Safety and Tolerability Study of V501 in Japanese Boys (V501-200)

Study Overview
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Brief Summary
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This is a study of V501 [quadrivalent Human Papillomavirus (HPV) (Type 6, 11, 16 and 18) L1 virus-like particle (VLP) vaccine] in healthy Japanese boys. This study will consist of two periods. Period I of the study is to evaluate the immunogenicity and tolerability of V501 up to Month 7. Period II of the study is to evaluate the long-term immunogenicity and safety from Month 7 to Month 30. Two analyses are planned. The first analysis will be conducted when all subjects have completed their Month 7 visit or have been discontinued before that time. The second analysis will be conducted at the end of study. The primary hypothesis tested in this study is that seroconversion rates for the vaccine HPV types will be >90% at 4 weeks postdose 3.

Official Title
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A Phase III, Open-Label, Clinical Trial to Study the Safety and Immunogenicity of the Quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP Particle (VLP) Vaccine in 9- to 15-Year-Old Japanese Boys

Conditions
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Condyloma Acuminata, Anogenital Human Papilloma Virus Infection

Intervention / Treatment
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* Biological: V501


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Japanese male Have a legal representative who provides written informed consent for the trial on the participant's behalf Have a legal representative who is able to read, understand, and complete the vaccine report card Has not yet had coitarche and does not plan on becoming sexually active from Day 1 through Month 7 of the study Other inclusion criteria will be discussed with the investigator during screening Exclusion Criteria: Currently enrolled in clinical studies of investigational agents History of known prior vaccination with an HPV vaccine or plans to receive one outside the study History of severe allergic reaction that required medical intervention Allergic to any vaccine component, including aluminum, yeast, or BENZONASE™ Received immune globulin or blood-derived products in the past 6 months or plans to receive any before Month 7 of the study History of splenectomy, is currently immunocompromised, or has been diagnosed with immunodeficiency, Human Immunodeficiency Virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition Received immunosuppressive therapy in the past year, excluding inhaled, nasal, or topical corticosteroids Known thrombocytopenia or coagulation disorder that would contraindicate intramuscular injections Ongoing alcohol or drug abuse within the past 12 months History of genital warts or a positive test for HPV

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

Sexes Eligible for Study
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Male

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V501<br>0.5 mL intramuscular injection on Day 1, Month 2, and Month 6 | Biological: V501<br>* Quadrivalent HPV [Type 6, 11, 16 and 18] L1 VLP vaccine), 0.5 mL intramuscular injection on Day 1, Month 2, and Month 6<br>* Other names: Gardasil™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18 | Antibodies to HPV Types 6, 11, 16, and 18 were measured using a competitive luminex immunoassay 4 weeks after 3rd vaccination (Month 7). Antibody titers were expressed as milli Merck units/mL (mMU/mL). Seroconversion was defined as an anti-HPV 6 titer ≥20 mMU/mL, an anti-HPV 11 titer ≥16 mMU/mL, an anti-HPV 16 titer of ≥20 mMU/mL and an anti-HPV 18 titer of ≥24 mMU/mL. | Four weeks postdose 3 (Month 7) | 
| Percentage of Participants With Elevated Oral Temperature (>=37.5° C) | The parent/guardian of the participant was to record the participant's oral temperature in the evening after each study vaccination and daily for 4 days after each study vaccination. Elevated temperature was defined as ≥99.5°F (≥37.5ºC). The percentage of participants that had an elevated temperature was summarized. | Up to Day 5 after any vaccination | 
| Percentage of Participants With an Injection-site Adverse Event | An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study drug. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study drug or protocol-specified procedure is also an AE. The parent/guardian of the participant was 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. | Up to Day 5 after any vaccination | 
| Percentage of Participants With a Systemic Adverse Event | An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study drug. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study drug or protocol-specified procedure is also an AE. The parent/guardian of the participant was to record the presence of any VRC-prompted systemic AEs that occurred in the 5 days after any vaccination. The percentage of participants with a systemic AE was summarized. | Up to Day 15 after any vaccination | 
| Percentage of Participants With a Serious Adverse Event | 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 sponsor's product, whether or not considered related to the use of the product. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event. The percentage of participants that experienced 1 or more SAEs was summarized. | Up to Day 15 after any vaccination | 
| Percentage of Participants With a Vaccine-related Serious Adverse Event | 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 sponsor's product, whether or not considered related to the use of the product. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event. The percentage of participants that experienced 1 or more SAEs that were considered at least possibly related to the study vaccine was summarized. | Up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18 Participants Aged 9 to 15 Years Versus Participants Aged 16 to 26 Years | Antibodies to HPV Types 6, 11, 16, and 18 were measured using a competitive luminex immunoassay. Antibody titers were expressed mMU/mL. GMTs obtained for each anti-HPV from this study were compared to each of the ant-HPV GMTs obtained in study V501-122 (NCT NCT01862874) in which Japanese males 16 to 26 years received V501 in the same 3 dose regimen, to test a hypothesis that would demonstrate non-inferiority. | Four weeks postdose 3 (Month 7) | 
| Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: Persistence at 18 Months | Antibodies to HPV Types 6, 11, 16, and 18 were measured using a competitive luminex immunoassay. Antibody titers were expressed as mMU/mL. | 12 months postdose 3 (18 months) | 
| Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: Persistence at 30 Months | Antibodies to HPV Types 6, 11, 16, and 18 were measured using a competitive luminex immunoassay. Antibody titers were expressed as mMU/mL. | 24 months postdose 3 (30 months) | 
| Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: Persistence at 18 Months | Serum antibodies to HPV types were measured with a competitive luminex immunoassay. The serostatus cutoffs (mMU/mL) for HPV types were as follows: HPV Type 6: ≥20; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24 | 12 months postdose 3 (18 months) | 
| Percentage of Participants With Seroconversion for HPV Types 6, 11, 16, and 18: Persistence at 30 Months | Serum antibodies to HPV types were measured with a competitive luminex immunoassay. The serostatus cutoffs (mMU/mL) for HPV types were as follows: HPV Type 6: ≥20; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24. | 24 months postdose 3 (30 months) |