Clinical trial NCT00543543: Broad Spectrum HPV (Human Papillomavirus) Vaccine Study in 16-to 26-Year-Old Women (V503-001)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cervical Cancer
Vulvar Cancer
Vaginal Cancer
Genital Warts
Human Papillomavirus Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2007-10-15
Enrollment: 14840
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 26
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

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.)

Primary outcomes:
measure: Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Disease (Test of Hypothesis)
timeFrame: From Day 1 until >=30 cases accumulate, up to Month 54 in the base study
measure: Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Disease (End-of-study Update)
timeFrame: Up to Month 54 in the base study
measure: Base Study: Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18/31/33/45/52/58
timeFrame: 4 weeks postdose 3 in the base study
measure: Base Study: Percentage of Participants With One or More Adverse Event
timeFrame: Up to Month 7 (low- and high-dose V503) or up to Month 54 (mid-dose V503 and Gardasil)
measure: Base Study: Percentage of Participants With One or More Injection-site Adverse Event
timeFrame: Up to Day 5 after any vaccination
measure: Base Study: Percentage of Participants With One or More Non-injection-site (Systemic) Adverse Event
timeFrame: Up to Day 15 after any vaccination
measure: Base Study: Percentage of Participants With One or More Vaccine-related Adverse Event
timeFrame: Up to Month 7 (low- and high-dose V503) or up to Month 54 (mid-dose V503 and Gardasil)
measure: Base Study: Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event
timeFrame: Up to Month 6
Secondary outcomes:
measure: Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Persistent Infection
timeFrame: Up to Month 54 in the base study
measure: Base Study: Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58
timeFrame: 4 weeks postdose 3
Other outcomes:
measure: Extension Study: Geometric Mean Titers to HPV Types 6/11/16/18/31/33/45/52/58 at Predose 4
timeFrame: Month 60: predose 4 in the Extension Study (Cohort 1)
measure: Extension Study: Geometric Mean Titers to HPV Types 6/11/16/18/31/33/45/52/58 at Day 7 Postdose 4
timeFrame: Month 60 + 1 week: Day 7 postdose 4 in the Extension Study (Cohort 1)
measure: Extension Study: Geometric Mean Titers to HPV Types 6/11/16/18/31/33/45/52/58 at Day 28 Postdose 4
timeFrame: Month 61: 28 days postdose 4 in the Extension Study (Cohort 1)
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
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