HPV 16 Infection
Conditions
Brief summary
Subjects received HPV 16 L1 VLP vaccine or placebo (1:1 ratio). Endpoints included efficacy, immunogenicity, and safety.
Interventions
BIOLOGICALComparator: HPV 16 L1 Vaccine
A 0.5 intramuscular injection given at Day 1, Month 2, and Month 6
BIOLOGICALComparator: Placebo
A 0.5 intramuscular placebo injection given 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, unmarried females age 16 to 23 years with intact uteri * Not pregnant at enrollment * Agreed to use effective contraception through Month 7 of the study * A lifetime history of 0 to 5 male partners with whom the subjects engaged in at least one episode of insertive intercourse
Exclusion criteria
* No prior history of Human Papillomavirus (HPV) vaccination * No receipt of any other vaccination within 1 month prior to enrollment or plans to receive any other vaccination within 1 month prior to or after any dose of study vaccine * No prior history of an abnormal Papanicolaou (Pap) test showing Squamous intraepithelial lesion (SIL) or biopsy showing Cervical intraepithelial neoplasia (CIN)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Anti-HPV 16 Geometric Mean Titers | Month 7 | The limit of detection of the assay was 6 mMU/ml. Samples with titer below the limit of detection were assigned a value of 3 for calculation of GMT and confidence interval. GMTs and confidence limits below the limit of detection are shown as 6.0. |
| Incidence of Persistent HPV 16 Infection | Through Month 48 | Cases of persistent infection were those with detection of HPV 16 by PCR (Polymerase chain reaction) on at least 2 consecutive visits at least 4 months apart; or detection of HPV 16 in a cervical biopsy specimen showing pathologic evidence of CIN1 (Cervical intraepithelial neoplasia), CIN2 or CIN3 together with HPV 16 detected at the visit immediately before or after the biopsy; or detection of HPV 16 on a subject's last visit. |
| Incidence of HPV 16-related CIN1, CIN2 or C1N3 | Through Month 48 | Cases of HPV 16-related CIN1, CIN2 or CIN3 are those with detection of HPV 16 in a cervical biopsy specimen showing pathologic evidence of CIN1, CIN2 or CIN3 together with HPV 16 detected at the visit immediately before or after the biopsy. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HPV 16 L1 VLP (Group 1) The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 1 were vaccinated (at Day 1, Month 2, and Month 6) with HPV (Human Papillomavirus) 16 Virus-Like Particle (VLP) Vaccine.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received the HPV 16 VLP Vaccine from completion of the Vaccination Period at Month 7 through Month 48. | 1,204 |
| Placebo (Group 2) The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 2 were vaccinated (at Day 1, Month 2, and Month 6) with placebo.
The Follow-up Period for the Base Study encompassed the follow-up of subjects who had received placebo from completion of the Vaccination Period at Month 7 through Month 48. | 1,205 |
| Total | 2,409 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Extension | Adverse Event | 0 | 0 | 1 |
| Extension | Lost to Follow-up | 0 | 0 | 57 |
| Extension | Moved | 0 | 0 | 8 |
| Extension | Other | 0 | 0 | 31 |
| Extension | Protocol Violation | 0 | 0 | 2 |
| Extension | Withdrawal by Subject | 0 | 0 | 98 |
| Follow-up (Month 7 Though Month 48) | Lost to Follow-up | 67 | 69 | 0 |
| Follow-up (Month 7 Though Month 48) | Moved | 6 | 5 | 0 |
| Follow-up (Month 7 Though Month 48) | Other | 11 | 21 | 0 |
| Follow-up (Month 7 Though Month 48) | Pregnancy | 0 | 1 | 0 |
| Follow-up (Month 7 Though Month 48) | Protocol Violation | 1 | 2 | 0 |
| Follow-up (Month 7 Though Month 48) | Withdrawal by Subject | 73 | 104 | 0 |
| Vaccination (Day 1 to Month 7) | Adverse Event | 4 | 5 | 0 |
| Vaccination (Day 1 to Month 7) | Lost to Follow-up | 88 | 75 | 0 |
| Vaccination (Day 1 to Month 7) | Other | 17 | 9 | 0 |
| Vaccination (Day 1 to Month 7) | Pregnancy | 19 | 14 | 0 |
| Vaccination (Day 1 to Month 7) | Protocol Violation | 22 | 13 | 0 |
| Vaccination (Day 1 to Month 7) | Randomized Not Vaccinated | 11 | 7 | 0 |
| Vaccination (Day 1 to Month 7) | Withdrawal by Subject | 50 | 44 | 0 |
Baseline characteristics
| Characteristic | Placebo (Group 2) | Total | HPV 16 L1 VLP (Group 1) |
|---|---|---|---|
| Age, Continuous | 20.1 years | 20.1 years | 20.0 years |
| Race/Ethnicity, Customized Asian | 73 participants | 142 participants | 69 participants |
| Race/Ethnicity, Customized Black | 114 participants | 208 participants | 94 participants |
| Race/Ethnicity, Customized Hispanic American | 93 participants | 182 participants | 89 participants |
| Race/Ethnicity, Customized Native American | 14 participants | 23 participants | 9 participants |
| Race/Ethnicity, Customized Other | 22 participants | 47 participants | 25 participants |
| Race/Ethnicity, Customized White | 889 participants | 1807 participants | 918 participants |
| Sex: Female, Male Female | 1205 Participants | 2409 Participants | 1204 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1,025 / 1,191 | 1,013 / 1,196 | 0 / 0 |
| serious Total, serious adverse events | 19 / 1,191 | 20 / 1,196 | 1 / 400 |
Outcome results
Primary
Incidence of HPV 16-related CIN1, CIN2 or C1N3
Cases of HPV 16-related CIN1, CIN2 or CIN3 are those with detection of HPV 16 in a cervical biopsy specimen showing pathologic evidence of CIN1, CIN2 or CIN3 together with HPV 16 detected at the visit immediately before or after the biopsy.
Time frame: Through Month 48
Population: Per-protocol population: subjects must have no major protocol violations, must be seronegative to HPV 16 at Day 1 and PCR negative to HPV 16 through Month 7, and must provide follow-up data after Month 7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HPV 16 L1 VLP (Group 1) | Incidence of HPV 16-related CIN1, CIN2 or C1N3 | 0.0 Incidence per 100 person-years |
| Placebo (Group 2) | Incidence of HPV 16-related CIN1, CIN2 or C1N3 | 1.0 Incidence per 100 person-years |
95% CI: [84, 100]
Primary
Incidence of Persistent HPV 16 Infection
Cases of persistent infection were those with detection of HPV 16 by PCR (Polymerase chain reaction) on at least 2 consecutive visits at least 4 months apart; or detection of HPV 16 in a cervical biopsy specimen showing pathologic evidence of CIN1 (Cervical intraepithelial neoplasia), CIN2 or CIN3 together with HPV 16 detected at the visit immediately before or after the biopsy; or detection of HPV 16 on a subject's last visit.
Time frame: Through Month 48
Population: Per-protocol population: subjects must have no major protocol violations, must be seronegative to HPV 16 at Day 1 and PCR (Polymerase chain reaction) negative to HPV 16 through Month 7, and must provide follow-up data after Month 7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HPV 16 L1 VLP (Group 1) | Incidence of Persistent HPV 16 Infection | 0.3 Incidence per 100 person-years |
| Placebo (Group 2) | Incidence of Persistent HPV 16 Infection | 4.9 Incidence per 100 person-years |
95% CI: [87.8, 97.7]
Primary
Serum Anti-HPV 16 Geometric Mean Titers
The limit of detection of the assay was 6 mMU/ml. Samples with titer below the limit of detection were assigned a value of 3 for calculation of GMT and confidence interval. GMTs and confidence limits below the limit of detection are shown as 6.0.
Time frame: Month 7
Population: Per-protocol population: subjects must have no major protocol violations, must be seronegative to HPV 16 at Day 1 and PCR negative to HPV 16 through Month 7, and must provide serology data at Month 7
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| HPV 16 L1 VLP (Group 1) | Serum Anti-HPV 16 Geometric Mean Titers | 1518.8 milliMerck units/ml (mMU/ml) |
| Placebo (Group 2) | Serum Anti-HPV 16 Geometric Mean Titers | 6.0 milliMerck units/ml (mMU/ml) |