Genital Diseases, Female, Papillomavirus Infections
Conditions
Keywords
HPV 6/11/16/18 infection and related genital disease
Brief summary
This study was conducted in 2 parts. Part A was a randomized, double-blind, placebo-controlled, multicenter, sequential dose-escalating evaluation. Part B was a randomized, double-blind (operating under in-house blinding procedures), placebo-controlled, multicenter, dose-ranging study.
Interventions
BIOLOGICALQuadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20
20/40/40/20 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
BIOLOGICALQuadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40
40/40/40/40 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
BIOLOGICALQuadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80
80/80/40/80 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
BIOLOGICALPlacebo (mcg) (Aluminum Adjuvant)225
placebo containing 225 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
BIOLOGICALPlacebo (mcg) (Aluminum Adjuvant) 450
placebo containing 450 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 23 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy females 16 to 23 years of age * Not pregnant at enrollment and must have agreed to use effective contraception through Month 7 of the study * Lifetime history of 0 to 4 male sexual partners (individuals with whom penetrative sexual intercourse occurred)
Exclusion criteria
* No prior receipt of an Human Papillomavirus (HPV) vaccine * No receipt of inactivated or recombinant vaccines within 14 days prior to enrollment or receipt of live vaccines within 21 days prior to enrollment * No prior abnormal Pap test showing squamous intraepithelial lesion (SIL) or biopsy showing cervical intraepithelial neoplasia (CIN) * No prior history of genital warts or treatment for genital warts
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Subjects With Injection Site Adverse Experiences | Days 1-5 following any vaccination visit |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of HPV 6-, 11-, 16- or 18-related Persistent Infection or Disease (Cervical Intraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia, Vaginal Intraepithelial Neoplasia, Adenocarcinoma in Situ, Cervical Cancer, and Genital Warts) | Through 36 Months |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20 The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 1 received a 20/40/40/20 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36. | 290 |
| Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40 The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 2 received a 40/40/40/40 formulation of quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36. | 284 |
| Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80 The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 3 received a 80/80/40/80 formulation of quadrivalent human papillomavirus (qHPV) (Types 6, 11, 16, 18) L1 Virus-Like Particle (VLP) vaccine at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36. | 292 |
| Placebo (mcg) (Aluminum Adjuvant) 225 The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 4 received placebo containing 225 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36. | 146 |
| Placebo (mcg) (Aluminum Adjuvant) 450 The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time subjects in Group 5 received placebo containing 450 mcg of aluminum adjuvant per dose at Day 1, Month 2, and Month 6.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the qHPV 16 VLP Vaccine or placebo from completion of the Vaccination Period at Month 7 through Month 36. | 146 |
| Total | 1,158 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Base Study (Day 1 to Month 7) | Adverse Event | 0 | 2 | 0 | 0 | 1 | 0 | 0 |
| Base Study (Day 1 to Month 7) | Lost to Follow-up | 4 | 6 | 6 | 4 | 0 | 0 | 0 |
| Base Study (Day 1 to Month 7) | Other | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Base Study (Day 1 to Month 7) | Pregnancy | 3 | 2 | 3 | 1 | 1 | 0 | 0 |
| Base Study (Day 1 to Month 7) | Protocol Violation | 1 | 2 | 0 | 1 | 2 | 0 | 0 |
| Base Study (Day 1 to Month 7) | Randomized Not Vaccinated | 1 | 2 | 0 | 0 | 0 | 0 | 0 |
| Base Study (Day 1 to Month 7) | Withdrawal by Subject | 12 | 9 | 12 | 4 | 3 | 0 | 0 |
| Extension 1 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Extension 1 | Moved | 0 | 0 | 0 | 0 | 0 | 4 | 0 |
| Extension 1 | Other | 0 | 0 | 0 | 0 | 0 | 9 | 0 |
| Extension 1 | Pregnancy | 0 | 0 | 0 | 0 | 0 | 4 | 0 |
| Extension 1 | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Extension 1 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 3 | 0 |
| Extension 2 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Extension 2 | Other | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Extension 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 5 |
| Long Term Follow-up (Month 7 toMonth 36) | Lost to Follow-up | 6 | 8 | 5 | 4 | 3 | 0 | 0 |
| Long Term Follow-up (Month 7 toMonth 36) | Moved | 3 | 2 | 1 | 2 | 0 | 0 | 0 |
| Long Term Follow-up (Month 7 toMonth 36) | Other | 2 | 0 | 0 | 0 | 1 | 0 | 0 |
| Long Term Follow-up (Month 7 toMonth 36) | Proceeded to Extension 1 | 114 | 0 | 0 | 69 | 75 | 0 | 0 |
| Long Term Follow-up (Month 7 toMonth 36) | Protocol Violation | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Long Term Follow-up (Month 7 toMonth 36) | Withdrawal by Subject | 7 | 4 | 13 | 4 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20 | Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40 | Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80 | Placebo (mcg) (Aluminum Adjuvant) 225 | Placebo (mcg) (Aluminum Adjuvant) 450 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 20.2 years | 20.0 years | 20.1 years | 20.0 years | 20.1 years | 20.0 years |
| Race/Ethnicity, Customized Asian | 7 participants | 11 participants | 5 participants | 6 participants | 5 participants | 34 participants |
| Race/Ethnicity, Customized Black | 25 participants | 32 participants | 27 participants | 12 participants | 7 participants | 103 participants |
| Race/Ethnicity, Customized Hispanic American | 15 participants | 15 participants | 10 participants | 10 participants | 11 participants | 61 participants |
| Race/Ethnicity, Customized Indian | 0 participants | 0 participants | 2 participants | 0 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Multi-racial | 13 participants | 9 participants | 6 participants | 7 participants | 4 participants | 39 participants |
| Race/Ethnicity, Customized Native American | 2 participants | 4 participants | 2 participants | 0 participants | 1 participants | 9 participants |
| Race/Ethnicity, Customized White | 228 participants | 213 participants | 240 participants | 111 participants | 118 participants | 910 participants |
| Sex: Female, Male Female | 290 Participants | 284 Participants | 292 Participants | 146 Participants | 146 Participants | 1158 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 245 / 288 | 247 / 282 | 263 / 292 | 105 / 146 | 114 / 146 | 180 / 241 |
| serious Total, serious adverse events | 3 / 288 | 0 / 282 | 2 / 292 | 0 / 146 | 3 / 146 | 1 / 241 |
Outcome results
Primary
Number of Subjects With Injection Site Adverse Experiences
Time frame: Days 1-5 following any vaccination visit
Population: All vaccinated subjects with adverse experience follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20 | Number of Subjects With Injection Site Adverse Experiences | 247 Participants |
| Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40 | Number of Subjects With Injection Site Adverse Experiences | 248 Participants |
| Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 80/80/40/80 | Number of Subjects With Injection Site Adverse Experiences | 266 Participants |
| Placebo (mcg) (Aluminum Adjuvant) 225 | Number of Subjects With Injection Site Adverse Experiences | 107 Participants |
| Placebo (mcg) (Aluminum Adjuvant) 450 | Number of Subjects With Injection Site Adverse Experiences | 115 Participants |
Secondary
Incidence of HPV 6-, 11-, 16- or 18-related Persistent Infection or Disease (Cervical Intraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia, Vaginal Intraepithelial Neoplasia, Adenocarcinoma in Situ, Cervical Cancer, and Genital Warts)
Time frame: Through 36 Months
Population: Per-protocol population: subjects must have no major protocol violations, must be seronegative at Day 1 and PCR negative through Month 7 to the relevant HPV type, and must provide follow-up data after Month 7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 20/40/40/20 | Incidence of HPV 6-, 11-, 16- or 18-related Persistent Infection or Disease (Cervical Intraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia, Vaginal Intraepithelial Neoplasia, Adenocarcinoma in Situ, Cervical Cancer, and Genital Warts) | 0.7 Incidence per 100 person-years |
| Quadrivalent HPV (Types 6,11,16,18) L1 VLP Vaccine 40/40/40/40 | Incidence of HPV 6-, 11-, 16- or 18-related Persistent Infection or Disease (Cervical Intraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia, Vaginal Intraepithelial Neoplasia, Adenocarcinoma in Situ, Cervical Cancer, and Genital Warts) | 6.7 Incidence per 100 person-years |
95% CI: [70.7, 97.3]