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NCT00543543 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2018-11-27

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Base Study: Percentage of Participants With One or More Injection-site Adverse Event

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outcome · POSTED

Base Study: Percentage of Participants With One or More Non-injection-site (Systemic) Adverse Event

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outcome · POSTED

Base Study: Percentage of Participants With One or More Vaccine-related Adverse Event

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outcome · POSTED

Base Study: Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event

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outcome · POSTED

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

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outcome · POSTED

Base Study: Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58

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outcome · POSTED

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

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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.)
healthy Volunteers
true
maximum Age
26 Years
minimum Age
16 Years
sex
FEMALE
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    V503 (9-Valent Human Papillomavirus \[HPV\] Vaccine) low-dose 0.5 mL injection in a 3-dose regimen in the base study.
    intervention Names
    1. Biological: Experimental: V503
    label
    Low-dose V503
    type
    EXPERIMENTAL
  2. description
    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.
    intervention Names
    1. Biological: Experimental: V503
    label
    Mid-dose V503
    type
    EXPERIMENTAL
  3. description
    V503 (9-Valent HPV Vaccine) high-dose 0.5 mL injection in a 3-dose regimen in the base study.
    intervention Names
    1. Biological: Experimental: V503
    label
    High-dose V503
    type
    EXPERIMENTAL
  4. description
    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.
    intervention Names
    1. Biological: Comparator: GARDASIL
    2. Biological: Experimental: V503
    label
    Gardasil
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Gardasil
    description
    GARDASIL (quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine), 0.5 mL injection in 3 dose regimen
    name
    Comparator: GARDASIL
    type
    BIOLOGICAL
  2. arm Group Labels
    1. Gardasil
    2. High-dose V503
    3. Low-dose V503
    4. Mid-dose V503
    description
    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).
    name
    Experimental: V503
    type
    BIOLOGICAL
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
DOUBLE
who Masked
  1. PARTICIPANT
  2. INVESTIGATOR
primary Purpose
PREVENTION
Enrollment
count
14840
type
ACTUAL
Registered outcome plans (not posted results)
other Outcomes
  1. description
    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. This outcome measure applied to Cohort 1 participants only.
    measure
    Extension Study: Geometric Mean Titers to HPV Types 6/11/16/18/31/33/45/52/58 at Predose 4
    time Frame
    Month 60: predose 4 in the Extension Study (Cohort 1)
  2. description
    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. This outcome measure applied to Cohort 1 participants only.
    measure
    Extension Study: Geometric Mean Titers to HPV Types 6/11/16/18/31/33/45/52/58 at Day 7 Postdose 4
    time Frame
    Month 60 + 1 week: Day 7 postdose 4 in the Extension Study (Cohort 1)
  3. description
    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. This outcome measure applied to Cohort 1 participants only.
    measure
    Extension Study: Geometric Mean Titers to HPV Types 6/11/16/18/31/33/45/52/58 at Day 28 Postdose 4
    time Frame
    Month 61: 28 days postdose 4 in the Extension Study (Cohort 1)
primary Outcomes
  1. description
    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.
    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
  2. description
    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.
    measure
    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
  3. description
    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.
    measure
    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
  4. description
    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.
    measure
    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)
  5. description
    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.
    measure
    Base Study: Percentage of Participants With One or More Injection-site Adverse Event
    time Frame
    Up to Day 5 after any vaccination
  6. description
    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.
    measure
    Base Study: Percentage of Participants With One or More Non-injection-site (Systemic) Adverse Event
    time Frame
    Up to Day 15 after any vaccination
  7. description
    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.
    measure
    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)
  8. description
    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.
    measure
    Base Study: Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event
    time Frame
    Up to Month 6
secondary Outcomes
  1. description
    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.
    measure
    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
  2. description
    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.
    measure
    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
Full study description
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.
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).
Source references
avail Ipds
references
  1. citation
    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
    type
    RESULT
  2. citation
    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
    type
    RESULT
  3. citation
    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
    type
    RESULT
  4. citation
    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
    type
    RESULT
  5. citation
    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
    type
    RESULT
  6. citation
    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
    type
    RESULT
  7. citation
    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
    type
    RESULT
  8. citation
    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
    type
    DERIVED
  9. citation
    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
    type
    DERIVED
  10. citation
    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
    type
    DERIVED
  11. citation
    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
    type
    DERIVED
  12. citation
    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
    type
    DERIVED
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    Preserved source evidence · Not medical advice