Human Papillomavirus Vaccine, Quadrivalent HPV Vaccine
Conditions
Keywords
human papillomavirus vaccine L1, type 6,11,16,18, HPV Vaccines, HPV L1 vaccine, quadrivalent 6,11,16,18
Brief summary
The investigators propose a randomized, open label trial of the immunogenicity of HPV vaccine among males 18-24 years old, 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 Dose 3 at 6 months or Dose 3 at 12 months. Hypothesis: The Geometric mean titers in the 12 month 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
1\. Specific Aims and Overview: The investigators propose a randomized, open label trial of HPV vaccine among males 18-24 years old, 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 Dose 3 at 6 months or Dose 3 at 12 months. Blood would be drawn for titers at twice from all participants: pre-dose 1 and one month post Dose 3. No cytology studies or DNA studies will be conducted. 1.1 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. 3. Determine the preference and compliance of the men for the timing of the third dose. 1.2 Hypothesis for non- inferiority: 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.
Interventions
BIOLOGICALquadrivalent human papillomavirus vaccine
0.5 mL of quadrivalent HPV vaccine at enrollment, 2 months, and 12 months
Sponsors
Merck Sharp & Dohme LLC
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 26 Years
Healthy volunteers
Yes
Inclusion criteria
* Males age 18-26
Exclusion criteria
* Hospitalization within the past year * Previous HPV vaccination \>/=5 sexual partners (i.e., insertive intercourse) No other drug studies within 30 days of proposed HPV vaccination * History of genital warts * Immunosuppression * Other vaccines within 8 days of proposed HPV vaccination * Hypersensitivity to yeast or HPV vaccine components * Known autoimmune disorders * Receipt of immunoglobulins or blood product within 90 days of enrollment (may defer until 90 days completed) * Serious Adverse Reaction to HPV vaccine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity After Dose 3 | 1 month after dose 3 (e.g., month 7 if third dose at 6months or month 13 if third dose at 12 months) | Geometric mean titer (GMT) and 95% confidence intervals around titer 1 month after dose 3 in per protocol population, comparing the two groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compliance With 3rd Dose | at 3rd dose (i.e., at month 6 or month 12, depending on arm) | Determine the compliance of the men for the timing of the third dose. |
| Safety Profile | 1 week after vaccination | Total proportion of side effects reported after any dose, compared by arm. |
Countries
United States
Participant flow
Recruitment details
From October 2010 through May 2011, college age men, ages 18-25 years, were recruited using a variety of strategies including fliers, class announcements, recommendations by university health centers, emails to campus organizations, bus and campus newspaper advertisements, and targeted Facebook® advertisements.
Pre-assignment details
Exclusion criteria were: \>4 lifetime sexual partners, health problems that would interfere with the immune response or ability to complete the study, a hospitalization during the past year, hypersensitivity to yeast or HPV vaccine components, inability to complete appointments, received HPV vaccine or immunosuppressive medications.
Participants by arm
| Arm | Count |
|---|---|
| 12 Month Administration Administration of 3rd dose at 12 months
quadrivalent human papillomavirus vaccine : 0.5 mL of quadrivalent HPV vaccine at enrollment, 2 months, and 12 months | 111 |
| 6 Month Administration 3rd dose administration at 6 months
quadrivalent human papillomavirus vaccine : 0.5 mL of quadrivalent HPV vaccine at enrollment, 2 months, and 6 months | 109 |
| Total | 220 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 14 | 2 |
Baseline characteristics
| Characteristic | 6 Month Administration | 12 Month Administration | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 9 Participants | 10 Participants | 19 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 100 Participants | 101 Participants | 201 Participants |
| Age, Continuous | 21.4 years STANDARD_DEVIATION 2.2 | 21.3 years STANDARD_DEVIATION 2.3 | 21.3 years STANDARD_DEVIATION 2.2 |
| Region of Enrollment United States | 109 participants | 111 participants | 220 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 109 Participants | 111 Participants | 220 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 111 | 0 / 109 |
| serious Total, serious adverse events | 0 / 111 | 0 / 109 |
Outcome results
Primary
Immunogenicity After Dose 3
Geometric mean titer (GMT) and 95% confidence intervals around titer 1 month after dose 3 in per protocol population, comparing the two groups.
Time frame: 1 month after dose 3 (e.g., month 7 if third dose at 6months or month 13 if third dose at 12 months)
Population: Intention-to-treat
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 12 Month Administration | Immunogenicity After Dose 3 | HPV 6 | 1063 mM units/ml |
| 12 Month Administration | Immunogenicity After Dose 3 | HPV 11 | 1961 mM units/ml |
| 12 Month Administration | Immunogenicity After Dose 3 | HPV 16 | 6186 mM units/ml |
| 12 Month Administration | Immunogenicity After Dose 3 | HPV 18 | 1049 mM units/ml |
| 6 Month Administration | Immunogenicity After Dose 3 | HPV 18 | 709 mM units/ml |
| 6 Month Administration | Immunogenicity After Dose 3 | HPV 6 | 794 mM units/ml |
| 6 Month Administration | Immunogenicity After Dose 3 | HPV 16 | 4555 mM units/ml |
| 6 Month Administration | Immunogenicity After Dose 3 | HPV 11 | 1043 mM units/ml |
Comparison: The primary endpoint would demonstrate noninferiority if the upper bound of the 95% two-sided confidence interval (CI) of the ratio of GMT for Standard schedule group divided by that of Alternate schedule group is \<1.5.
Secondary
Compliance With 3rd Dose
Determine the compliance of the men for the timing of the third dose.
Time frame: at 3rd dose (i.e., at month 6 or month 12, depending on arm)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 12 Month Administration | Compliance With 3rd Dose | 97 participants |
| 6 Month Administration | Compliance With 3rd Dose | 107 participants |
Secondary
Safety Profile
Total proportion of side effects reported after any dose, compared by arm.
Time frame: 1 week after vaccination
Population: Intention-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 12 Month Administration | Safety Profile | 28.9 percentage of doses with side effects |
| 6 Month Administration | Safety Profile | 24.4 percentage of doses with side effects |
Comparison: null hypothsesis: no difference in proportion of side effects reported between groupsp-value: 0.26Chi-squared