive Polymerase Chain Reaction (PCR) assay for virus subtype. Persistent infection was defined as infection detected in samples from >=2 consecutive visits 6 months (+/-1 month visit window) or longer apart. Incidence was defined as the number of cases of persistent infection per 10,000 person-years of follow-up in a treatment arm.
Measured: Up to Month 54 in the base study
Base Study: Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58
Serum antibodies to HPV types were measured with a Competitive Luminex Immunoassay. The serostatus cutoffs (milli Merck U/mL) for HPV types were as follows: HPV Type 6: ≥30; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24; HPV Type 31: ≥10; HPV Types 33, 45, 52, and 58: ≥8.
Measured: 4 weeks postdose 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Sep 20077 Jul 2016

First posted15 Oct 2007 (estimated)
Study start24 Sep 2007
Primary completion10 Apr 2013
Study completion7 Jul 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (14)Papers the sponsor has linked to this study.
Other trials for Cervical CancerStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 14,840 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00543543
Sponsor's protocol ID: V503-001
Other IDs: 2007_538
Status last verified: Oct 2018
First submitted: 12 Oct 2007
Last updated: 27 Nov 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Luxembourg A, Brown D, Bouchard C, Giuliano AR, Iversen OE, Joura EA, Penny ME, Restrepo JA, Romaguera J, Maansson R, Moeller E, Ritter M, Chen J. Phase II studies to select the formulation of a multivalent HPV L1 virus-like particle (VLP) vaccine. Hum Vaccin Immunother. 2015;11(6):1313-22. doi: 10.1080/21645515.2015.1012010.
PubMed 25912208
Joura EA, Giuliano AR, Iversen OE, Bouchard C, Mao C, Mehlsen J, Moreira ED Jr, Ngan Y, Petersen LK, Lazcano-Ponce E, Pitisuttithum P, Restrepo JA, Stuart G, Woelber L, Yang YC, Cuzick J, Garland SM, Huh W, Kjaer SK, Bautista OM, Chan IS, Chen J, Gesser R, Moeller E, Ritter M, Vuocolo S, Luxembourg A; Broad Spectrum HPV Vaccine Study. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015 Feb 19;372(8):711-23. doi: 10.1056/NEJMoa1405044.
PubMed 25693011
Chen YH, Gesser R, Luxembourg A. A seamless phase IIB/III adaptive outcome trial: design rationale and implementation challenges. Clin Trials. 2015 Feb;12(1):84-90. doi: 10.1177/1740774514552110. Epub 2014 Oct 1.
PubMed 25278227
Luxembourg A, Bautista O, Moeller E, Ritter M, Chen J. Design of a large outcome trial for a multivalent human papillomavirus L1 virus-like particle vaccine. Contemp Clin Trials. 2015 May;42:18-25. doi: 10.1016/j.cct.2015.02.009. Epub 2015 Mar 3.
PubMed 25749310
Pitisuttithum P, Velicer C, Luxembourg A. 9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV. Expert Rev Vaccines. 2015;14(11):1405-19. doi: 10.1586/14760584.2015.1089174. Epub 2015 Sep 14.
PubMed 26366475
Moreira ED Jr, Block SL, Ferris D, Giuliano AR, Iversen OE, Joura EA, Kosalaraksa P, Schilling A, Van Damme P, Bornstein J, Bosch FX, Pils S, Cuzick J, Garland SM, Huh W, Kjaer SK, Qi H, Hyatt D, Martin J, Moeller E, Ritter M, Baudin M, Luxembourg A. Safety Profile of the 9-Valent HPV Vaccine: A Combined Analysis of 7 Phase III Clinical Trials. Pediatrics. 2016 Aug;138(2):e20154387. doi: 10.1542/peds.2015-4387. Epub 2016 Jul 15.
PubMed 27422279
Huh WK, Joura EA, Giuliano AR, Iversen OE, de Andrade RP, Ault KA, Bartholomew D, Cestero RM, Fedrizzi EN, Hirschberg AL, Mayrand MH, Ruiz-Sternberg AM, Stapleton JT, Wiley DJ, Ferenczy A, Kurman R, Ronnett BM, Stoler MH, Cuzick J, Garland SM, Kjaer SK, Bautista OM, Haupt R, Moeller E, Ritter M, Roberts CC, Shields C, Luxembourg A. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial. Lancet. 2017 Nov 11;390(10108):2143-2159. doi: 10.1016/S0140-6736(17)31821-4. Epub 2017 Sep 5.
PubMed 28886907
Joura E, Kjaer SK, Bautista O, Luxembourg A, Saah A, Giuliano A. Effect of Prior 9-Valent Human Papillomavirus Vaccination on Subsequent Lower Genital Tract Dysplasia After Cervical Excisional Surgery. Obstet Gynecol. 2026 Jan 1;147(1):73-82. doi: 10.1097/AOG.0000000000006113. Epub 2025 Oct 30.
PubMed 41166720
Kjaer SK, Nygard M, Sundstrom K, Munk C, Berger S, Dzabic M, Fridrich KE, Waldstrom M, Sorbye SW, Bautista O, Group T, Luxembourg A. Long-term effectiveness of the nine-valent human papillomavirus vaccine in Scandinavian women: interim analysis after 8 years of follow-up. Hum Vaccin Immunother. 2021 Apr 3;17(4):943-949. doi: 10.1080/21645515.2020.1839292. Epub 2020 Dec 16.
PubMed 33326342
Giuliano AR, Joura EA, Garland SM, Huh WK, Iversen OE, Kjaer SK, Ferenczy A, Kurman RJ, Ronnett BM, Stoler MH, Bautista OM, Moeller E, Ritter M, Shields C, Luxembourg A. Nine-valent HPV vaccine efficacy against related diseases and definitive therapy: comparison with historic placebo population. Gynecol Oncol. 2019 Jul;154(1):110-117. doi: 10.1016/j.ygyno.2019.03.253. Epub 2019 Apr 11.
PubMed 30982556
Garland SM, Pitisuttithum P, Ngan HYS, Cho CH, Lee CY, Chen CA, Yang YC, Chu TY, Twu NF, Samakoses R, Takeuchi Y, Cheung TH, Kim SC, Huang LM, Kim BG, Kim YT, Kim KH, Song YS, Lalwani S, Kang JH, Sakamoto M, Ryu HS, Bhatla N, Yoshikawa H, Ellison MC, Han SR, Moeller E, Murata S, Ritter M, Sawata M, Shields C, Walia A, Perez G, Luxembourg A. Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries. J Infect Dis. 2018 Jun 5;218(1):95-108. doi: 10.1093/infdis/jiy133.
PubMed 29767739
Ruiz-Sternberg AM, Moreira ED Jr, Restrepo JA, Lazcano-Ponce E, Cabello R, Silva A, Andrade R, Revollo F, Uscanga S, Victoria A, Guevara AM, Luna J, Plata M, Dominguez CN, Fedrizzi E, Suarez E, Reina JC, Ellison MC, Moeller E, Ritter M, Shields C, Cashat M, Perez G, Luxembourg A. Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women. Papillomavirus Res. 2018 Jun;5:63-74. doi: 10.1016/j.pvr.2017.12.004. Epub 2017 Dec 19.
PubMed 29269325
Moreira ED, Giuliano AR, de Hoon J, Iversen OE, Joura EA, Restrepo J, Van Damme P, Vandermeulen C, Ellison MC, Krick A, Shields C, Heiles B, Luxembourg A. Safety profile of the 9-valent human papillomavirus vaccine: assessment in prior quadrivalent HPV vaccine recipients and in men 16 to 26 years of age. Hum Vaccin Immunother. 2018 Feb 1;14(2):396-403. doi: 10.1080/21645515.2017.1403700. Epub 2017 Dec 14.
PubMed 29211620
Guevara A, Cabello R, Woelber L, Moreira ED Jr, Joura E, Reich O, Shields C, Ellison MC, Joshi A, Luxembourg A. Antibody persistence and evidence of immune memory at 5years following administration of the 9-valent HPV vaccine. Vaccine. 2017 Sep 5;35(37):5050-5057. doi: 10.1016/j.vaccine.2017.07.017. Epub 2017 Aug 5.
PubMed 28789851

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 27 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, International, Double-Blinded (With In-House Blinding), Controlled With GARDASIL, Dose-Ranging, Tolerability, Immunogenicity, and Efficacy Study of a Multivalent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine Administered to 16- to 26- Year-Old Women
ClinicalTrials.gov ID: NCT00543543
Acronym / sponsor ID: V503-001
Conditions: Cervical Cancer, Vulvar Cancer, Vaginal Cancer, Genital Warts, Human Papillomavirus Infection
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 14,840 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 24 Sep 2007 (actual)
Primary completion: 10 Apr 2013 (actual)
Study completion: 7 Jul 2016 (actual)
First posted: 15 Oct 2007 (estimated)
Results: Posted 19 Dec 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Low-dose V503	Experimental	Biological: Experimental: V503V503 (9-Valent Human Papillomavirus [HPV] Vaccine) low-dose 0.5 mL injection in a 3-dose regimen in the base study.
Mid-dose V503	Experimental	Biological: Experimental: V503V503 (9-Valent HPV Vaccine) mid-dose 0.5 mL injection in a 3-dose regimen in the base study. A subset of participants (Cohort 1) received a fourth V503 mid-dose vaccination in the extension study.
High-dose V503	Experimental	Biological: Experimental: V503V503 (9-Valent HPV Vaccine) high-dose 0.5 mL injection in a 3-dose regimen in the base study.
Gardasil	Active comparator	Biological: Comparator: GARDASIL, Biological: Experimental: V503Gardasil (4-Valent HPV Vaccine) 0.5 mL injection in a 3-dose regimen in the base study. Participants (Cohort 2) were offered the V503 mid-dose 3-dose regimen in the extension study.

Who may qualify

Ages: 16 to 26 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (4 listed)

Female between 16- to 26-years-old
Has never had Pap testing or has only had normal Pap (Papanicolaou) test results
For the immune memory substudy in the extension (Cohort 1): was randomized to V503 in the base study and was in the per-protocol immunogenicity population for ≥1 HPV type
For the 3-dose V503 vaccination substudy in the extension (Cohort 2): was randomized to GARDASIL in the base study and received ≥1 dose of GARDASIL

Key exclusion criteria (9 listed)

History of an abnormal cervical biopsy result
History of a positive test for HPV
History of external genital/vaginal warts
Currently a user of any illegal drugs or an alcohol abuser
History of severe allergic reaction that required medical attention

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Comparator: GARDASILGARDASIL (quadrivalent HPV [Types 6, 11, 16, and 18] L1 virus-like particle vaccine), 0.5 mL injection in 3 dose regimen	Biological	Gardasil
Experimental: V503V503 (9-valent HPV [Types 6, 11, 16, 18, 31, 33, 45, 52, and 58] L1 virus-like particle vaccine), 0.5 mL injection in 3 dose regimen (and a fourth injection for Cohort 1 only).	Biological	Gardasil, High-dose V503, Low-dose V503, Mid-dose V503

Primary outcome

Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Disease (Test of Hypothesis)
Time frame: From Day 1 until >=30 cases accumulate, up to Month 54 in the base study
HPV Type 31/33/45/52/58-related high-grade Cervical Intraepithelial Neoplasia (CIN 2/3), Adenocarcinoma in Situ (AIS), Invasive Cervical Carcinoma, high-grade Vulvar Intraepithelial Neoplasia (VIN 2/3), high-grade Vaginal Intraepithelial Neoplasia (VaIN 2/3), vulvar cancer, or vaginal cancer were determined by clinical/pathologic criteria and positive Polymerase Chain Reaction (PCR) assay for virus subtype. This outcome measure reports data based on the protocol-specified plan of conducting hypothesis testing when at least 30 cases had accumulated. The cutoff date for this analysis was 10 April 2013. Disease incidence was defined as the number of primary efficacy cases per 10,000 person-years of follow-up in a treatment arm.
Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Disease (End-of-study Update)
Time frame: Up to Month 54 in the base study
HPV Type 31/33/45/52/58-related high-grade Cervical Intraepithelial Neoplasia (CIN 2/3), Adenocarcinoma in Situ (AIS), Invasive Cervical Carcinoma, high-grade Vulvar Intraepithelial Neoplasia (VIN 2/3), high-grade Vaginal Intraepithelial Neoplasia (VaIN 2/3), vulvar cancer, or vaginal cancer were determined by clinical/pathologic criteria and positive Polymerase Chain Reaction (PCR) assay for virus subtype. This outcome measure reports cumulative study data through 10 March 2014. Disease incidence was defined as the number of primary efficacy cases per 10,000 person-years of follow-up in a treatment arm.
Base Study: Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18/31/33/45/52/58
Time frame: 4 weeks postdose 3 in the base study
Serum antibodies to HPV types 6/11/16/18/31/33/45/52/58 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL. Statistical analysis was performed only for HPV types contained in both vaccines.
Base Study: Percentage of Participants With One or More Adverse Event
Time frame: Up to Month 7 (low- and high-dose V503) or up to Month 54 (mid-dose V503 and Gardasil)
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE.
Base Study: Percentage of Participants With One or More Injection-site Adverse Event
Time frame: Up to Day 5 after any vaccination
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site were recorded.
Base Study: Percentage of Participants With One or More Non-injection-site (Systemic) Adverse Event
Time frame: Up to Day 15 after any vaccination
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Systemic AEs were those not categorized as injection-site AEs.
Base Study: Percentage of Participants With One or More Vaccine-related Adverse Event
Time frame: Up to Month 7 (low- and high-dose V503) or up to Month 54 (mid-dose V503 and Gardasil)
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. An AE that is judged by the investigator to be "definitely related," "probably related," or "possibly related" to the study drug is defined as a vaccine-related AE.
Base Study: Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event
Time frame: Up to Month 6
An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse event.

2 secondary outcomes

Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Persistent Infection
Time frame: Up to Month 54 in the base study
Base Study: Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58
Time frame: 4 weeks postdose 3

Results and safety

Results posted to the registry on 19 Dec 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Low-dose V503	315	295
Mid-dose V503	7,106	5,854
High-dose V503	310	296
Gardasil	7,109	5,887

Primary outcome: Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Disease (Test of Hypothesis)

Time frame: From Day 1 until >=30 cases accumulate, up to Month 54 in the base study. Number. Unit: Cases per 10,000 person-years follow-up

Measure	Mid-dose V503 n = 6016	Gardasil n = 6017
Value	0.5	15.8

Mid-dose V503 vs Gardasil: Vaccine efficacy: 96.7 (95% CI 80.9 to 99.8), p <0.0001, Exact test, 1-sided

Population analysed: The Per-protocol Efficacy population included all participants who received all 3 vaccinations of mid-dose V503 or Gardasil within acceptable day ranges, were seronegative at Day 1 and PCR negative at Day 1 through Day 7 to the relevant HPV types, and had at least 1 follow-up visit following Month 7.

Primary outcome: Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Disease (End-of-study Update)

Time frame: Up to Month 54 in the base study. Number. Unit: Cases per 10,000 person-years follow-up

Measure	Mid-dose V503 n = 6016	Gardasil n = 6017
Value	0.5	19.0

Mid-dose V503 vs Gardasil: Vaccine efficacy: 97.4 (95% CI 85.0 to 99.9), Exact test, 1-sided

Primary outcome: Base Study: Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18/31/33/45/52/58

Time frame: 4 weeks postdose 3 in the base study. Geometric mean (95% Confidence Interval). Unit: milli Merck U/mL

Measure	Mid-dose V503 n = 6792	Gardasil n = 6795
Anti-HPV Type 6 (n=3993, 3975)	893.1 (871.7 to 915.1)	875.2 (854.2 to 896.8)
Anti-HPV Type 11 (n=3995, 3982)	666.3 (649.6 to 683.4)	830.0 (809.2 to 851.4)
Anti-HPV Type 16 (n=4032, 4062)	3131.1 (3057.1 to 3206.9)	3156.6 (3082.3 to 3232.7)
Anti-HPV Type 18 (n=4539, 4541)	804.6 (782.7 to 827.1)	678.7 (660.2 to 697.7)
Anti-HPV Type 31 (n=4466, 4377)	658.4 (636.7 to 680.9)	9.7 (9.4 to 10.1)
Anti-HPV Type 33 (n=4702, 4691)	415.9 (405.6 to 426.4)	NA (NA to NA)
Anti-HPV Type 45 (n=4792, 4750)	252.8 (246.2 to 259.6)	NA (NA to NA)
Anti-HPV Type 52 (n=4455, 4335)	379.7 (371.6 to 388.0)	NA (NA to NA)

Mid-dose V503 vs Gardasil: GMT ratio: 1.02 (95% CI 0.99 to 1.06), p <0.001, ANOVA
Mid-dose V503 vs Gardasil: GMT ratio: 0.80 (95% CI 0.77 to 0.83), p <0.001, ANOVA
Mid-dose V503 vs Gardasil: GMT ratio: 0.99 (95% CI 0.96 to 1.03), p <0.001, ANOVA

Population analysed: The Per-protocol Immunogenicity population included all participants who were not protocol violators, received all 3 vaccinations of mid-dose V503 or Gardasil within acceptable ranges, were seronegative at Day 1 and PCR negative from Day 1- Month 7 for the relevant HPV types, and had a Month 7 serum sample collected within an acceptable range

Primary outcome: Base Study: Percentage of Participants With One or More Adverse Event

Time frame: Up to Month 7 (low- and high-dose V503) or up to Month 54 (mid-dose V503 and Gardasil). Number. Unit: Percentage of participants

Measure	Low-dose V503 n = 310	Mid-dose V503 n = 7071	High-dose V503 n = 305	Gardasil n = 7078
Value	92.6	94.2	92.8	91.1

Population analysed: The analysis population included all participants who received \>=1 vaccination and had safety follow-up

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Base Study: SAEs up to Month (M) 7 (low- and high-dose V503) or up to M54 (mid-dose V503 and Gardasil); non-serious AEs up to Day 15 after vaccination. Cohort 1: SAEs M60 to 61; non-serious AEs up to Day 15 after vaccination 4. Cohort 2: SAEs M60 to 67.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Base Study: Low-Dose V503	4 of 310 (1.3%)	278 of 310 (89.7%)	Not reported
Base Study: Mid-dose V503	233 of 7,071 (3.3%)	6,551 of 7,071 (92.6%)	Not reported
Base Study: High-dose V503	5 of 305 (1.6%)	280 of 305 (91.8%)	Not reported
Base Study: Gardasil	184 of 7,078 (2.6%)	6,268 of 7,078 (88.6%)	Not reported
Extension Study: Mid-dose V503 (Cohort 1)	1 of 150 (0.7%)	130 of 150 (86.7%)	Not reported
Extension Study: Mid-dose V503 (Cohort 2)	25 of 3,049 (0.8%)	89 of 3,049 (2.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 25912208Luxembourg A, Brown D, Bouchard C, Giuliano AR, Iversen OE, Joura EA, Penny ME, Restrepo JA, Romaguera J, Maansson R, Moeller E, Ritter M, Chen J. Phase II studies to select the formulation of a multivalent HPV L1 virus-like particle (VLP) vaccine. Hum Vaccin Immunother. 2015;11(6):1313-22. doi: 10.1080/21645515.2015.1012010.
Results publication: PubMed 25693011Joura EA, Giuliano AR, Iversen OE, Bouchard C, Mao C, Mehlsen J, Moreira ED Jr, Ngan Y, Petersen LK, Lazcano-Ponce E, Pitisuttithum P, Restrepo JA, Stuart G, Woelber L, Yang YC, Cuzick J, Garland SM, Huh W, Kjaer SK, Bautista OM, Chan IS, Chen J, Gesser R, Moeller E, Ritter M, Vuocolo S, Luxembourg A; Broad Spectrum HPV Vaccine Study. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015 Feb 19;372(8):711-23. doi: 10.1056/NEJMoa1405044.
Results publication: PubMed 25278227Chen YH, Gesser R, Luxembourg A. A seamless phase IIB/III adaptive outcome trial: design rationale and implementation challenges. Clin Trials. 2015 Feb;12(1):84-90. doi: 10.1177/1740774514552110. Epub 2014 Oct 1.
Results publication: PubMed 25749310Luxembourg A, Bautista O, Moeller E, Ritter M, Chen J. Design of a large outcome trial for a multivalent human papillomavirus L1 virus-like particle vaccine. Contemp Clin Trials. 2015 May;42:18-25. doi: 10.1016/j.cct.2015.02.009. Epub 2015 Mar 3.
Results publication: PubMed 26366475Pitisuttithum P, Velicer C, Luxembourg A. 9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV. Expert Rev Vaccines. 2015;14(11):1405-19. doi: 10.1586/14760584.2015.1089174. Epub 2015 Sep 14.
Results publication: PubMed 27422279Moreira ED Jr, Block SL, Ferris D, Giuliano AR, Iversen OE, Joura EA, Kosalaraksa P, Schilling A, Van Damme P, Bornstein J, Bosch FX, Pils S, Cuzick J, Garland SM, Huh W, Kjaer SK, Qi H, Hyatt D, Martin J, Moeller E, Ritter M, Baudin M, Luxembourg A. Safety Profile of the 9-Valent HPV Vaccine: A Combined Analysis of 7 Phase III Clinical Trials. Pediatrics. 2016 Aug;138(2):e20154387. doi: 10.1542/peds.2015-4387. Epub 2016 Jul 15.
Results publication: PubMed 28886907Huh WK, Joura EA, Giuliano AR, Iversen OE, de Andrade RP, Ault KA, Bartholomew D, Cestero RM, Fedrizzi EN, Hirschberg AL, Mayrand MH, Ruiz-Sternberg AM, Stapleton JT, Wiley DJ, Ferenczy A, Kurman R, Ronnett BM, Stoler MH, Cuzick J, Garland SM, Kjaer SK, Bautista OM, Haupt R, Moeller E, Ritter M, Roberts CC, Shields C, Luxembourg A. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial. Lancet. 2017 Nov 11;390(10108):2143-2159. doi: 10.1016/S0140-6736(17)31821-4. Epub 2017 Sep 5.
Derived from this study: PubMed 41166720Joura E, Kjaer SK, Bautista O, Luxembourg A, Saah A, Giuliano A. Effect of Prior 9-Valent Human Papillomavirus Vaccination on Subsequent Lower Genital Tract Dysplasia After Cervical Excisional Surgery. Obstet Gynecol. 2026 Jan 1;147(1):73-82. doi: 10.1097/AOG.0000000000006113. Epub 2025 Oct 30.
Derived from this study: PubMed 33326342Kjaer SK, Nygard M, Sundstrom K, Munk C, Berger S, Dzabic M, Fridrich KE, Waldstrom M, Sorbye SW, Bautista O, Group T, Luxembourg A. Long-term effectiveness of the nine-valent human papillomavirus vaccine in Scandinavian women: interim analysis after 8 years of follow-up. Hum Vaccin Immunother. 2021 Apr 3;17(4):943-949. doi: 10.1080/21645515.2020.1839292. Epub 2020 Dec 16.
Derived from this study: PubMed 30982556Giuliano AR, Joura EA, Garland SM, Huh WK, Iversen OE, Kjaer SK, Ferenczy A, Kurman RJ, Ronnett BM, Stoler MH, Bautista OM, Moeller E, Ritter M, Shields C, Luxembourg A. Nine-valent HPV vaccine efficacy against related diseases and definitive therapy: comparison with historic placebo population. Gynecol Oncol. 2019 Jul;154(1):110-117. doi: 10.1016/j.ygyno.2019.03.253. Epub 2019 Apr 11.
Derived from this study: PubMed 29767739Garland SM, Pitisuttithum P, Ngan HYS, Cho CH, Lee CY, Chen CA, Yang YC, Chu TY, Twu NF, Samakoses R, Takeuchi Y, Cheung TH, Kim SC, Huang LM, Kim BG, Kim YT, Kim KH, Song YS, Lalwani S, Kang JH, Sakamoto M, Ryu HS, Bhatla N, Yoshikawa H, Ellison MC, Han SR, Moeller E, Murata S, Ritter M, Sawata M, Shields C, Walia A, Perez G, Luxembourg A. Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries. J Infect Dis. 2018 Jun 5;218(1):95-108. doi: 10.1093/infdis/jiy133.
Derived from this study: PubMed 29269325Ruiz-Sternberg AM, Moreira ED Jr, Restrepo JA, Lazcano-Ponce E, Cabello R, Silva A, Andrade R, Revollo F, Uscanga S, Victoria A, Guevara AM, Luna J, Plata M, Dominguez CN, Fedrizzi E, Suarez E, Reina JC, Ellison MC, Moeller E, Ritter M, Shields C, Cashat M, Perez G, Luxembourg A. Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women. Papillomavirus Res. 2018 Jun;5:63-74. doi: 10.1016/j.pvr.2017.12.004. Epub 2017 Dec 19.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Comparator: GARDASIL and Experimental: V503 in people with Cervical Cancer and Vulvar Cancer, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Disease (Test of Hypothesis) (time frame: From Day 1 until >=30 cases accumulate, up to Month 54 in the base study). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00543543, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2018.