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

NCT00543543 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: V503-0012007_538
• Study Type: interventional
• Target: 14,840
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Cervical Cancer; Vulvar Cancer; Vaginal Cancer; Genital Warts; Human Papillomavirus Infection

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Up to Month 6

Secondary Outcomes (2)

• Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Persistent Infection

  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

  4 weeks postdose 3

Other Outcomes (3)

• Extension Study: Geometric Mean Titers to HPV Types 6/11/16/18/31/33/45/52/58 at Predose 4

  Month 60: predose 4 in the Extension Study (Cohort 1)

• Extension Study: Geometric Mean Titers to HPV Types 6/11/16/18/31/33/45/52/58 at Day 7 Postdose 4

  Month 60 + 1 week: Day 7 postdose 4 in the Extension Study (Cohort 1)

• Extension Study: Geometric Mean Titers to HPV Types 6/11/16/18/31/33/45/52/58 at Day 28 Postdose 4

  Month 61: 28 days postdose 4 in the Extension Study (Cohort 1)

Study Arms (4)

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.

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.

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.

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.

Biological: Comparator: GARDASIL; Biological: Experimental: V503

Interventions

Comparator: GARDASIL BIOLOGICAL

GARDASIL (quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine), 0.5 mL injection in 3 dose regimen

Gardasil

Experimental: V503 BIOLOGICAL

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).

Gardasil; High-dose V503; Low-dose V503; Mid-dose V503

Eligibility Criteria

• Age: 16 Years - 26 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (14)

• 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.

  PMID: 25912208 RESULT

• 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.

  PMID: 25693011 RESULT

• 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.

  PMID: 25278227 RESULT

• 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.

  PMID: 25749310 RESULT

• 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.

  PMID: 26366475 RESULT

• 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.

  PMID: 27422279 RESULT

• 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.

  PMID: 28886907 RESULT

• 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.

  PMID: 41166720 DERIVED

• 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.

  PMID: 33326342 DERIVED

• 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.

  PMID: 30982556 DERIVED

• 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.

  PMID: 29767739 DERIVED

• 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.

  PMID: 29269325 DERIVED

• 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.

  PMID: 29211620 DERIVED

• 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.

  PMID: 28789851 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Vulvar Neoplasms; Vaginal Neoplasms; Condylomata Acuminata; Papillomavirus Infections

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Vulvar Diseases; Vaginal Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Warts; Skin Diseases, Viral; Tumor Virus Infections; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2007
• First Posted: October 15, 2007
• Study Start: September 24, 2007
• Primary Completion: April 10, 2013
• Study Completion: July 7, 2016
• Last Updated: November 27, 2018
• Results First Posted: December 19, 2014

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share