Human Papillomavirus Infection
Conditions
Keywords
Human Papillomavirus Vaccine
Brief summary
This is a randomized, open label trial of HPV (human papilloma virus) vaccine, comparing an on-time administration of the third dose with delayed administration of the third dose. All participants would receive the first and second doses according to schedule. They would be randomized to either vaccine at 6 months or vaccine at 12 months. Blood will be drawn for titers twice from all participants: pre-dose 1 and one month post third dose. We hypothesize that the GMTs in the test group (T) are non-inferior to the usual timing control group (C): H0: δ ≤ -δ0 versus H1: δ \> -δ0 where δ = log (GMTT )- log (GMTC) and δ0 is the pre-specified non-inferiority margin.
Detailed description
The recommendations for HPV vaccine include catch-up of women 18 to 26 years old. Given that a large percentage of women in this age group are attending college, a good place to access them would be through the student health services on college campuses. However, the HPV vaccine schedule of 0, 2, and 6 months is likely to be difficult to implement in a college calendar year and the immunogenicity of alternative schedules is unknown. If the immunogenicity of an altered schedule is good, then higher vaccination rates may be achievable. Aims: 1. Determine if delay in the third dose is immunologically non-inferior to the standard administration schedule (1 month post-dose 3). 2. Determine the side effect profile of a delayed third dose, in comparison to the standard schedule
Interventions
BIOLOGICALQuadrivalent human papillomavirus vaccine on-time administration
The vaccine is given in three doses: Dose 1; dose 2 given 60 days later; dose 3 given six months after dose 1.
BIOLOGICALQuadrivalent human papillomavirus vaccine delayed administration
The vaccine is given in three doses: Dose 1; dose 2 given 60 days later; dose 3 given 12 months after dose 1.
Sponsors
Merck Sharp & Dohme LLC
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 23 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-23 year old college females who are planning to return to the university for the next fall semester.
Exclusion criteria
* Pregnancy or planned pregnancy. * Prior receipt of HPV vaccine. * Greater than four lifetime sexual partners. * Immunosuppression. * Anti-coagulant therapy. * Breastfeeding. * History of abnormal pap smear. * Allergy to vaccine components.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Antibody Titers Following the Third Dose of Human Papilloma Virus (HPV) Vaccine by Virus Type and by Administration Schedule | 1 month post-dose 3 (i.e., 7 months for standard schedule and 13 months for alternative schedule) | Geomtric mean antibody titers were assessed 1 month following the third dose of human papilloma virus vaccine. Persons with baseline antibody titers that were positive to a particular type were deleted from the analysis for that particular type so that the outcome is excludes those with baseline positives (thus, sample size varies by type). Responses were compared between the two groups after dose 3 by type. |
Countries
United States
Participant flow
Recruitment details
Two hundred young women from the university community who met the eligibility criteria were recruited at the Student Health Service.
Participants by arm
| Arm | Count |
|---|---|
| 6 Month Standard Schedule Receipt of three doses of quadrivalent human papillomavirus vaccine according to the regular schedule of 0,2, and 6 months. | 100 |
| 12 Month Alternative Group 12 month Alternative Schedule Group with 3 doses of quadrivalent vaccine at 0, 2, and 12 months | 100 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 11 |
| Overall Study | Pregnancy | 0 | 1 |
Baseline characteristics
| Characteristic | 6 Month Standard Schedule | 12 Month Alternative Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 100 Participants | 100 Participants | 200 Participants |
| Age Continuous | 20.3 years STANDARD_DEVIATION 1.3 | 20.1 years STANDARD_DEVIATION 1.4 | 20.2 years STANDARD_DEVIATION 1.3 |
| Body Mass Index | 24.2 kg/m^2 STANDARD_DEVIATION 4.7 | 24.5 kg/m^2 STANDARD_DEVIATION 5.1 | 24.3 kg/m^2 STANDARD_DEVIATION 4.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 8 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) White | 83 Participants | 89 Participants | 172 Participants |
| Region of Enrollment United States | 100 participants | 100 participants | 200 participants |
| Sex: Female, Male Female | 100 Participants | 100 Participants | 200 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 57 / 100 | 55 / 100 |
| serious Total, serious adverse events | 0 / 100 | 0 / 100 |
Outcome results
Primary
Geometric Mean Antibody Titers Following the Third Dose of Human Papilloma Virus (HPV) Vaccine by Virus Type and by Administration Schedule
Geomtric mean antibody titers were assessed 1 month following the third dose of human papilloma virus vaccine. Persons with baseline antibody titers that were positive to a particular type were deleted from the analysis for that particular type so that the outcome is excludes those with baseline positives (thus, sample size varies by type). Responses were compared between the two groups after dose 3 by type.
Time frame: 1 month post-dose 3 (i.e., 7 months for standard schedule and 13 months for alternative schedule)
Population: The analysis was by intention to treat. Participants who had positive baseline antibody titers were excluded from further analyses only for the type(s) for which they were seropositive.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 6 Month Standard Schedule | Geometric Mean Antibody Titers Following the Third Dose of Human Papilloma Virus (HPV) Vaccine by Virus Type and by Administration Schedule | Type 16 | 5534 milliMerck units per mL |
| 6 Month Standard Schedule | Geometric Mean Antibody Titers Following the Third Dose of Human Papilloma Virus (HPV) Vaccine by Virus Type and by Administration Schedule | Type 11 | 1773 milliMerck units per mL |
| 6 Month Standard Schedule | Geometric Mean Antibody Titers Following the Third Dose of Human Papilloma Virus (HPV) Vaccine by Virus Type and by Administration Schedule | Type 18 | 1225 milliMerck units per mL |
| 6 Month Standard Schedule | Geometric Mean Antibody Titers Following the Third Dose of Human Papilloma Virus (HPV) Vaccine by Virus Type and by Administration Schedule | Type 6 | 1894 milliMerck units per mL |
| 12 Month Alternative Group | Geometric Mean Antibody Titers Following the Third Dose of Human Papilloma Virus (HPV) Vaccine by Virus Type and by Administration Schedule | Type 18 | 2052 milliMerck units per mL |
| 12 Month Alternative Group | Geometric Mean Antibody Titers Following the Third Dose of Human Papilloma Virus (HPV) Vaccine by Virus Type and by Administration Schedule | Type 11 | 5623 milliMerck units per mL |
| 12 Month Alternative Group | Geometric Mean Antibody Titers Following the Third Dose of Human Papilloma Virus (HPV) Vaccine by Virus Type and by Administration Schedule | Type 16 | 11832 milliMerck units per mL |
| 12 Month Alternative Group | Geometric Mean Antibody Titers Following the Third Dose of Human Papilloma Virus (HPV) Vaccine by Virus Type and by Administration Schedule | Type 6 | 4221 milliMerck units per mL |
Comparison: Non-inferiority tested against 1-sided null hypothesis (alpha=.025) that the post Dose 3 GMT ratio of the Alternate to Standard schedule was ≤ 0.5 for each HPV typep-value: 0.025ANOVA