Adenocarcinoma in Situ, Condylomata Acuminata, Papillomavirus Infections, Uterine Cervical Neoplasms, Vaginal Neoplasms, Vulvar Neoplasms
Conditions
Brief summary
This study will evaluate the safety and immunogenicity of V503 (GARDASIL™9, 9vHPV vaccine) administered to 9- to 26-year-old females and males in Vietnam. The study hypothesis states that V503 induces acceptable anti-human papillomavirus (HPV) 6, 11, 16, 18, 31, 33, 45, 52, and 58 seroconversion at 4 weeks postdose 3.
Interventions
BIOLOGICAL9vHPV vaccine
9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine in a 0.5-mL intramuscular injection
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
9 Years to 26 Years
Healthy volunteers
Yes
Inclusion criteria
* In good physical health * Participants 9 to 15 years of age: has not had coitarche and do not plan on becoming sexually active during the study * Participants 16 to 26 year of age: has never had Papanicolaou (Pap) testing or has had only normal Pap test results. Has a lifetime history of ≤4 male and/or female sexual partners. * Female participants 16 to 26 years of age: has not had sex with males or has had sex with males and used effective contraception, and understands and agrees that during the study she should not have sexual intercourse with males without effective contraception (rhythm method, withdrawal, and emergency contraception are not acceptable methods of contraception per-protocol).
Exclusion criteria
* Known allergy to any vaccine component, including aluminum, yeast, or BENZONASE™ * History of severe allergic reaction that required medical intervention * Has thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections * Concurrently enrolled in clinical studies of investigational agents * Immunocompromised or has been diagnosed with 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 * Had a splenectomy * User of recreational or illicit drugs or has had a recent history (within the last year) of drug abuse or dependence. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems as a result of alcohol use. * History of a positive test for HPV * Male participants 16 to 26 years of age: history of HPV-related external genital lesions (e.g., condyloma acuminata) or HPV-related anal lesions (e.g., condyloma acuminata, or anal intraepithelial neoplasia) or anal cancer. * Female participants 16 to 26 years of age: history of an abnormal cervical biopsy result (showing cervical intraepithelial neoplasia or worse). * Female participants 16 to 26 years of age: history of HPV-related external genital lesions (e.g., condyloma acuminata, or vulvar intraepithelial neoplasia) or external genital cancer, HPV-related vaginal lesions (e.g., condyloma acuminata, or vaginal intraepithelial neoplasia) or vaginal cancer, or HPV-related anal lesions (e.g., condyloma acuminata, or anal intraepithelial neoplasia) or anal cancer. * Female participants: pregnant as determined by a serum pregnancy test or urine pregnancy test that is sensitive to 25 mIU/mL beta human chorionic gonadotropin (β-hCG). * Female participants: expecting to donate eggs during the study. * Receiving or has received a prohibited immunosuppressive therapy in the year prior to the study * Received any immune globulin product or blood-derived product within the 3 months prior to the Day 1 vaccination, or plans to receive any such product during the study * Received inactivated or recombinant vaccines within 14 days prior to the Day 1 vaccination or has received live vaccines within 21 days prior to the Day 1 vaccination * Received a marketed HPV vaccine, or has participated in an HPV vaccine clinical study and has received either active agent or placebo * Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | 4 weeks postdose 3 (Month 7) | Seroconversion was defined as a participant who was anti-HPV seronegative at Day 1 and became seropositive at 4 weeks postdose 3 (Month 7). Anti-HPV antibodies were measured using a Competitive Luminex Immunoassay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Solicited Injection-site Adverse Event | Up to 5 days after any vaccination | An adverse event (AE) was defined as any untoward medical occurrence in a participant which did not necessarily have a causal relationship with study vaccine. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the study vaccine or protocol-specified procedure was also an AE. The participant or the parent/guardian of the participant were to record the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 5 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (erythema, pain, and swelling) was summarized. |
| Percentage of Participants With a Solicited Systemic Adverse Event | Up to 5 days after any vaccination | An AE was defined as any untoward medical occurrence in a participant which did not necessarily have a causal relationship with study vaccine. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the study vaccine or protocol-specified procedure was also an AE. The only solicited systemic AE was in response to results of daily oral temperature assessments. The participant or the parent/guardian of the participant will be asked to record the participant's oral temperature in the evening after each study vaccination and daily for 4 days after each study vaccination on VRC. The percentage of participants that had an AE due to an elevated oral temperature \[(≥ 37.8 °C (100.0 °F)\] was summarized. |
| Percentage of Participants With a Vaccine-related Serious Adverse Event | Up to 4 weeks postdose 3 (Month 7) | A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants that experience at least one SAE that was reported as at least possibly related to the study vaccine was summarized. |
| Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 | Day 1 (predose) | Anti-HPV Type 6, 11, 16, 18, 31, 33, 45, 52, and 58 antibodies are measured using a Competitive Luminex Immunoassay. Titers are reported in milli Merck units/mL (mMU/mL). |
| Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | 4 weeks postdose 3 (Month 7) | Anti-HPV Type 6, 11, 16, 18, 31, 33, 45, 52, and 58 antibodies are measured using a Competitive Luminex Immunoassay. Titers are reported in mMU/mL. |
Countries
Vietnam
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 9vHPV Vaccine Participants received a single 0.5-mL intramuscular injection of the 9vHPV vaccine at Day 1, Month 2, and Month 6 | 201 |
| Total | 201 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | 9vHPV Vaccine |
|---|---|
| Age, Continuous | 15.8 years STANDARD_DEVIATION 4.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 201 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 201 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 135 Participants |
| Sex: Female, Male Male | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 201 |
| other Total, other adverse events | 90 / 200 |
| serious Total, serious adverse events | 1 / 200 |
Outcome results
Primary
Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7
Seroconversion was defined as a participant who was anti-HPV seronegative at Day 1 and became seropositive at 4 weeks postdose 3 (Month 7). Anti-HPV antibodies were measured using a Competitive Luminex Immunoassay.
Time frame: 4 weeks postdose 3 (Month 7)
Population: All allocated participants who were seronegative to the appropriate HPV type at Day 1, received all 3 vaccinations with the correct dose within acceptable day ranges, provided a serum sample within 21 to 49 days postdose 3, and had no protocol deviations that could interfere with the evaluation of participant's immune response to 9vHPV vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 9vHPV Vaccine | Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 6 | 100 Percentage of Participants |
| 9vHPV Vaccine | Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 11 | 100 Percentage of Participants |
| 9vHPV Vaccine | Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 58 | 100.0 Percentage of Participants |
| 9vHPV Vaccine | Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 16 | 100 Percentage of Participants |
| 9vHPV Vaccine | Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 18 | 100.0 Percentage of Participants |
| 9vHPV Vaccine | Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 31 | 100.0 Percentage of Participants |
| 9vHPV Vaccine | Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 33 | 100.0 Percentage of Participants |
| 9vHPV Vaccine | Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 45 | 100.0 Percentage of Participants |
| 9vHPV Vaccine | Seroconversion Percentages to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 52 | 100.0 Percentage of Participants |
Secondary
Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7
Anti-HPV Type 6, 11, 16, 18, 31, 33, 45, 52, and 58 antibodies are measured using a Competitive Luminex Immunoassay. Titers are reported in mMU/mL.
Time frame: 4 weeks postdose 3 (Month 7)
Population: All allocated participants who were seronegative to the appropriate HPV type at Day 1, received all 3 vaccinations with the correct dose within acceptable day ranges, provided a serum sample within 21 to 49 days postdose 3, and had no protocol deviations that could interfere with the evaluation of participant's immune response to 9vHPV vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 9vHPV Vaccine | Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 31 | 1137.9 mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 33 | 507.8 mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 45 | 579.2 mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 6 | 1008.2 mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 11 | 796.3 mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 16 | 4605.4 mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 18 | 1621.6 mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 52 | 500.8 mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Antibodies to HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 | Anti-HPV 58 | 701.8 mMU/mL |
Secondary
Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1
Anti-HPV Type 6, 11, 16, 18, 31, 33, 45, 52, and 58 antibodies are measured using a Competitive Luminex Immunoassay. Titers are reported in milli Merck units/mL (mMU/mL).
Time frame: Day 1 (predose)
Population: All allocated participants who were seronegative to the appropriate HPV type at Day 1, received all 3 vaccinations with the correct dose within acceptable day ranges, provided a serum sample within 21 to 49 days postdose 3, and had no protocol deviations that could interfere with the evaluation of participant's immune response to 9vHPV vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 9vHPV Vaccine | Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 | Anti-HPV 45 | NA mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 | Anti-HPV 52 | NA mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 | Anti-HPV 58 | NA mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 | Anti-HPV 6 | NA mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 | Anti-HPV 11 | NA mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 | Anti-HPV 16 | NA mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 | Anti-HPV 18 | 29.3 mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 | Anti-HPV 31 | NA mMU/mL |
| 9vHPV Vaccine | Geometric Mean Titers of Serotype-specific Antibodies: Predose Day 1 | Anti-HPV 33 | NA mMU/mL |
Secondary
Percentage of Participants With a Solicited Injection-site Adverse Event
An adverse event (AE) was defined as any untoward medical occurrence in a participant which did not necessarily have a causal relationship with study vaccine. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the study vaccine or protocol-specified procedure was also an AE. The participant or the parent/guardian of the participant were to record the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 5 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (erythema, pain, and swelling) was summarized.
Time frame: Up to 5 days after any vaccination
Population: All participants that received at least 1 vaccination with 9vHPV vaccine and provided safety data at any time during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 9vHPV Vaccine | Percentage of Participants With a Solicited Injection-site Adverse Event | 45.0 Percentage of Participants |
Secondary
Percentage of Participants With a Solicited Systemic Adverse Event
An AE was defined as any untoward medical occurrence in a participant which did not necessarily have a causal relationship with study vaccine. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the study vaccine or protocol-specified procedure was also an AE. The only solicited systemic AE was in response to results of daily oral temperature assessments. The participant or the parent/guardian of the participant will be asked to record the participant's oral temperature in the evening after each study vaccination and daily for 4 days after each study vaccination on VRC. The percentage of participants that had an AE due to an elevated oral temperature \[(≥ 37.8 °C (100.0 °F)\] was summarized.
Time frame: Up to 5 days after any vaccination
Population: All participants that received at least 1 vaccination with 9vHPV vaccine and provided safety data at any time during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 9vHPV Vaccine | Percentage of Participants With a Solicited Systemic Adverse Event | 0.0 Percentage of Participants |
Secondary
Percentage of Participants With a Vaccine-related Serious Adverse Event
A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants that experience at least one SAE that was reported as at least possibly related to the study vaccine was summarized.
Time frame: Up to 4 weeks postdose 3 (Month 7)
Population: All participants that received at least 1 vaccination with 9vHPV vaccine and provided safety data at any time during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 9vHPV Vaccine | Percentage of Participants With a Vaccine-related Serious Adverse Event | 0.0 Percentage of Participants |