Dose Schedule Study
Conditions
Keywords
Gardasil, Human Papillomavirus, HPV vaccine, Cervical cancer
Brief summary
To demonstrate that Gardasil® vaccine, when given to girls 11-13 years of age according to 1 of 3 alternative 3-dose schedules (0, 3, 9 months; 0, 6, 12 months; or 0, 12, 24 months), results in anti-HPV type 16 and anti-HPV type 18 responses 28 days post-dose 3 that are similar to those obtained when the vaccine is given on the standard 3-dose schedule of 0, 2, 6 months.
Detailed description
OBJECTIVES: Primary objective: To test the hypothesis that Gardasil® vaccine, when administered to girls 11-13 years of age according to 1 of 3 alternative 3-dose schedules (0,3,9 months; 0,6,12 months; or 0,12,24 months), results in anti-HPV 16 and anti-HPV 18 responses 28 days post-dose 3 that are similar to those obtained when the vaccine is administered on the standard 3-dose schedule of 0,2,6 months. Secondary objectives: 1. To test the hypothesis that Gardasil® vaccine, when administered to girls 11-13 years of age according to 1 of 3 alternative 3-dose schedules (0,3,9 months; 0,6,12 months; or 0,12,24 months), results in anti-HPV 6 and anti-HPV 11 responses 28 days post-dose 3 that are similar to those obtained when the vaccine is administered on the standard 3-dose schedule of 0,2,6 months. 2. To describe the safety profile of the administration of Gardasil® according to each of the four schedules by assessing: (i) immediate reactogenicity (reactions within 30 minutes after each injection); (ii) solicited (local reactogenicity and fever) and unsolicited events occurring during the first 7 days following each vaccination; (iii) serious adverse events occurring up to one month following the last dose of vaccine; (iv) deaths or adverse events occurring at any time determined to be vaccination-related.
Interventions
BIOLOGICALBiological: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine
Three doses of quadrivalent HPV recombinant vaccine administered at different dosing intervals in each of four study arms.
Sponsors
National Institute of Hygiene and Epidemiology, Vietnam
PATH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
11 Years to 13 Years
Healthy volunteers
Yes
Inclusion criteria
1. 11-13 years of age. 2. Signed informed consent form (both parent's & daughter's signature). 3. Good health status. 4. Able to comply with trial protocol. 5. Plans to stay at current school for duration of study.
Exclusion criteria
1. Prior HPV vaccination 2. Pregnant or lactating or intends to become pregnant during study period. 3. Apparent moderate or severe acute illness. 4. Clinical history of bleeding disorder such as hemophilia, thrombocytopenia, or anticoagulant therapy. 5. Clinical history of impaired immune responsiveness, whether due to use of immunosuppressive therapy, a genetic defect, HIV infection, or other causes. 6. Hypersensitivity to the active substances or to any of the excipients of the HPV vaccine, or such reactions to other vaccines received in the past. 7. Investigational drug or investigational vaccine administered during the period from 30 days before to 30 days after any dose of HPV vaccine.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Comparison of Antibody Response to HPV Type 16 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 25 months |
| Comparison of Antibody Response to HPV Type 18 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 25 months |
Secondary
| Measure | Time frame |
|---|---|
| Comparison of Antibody Response to HPV Type 6 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 25 months |
| Comparison of Antibody Response to HPV Type 11 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 25 months |
Countries
Vietnam
Participant flow
Recruitment details
21 schools were (1) matched according to size, urban/rural location and ethnicity; (2) assigned to one of four groups; and (3) randomized to one of four schedules All girls 11-13 years of age in these schools were eligible to participate.
Participants by arm
| Arm | Count |
|---|---|
| 0,3,9 Month Schedule | 229 |
| 0,6,12 Month Schedule | 206 |
| 0,12,24 Month Schedule | 241 |
| Standard (0,2,6 Month) Schedule | 227 |
| Total | 903 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | subject withdrawal or lost to follow up | 34 | 13 | 29 | 22 |
Baseline characteristics
| Characteristic | 0,3,9 Month Schedule | 0,6,12 Month Schedule | 0,12,24 Month Schedule | Standard (0,2,6 Month) Schedule | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 229 Participants | 206 Participants | 241 Participants | 227 Participants | 903 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Vietnam | 229 participants | 206 participants | 241 participants | 227 participants | 903 participants |
| Sex: Female, Male Female | 229 Participants | 206 Participants | 241 Participants | 227 Participants | 903 Participants |
| Sex: Female, Male Male | 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 |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 157 / 229 | 133 / 206 | 148 / 240 | 131 / 227 |
| serious Total, serious adverse events | 0 / 229 | 0 / 206 | 0 / 241 | 0 / 227 |
Outcome results
Primary
Comparison of Antibody Response to HPV Type 16 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule.
Time frame: 25 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0,3,9 Month Schedule | Comparison of Antibody Response to HPV Type 16 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 0.93 GMT ratio |
| 0,6,12 Month Schedule | Comparison of Antibody Response to HPV Type 16 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 0.99 GMT ratio |
| 0,12,24 Month Schedule | Comparison of Antibody Response to HPV Type 16 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 0.63 GMT ratio |
| Standard (0,2,6 Month) Schedule | Comparison of Antibody Response to HPV Type 16 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 1.0 GMT ratio |
Primary
Comparison of Antibody Response to HPV Type 18 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule.
Time frame: 25 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0,3,9 Month Schedule | Comparison of Antibody Response to HPV Type 18 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 0.88 GMT ratio |
| 0,6,12 Month Schedule | Comparison of Antibody Response to HPV Type 18 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 0.92 GMT ratio |
| 0,12,24 Month Schedule | Comparison of Antibody Response to HPV Type 18 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 0.77 GMT ratio |
| Standard (0,2,6 Month) Schedule | Comparison of Antibody Response to HPV Type 18 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 1.0 GMT ratio |
Secondary
Comparison of Antibody Response to HPV Type 11 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule.
Time frame: 25 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0,3,9 Month Schedule | Comparison of Antibody Response to HPV Type 11 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 0.86 GMT ratio |
| 0,6,12 Month Schedule | Comparison of Antibody Response to HPV Type 11 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 0.86 GMT ratio |
| 0,12,24 Month Schedule | Comparison of Antibody Response to HPV Type 11 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 0.96 GMT ratio |
| Standard (0,2,6 Month) Schedule | Comparison of Antibody Response to HPV Type 11 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 1.0 GMT ratio |
Secondary
Comparison of Antibody Response to HPV Type 6 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule.
Time frame: 25 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0,3,9 Month Schedule | Comparison of Antibody Response to HPV Type 6 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 1.07 GMT ratio |
| 0,6,12 Month Schedule | Comparison of Antibody Response to HPV Type 6 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 1.14 GMT ratio |
| 0,12,24 Month Schedule | Comparison of Antibody Response to HPV Type 6 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 0.64 GMT ratio |
| Standard (0,2,6 Month) Schedule | Comparison of Antibody Response to HPV Type 6 1 Month Post-dose 3 for Each Alternative Schedule Compared to the Standard Schedule. | 1.0 GMT ratio |