Immunogenicity and Safety of the 9-valent Human Papillomavirus (9vHPV) Vaccine in Japanese Boys and Girls (V503-066)

Study Overview
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Brief Summary
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The primary objective of this study is the estimation of the human papillomavirus (HPV) 6, 11, 16, 18, 31, 33, 45, 52 and 58 seroconversion at 1 month post last dose (Month 7) following 3 doses and 2 doses of the 9vHPV vaccine. No hypothesis will be tested since this study is an estimation-only study.

Official Title
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A Phase 3, Open-label Clinical Study to Evaluate the Immunogenicity and Safety of 9vHPV Vaccine, in Japanese Boys and Girls, 9 to 15 Years of Age.

Conditions
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Papillomavirus Infections

Intervention / Treatment
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* Biological: 9vHPV vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is Japanese male or female. Is aged at the time of providing the documented informed consent (inclusive): (3-dose boy arm) male from 9 years to 15 years old, (2-dose boy arm) male from 9 years to 14 years old, or (2-dose girl arm) female from 9 years to 14 years old. Has a legally acceptable representative who can read, understand and complete the vaccination report card (VRC). Has not yet had coitarche and does not plan on becoming sexually active during the Day 1 through Month 7. Exclusion Criteria: Has a fever (defined as oral temperature ≥37.5°C) within the 24-hour period prior to the Day 1 visit. Has a history of severe allergic reaction that required medical intervention. Is allergic to any vaccine component, including aluminum, yeast, or Benzonase™. Has known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections. Is currently 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 auto immune condition. Has a history of splenectomy. Has a history of genital warts or positive test for human papillomavirus (HPV). Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within 12 months) of drug or alcohol abuse or dependence at the discretion of the investigator. . Has received within 12 months prior to enrollment, is receiving, or plans to receive during Day 1 through Month 7 of the study, any study-prohibited concomitant immunosuppressive therapy . Has received within the 3 months prior to the Day 1 vaccination, is receiving, or plans to receive during Day 1 through Month 7 of the study, any immune globulin product or blood-derived product other than intravenous gamma globulin (IVIG). Has received inactivated or recombinant vaccines within 14 days prior to Day 1 vaccination or receipt of live vaccines within 28 days prior to Day 1 vaccination. Has previously received a marketed HPV vaccine or has participated in a clinical trial for any HPV vaccine (receiving either active agent or placebo). Is concurrently enrolled in other clinical studies of investigational agents. Is unlikely to adhere to the study procedures, keep appointments, or is planning to permanently relocate from the area prior to the completion of the study or to leave for an extended period when study visits would need to be scheduled. 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.

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3-dose in 9 to 15 year old boys<br>9 to 15 year old boys will receive a 3-dose regimen of 9-valent human papillomavirus (9vHPV) vaccine (Day 1, Month 2 and Month 6). | Biological: 9vHPV vaccine<br>* 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>* Other names: GARDASIL™9;|
| Experimental: 2-dose in 9 to 14 year old boys<br>9 to 14 year old boys receive a 2-dose regimen of 9vHPV vaccine (Day 1 and Month 6). | Biological: 9vHPV vaccine<br>* 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>* Other names: GARDASIL™9;|
| Experimental: 2-dose in 9 to 14 year old girls<br>9 to 14 year old girls receive a 2-dose regimen of 9vHPV vaccine (Day 1 and Month 6). | Biological: 9vHPV vaccine<br>* 9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) administered as a 0.5-mL intramuscular injection<br>* Other names: GARDASIL™9;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion Percentages for the HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 | Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 will be determined using competitive Luminex Immunoassay (cLIA). Seroconversion is defined as changing serostatus from seronegative at Day 1 to seropositive at 4 weeks post last vaccination. | 4 weeks post last vaccination (Month 7) | 
| Percentage of Participants With at Least 1 Solicited Injection-site Adverse Event | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with solicited injection-site AEs (erythema/redness, pain and swelling) will be assessed. | Up to 5 days post vaccination | 
| Percentage of Participants With at Least 1 Systemic Adverse Event | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with a systemic AE will be assessed. | Up to 15 days post vaccination | 
| Percentage of Participants With at Least 1 Serious Adverse Event | A serious adverse event (SAE) is defined as one that results in death, is life threatening, or requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or other important medical event that may require medical intervention. | Up to  Month 30 | 
| Percentage of Participants With at Least 1 Vaccine-related Serious Adverse Event | A serious adverse event (SAE) is defined as one that results in death, is life threatening, or requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or other important medical event that may require medical intervention. An SAE that is judged by the investigator to be related to the study vaccine is defined as a vaccine-related SAE. | Up to  Month 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers of Anti-HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 | Serum antibodies to HPV types 6, 11, 16, 18 31, 33, 45, 52, and 58 will be measured with a cLIA. Titers are reported in milli Merck Units/mL. | 4 weeks post last vaccination (Month 7) |