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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00543543
First received: October 12, 2007
Last updated: June 25, 2015
Last verified: June 2015
  Purpose

The purpose of this study is to evaluate the safety, efficacy, and immunogenicity of V503 in comparison to GARDASIL. The primary hypotheses tested in the study are 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.


Condition Intervention Phase
Cervical Cancer
Vulvar Cancer
Vaginal Cancer
Genital Warts
Human Papillomavirus Infection
Biological: Comparator: GARDASIL
Biological: Experimental: V503
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.

  • Extension Study: Geometric Mean Titers to HPV Types 6/11/16/18/31/33/45/52/58 [ Time Frame: Day 7 and Day 28 postdose 4 in the extension study ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 14840
Study Start Date: September 2007
Estimated Study Completion Date: October 2015
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Base Study Part A: GARDASIL
GARDASIL 0.5 mL injection in 3-dose regimen in the base study Part A. Participants in this arm who receive ≥1 dose of GARDASIL in base study Part A can enter the extension study and receive a 3-dose regimen of V503 at the dose administered in Part B.
Biological: Comparator: GARDASIL
GARDASIL (quadrivalent HPV [Types 6, 11, 16, and 18] L1 virus-like particle vaccine), 0.5 mL injection in 3 dose regimen
Experimental: Base Study Part A: V503 Low Dose
V503 low dose, 0.5 mL injection in 3-dose regimen
Biological: Experimental: V503
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
Experimental: Base Study Part A: V503 Mid Dose
V503 mid dose, 0.5 mL injection in 3-dose regimen
Biological: Experimental: V503
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
Experimental: Base Study Part A: V503 High Dose
V503 high dose, 0.5 mL injection in 3-dose regimen
Biological: Experimental: V503
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
Experimental: Base Study Part B: V503
V503 (dose to be selected after Part A is complete), 0.5 mL in 3-dose regimen. Approximately 150 participants in this arm will receive a fourth dose of V503 in the extension study.
Biological: Experimental: V503
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
Active Comparator: Base Study Part B: GARDASIL
GARDASIL 0.5 mL injection in 3-dose regimen in the base study. Participants in this arm who receive ≥1 dose of GARDASIL in the base study can enter the extension study and receive a 3-dose regimen of V503 at the dose administered in Part B.
Biological: Comparator: GARDASIL
GARDASIL (quadrivalent HPV [Types 6, 11, 16, and 18] L1 virus-like particle vaccine), 0.5 mL injection in 3 dose regimen

Detailed Description:

The study includes a double-blind, dose-finding evaluation of a 3-dose regimen of 3 dose formulations of V503 and GARDASIL (Base Study Part A), a double-blind, safety/efficacy evaluation of a 3-dose regimen of the V503 dose formulation selected in Part A and GARDASIL (Base Study Part B), and an open-label extension consisting of 2 substudies: an evaluation of immune memory in participants receiving a fourth vaccination with V503 (Extension Cohort 1) and an opportunity for participants who received GARDASIL in the base study to receive a 3-dose regimen of V503 (Extension Cohort 2).

  Eligibility

Ages Eligible for Study:   16 Years to 26 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Female between 16- to 26-years-old
  • Has never had Pap testing or has only had normal Pap test results
  • For the immune memory substudy in the extension (Cohort 1): was randomized to V503 in Part B of 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 either Part A or Part B of 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.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00543543

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00543543     History of Changes
Other Study ID Numbers: V503-001, 2007_538
Study First Received: October 12, 2007
Results First Received: December 12, 2014
Last Updated: June 25, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Papillomavirus Infections
Uterine Cervical Neoplasms
Vaginal Neoplasms
Vulvar Neoplasms
DNA Virus Infections
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Tumor Virus Infections
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Vaginal Diseases
Virus Diseases
Vulvar Diseases

ClinicalTrials.gov processed this record on August 26, 2015