Papillomavirus Infections
Conditions
Keywords
Papillomavirus vaccines, Uterine cervical cancer, Human Papilloma Virus infections
Brief summary
This study will evaluate the safety, tolerability, and immunogenicity of V503 in Japanese girls between the ages of 9 and 15 and will determine whether V503 induces an acceptable immune response to all human papillomavirus (HPV) strains contained in the vaccine. The success criterion for the primary analysis requires that point estimates for seroconversion rate be greater than 90% for all 9 HPV types.
Interventions
BIOLOGICALV503
V503 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
9 Years to 15 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant is in good physical health- * Participant's parent/legal guardian is able to read, understand, and complete the vaccine report card * Participant's parent/legal guardian agrees to provide a phone number for follow-up purposes * Participant is not sexually active and does not plan to become sexually active during the time from Day 1 to Month 7 of the study
Exclusion criteria
* Participant has a history of severe allergic reaction that required medical intervention * Participant has thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injection * Participant is pregnant * Participant intends to donate blood during the time from Day 1 to Month 7 of the study * Participant is immunocompromised or has been diagnosed as having a congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition. * Participant has had a splenectomy * Participant has received any of the following immunosuppressive therapies in the year prior to enrollment: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (Arava), tumor necrosis factor alpha (TNF-α) antagonists, monoclonal antibody therapies, antilymphocyte sera, or other therapy known to interfere with the immune response. * Participant has received any immune globulin product or blood-derived product in the three months prior to the Day 1 vaccination, or plans to receive any such product through Month 7 of the study * Participant has received any inactivated vaccines within 14 days of the Day 1 vaccination or any live vaccines within 28 days of the Day 1 vaccination * Participant has received a marketed HPV vaccine or has participated in an HPV vaccine clinical trial * Participant has had a fever (oral temperature ≥37.8°C) within 24 hours of the Day 1 vaccination * Participant has a history of a positive test for HPV or history of genital warts
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine | 4 weeks post-vaccination 3 (Month 7) | Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using competitive luminex immunoassay (cLIA). The serostatus cutoffs (milli Merck U/mL) for HPV types were as follows: HPV Type 6: ≥30, HPV Type 11: ≥16; HPV Type 16: ≥20, HPV Type 18: ≥24, HPV Type 31: ≥10, HPV Type 33: ≥8, HPV Type 45: ≥8, HPV Type 52: ≥8, and HPV Type 58: ≥8. |
| Percentage of Participants With an Injection-site Adverse Event (AE) | up to 5 days after any vaccination | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site were recorded. |
| Percentage of Participants With a Non-Injection Site (Systemic) AE | up to 15 days after any vaccination | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Systemic AEs were those not categorized as injection-site AEs. |
| Percentage of Participants With a Vaccine-related AE | up to 15 days after any vaccination | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Adverse experience that is judged by the Investigator to be definitely related, probably related, or possibly related to the study drug is defined as a vaccine-related AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine | 4 weeks post-vaccination 3 (Month 7) | Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using cLIA. Titers are reported in milli Merck Units/mL. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Enrolled 9-valent human papillomavirus (9vHPV) L1 VLP vaccine, 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. | 100 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Enrolled |
|---|---|
| Age, Continuous | 11.7 years STANDARD_DEVIATION 1.7 |
| Sex: Female, Male Female | 100 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 96 / 100 |
| serious Total, serious adverse events | 0 / 100 |
Outcome results
Primary
Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine
Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using competitive luminex immunoassay (cLIA). The serostatus cutoffs (milli Merck U/mL) for HPV types were as follows: HPV Type 6: ≥30, HPV Type 11: ≥16; HPV Type 16: ≥20, HPV Type 18: ≥24, HPV Type 31: ≥10, HPV Type 33: ≥8, HPV Type 45: ≥8, HPV Type 52: ≥8, and HPV Type 58: ≥8.
Time frame: 4 weeks post-vaccination 3 (Month 7)
Population: Participants who received all 3 vaccinations and met criteria for Per Protocol Immunogenicity (PPI) Population (not a general protocol violator, received all vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range) for at least 1 of the 9 HPV types.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Enrolled | Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine | Anti-HPV 6 (n=97) | 100 Percentage of Participants |
| All Enrolled | Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine | Anti-HPV 11 (n=97) | 100 Percentage of Participants |
| All Enrolled | Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine | Anti-HPV 16 (n=99) | 100 Percentage of Participants |
| All Enrolled | Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine | Anti-HPV 18 (n=98) | 100 Percentage of Participants |
| All Enrolled | Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine | Anti-HPV 31 (n=97) | 100 Percentage of Participants |
| All Enrolled | Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine | Anti-HPV 33 (n=98) | 100 Percentage of Participants |
| All Enrolled | Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine | Anti-HPV 45 (n=99) | 100 Percentage of Participants |
| All Enrolled | Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine | Anti-HPV 52 (n=99) | 100 Percentage of Participants |
| All Enrolled | Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine | Anti-HPV 58 (n=95) | 100 Percentage of Participants |
Primary
Percentage of Participants With an Injection-site Adverse Event (AE)
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site were recorded.
Time frame: up to 5 days after any vaccination
Population: Safety Population, which consisted of all participants who received at least one vaccination and had available follow-up data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Enrolled | Percentage of Participants With an Injection-site Adverse Event (AE) | 95.0 Percentage of Participants |
Primary
Percentage of Participants With a Non-Injection Site (Systemic) AE
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Systemic AEs were those not categorized as injection-site AEs.
Time frame: up to 15 days after any vaccination
Population: Safety Population, which consisted of all participants who received at least one vaccination and had available follow-up data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Enrolled | Percentage of Participants With a Non-Injection Site (Systemic) AE | 35.0 Percentage of Participants |
Primary
Percentage of Participants With a Vaccine-related AE
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Adverse experience that is judged by the Investigator to be definitely related, probably related, or possibly related to the study drug is defined as a vaccine-related AE.
Time frame: up to 15 days after any vaccination
Population: Safety Population, which consists of all participants who received at least one vaccination and had available follow-up data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Enrolled | Percentage of Participants With a Vaccine-related AE | 96.0 Percentage of Participants |
Secondary
Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine
Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using cLIA. Titers are reported in milli Merck Units/mL.
Time frame: 4 weeks post-vaccination 3 (Month 7)
Population: Participants who received all 3 vaccinations and met criteria for Per Protocol Immunogenicity (PPI) Population (not a general protocol violator, received all vaccinations within acceptable day ranges, seronegative at Day 1 for HPV type(s), and had a Month 7 serum sample collected within an acceptable day range) for at least 1 of the 9 HPV types.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| All Enrolled | Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine | Anti-HPV 52 (n=99) | 1069.1 milli Merck units/mL |
| All Enrolled | Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine | Anti-HPV 58 (n=95) | 1488.2 milli Merck units/mL |
| All Enrolled | Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine | Anti-HPV 6 (n=97) | 1836.5 milli Merck units/mL |
| All Enrolled | Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine | Anti-HPV 11 (n=97) | 1331.3 milli Merck units/mL |
| All Enrolled | Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine | Anti-HPV 16 (n=99) | 6823.6 milli Merck units/mL |
| All Enrolled | Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine | Anti-HPV 18 (n=98) | 2159.9 milli Merck units/mL |
| All Enrolled | Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine | Anti-HPV 31 (n=97) | 2052.5 milli Merck units/mL |
| All Enrolled | Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine | Anti-HPV 33 (n=98) | 994.8 milli Merck units/mL |
| All Enrolled | Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine | Anti-HPV 45 (n=99) | 811.0 milli Merck units/mL |