Efficacy and Tolerability Study of V501 in Japanese Males (V501-122)

Study Overview
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Brief Summary
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A study to evaluate the efficacy and tolerability of V501 (quadrivalent Human Papilloma Virus [HPV] [Type 6, 11, 16 and 18] L1 Virus-Like Particle vaccine, GARDASIL™) in healthy, 16- to 26-year old Japanese males. The hypotheses tested are: 1) V501 reduces the combined incidence of HPV 6-, 11-, 16-, or 18-related persistent infection compared with placebo, and 2) V501 reduces the combined incidence of HPV 6-, 11-, 16-, or 18-related persistent infection, condyloma acuminata, penile/perianal/perineal intraepithelial neoplasia, or penile, perianal, or perineal cancer compared with placebo.

Official Title
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A Phase III Placebo-controlled Clinical Trial to Study the Tolerability, Immunogenicity and Efficacy of V501 in 16- to 26-year-old Japanese Men

Conditions
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Anogenital Human Papilloma Virus Infection, Condyloma Acuminata

Intervention / Treatment
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* Biological: V501
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese No clinical evidence of gross genital lesion suggesting sexually-transmitted disease and no clinically present external genital warts Other inclusion criteria will be discussed with the investigator during screening Exclusion Criteria: History of known prior vaccination with an HPV vaccine or plans to receive one outside the study History of external genital warts History of severe allergic reaction that required medical intervention Received immune globulin or blood-derived products in the past 6 months or plan 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), 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 and certain regimens of systemic corticosteroids Known thrombocytopenia or coagulation disorder that would contraindicate intramuscular injections Ongoing alcohol or drug abuse within the past 12 months

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 26 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V501<br>Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36. | Biological: V501<br>* Formulated with aluminum hydroxyphosphate sulfate (AAHS) adjuvant<br>* Other names: Quadrivalent HPV (Type 6, 11, 16 and 18) L1 Virus-Like Particle vaccine;|
| Placebo Comparator: Placebo<br>Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36. | Biological: Placebo<br>* Formulated with AAHS adjuvant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Vaccine-related 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. Vaccine-related AEs are those that were deemed possibly, probably, or definitely related to vaccine administration by the investigator. The percentage of participants with a vaccine-related systemic AE was summarized. | Up to 15 days after any vaccination | 
| Combined Incidence of HPV Type 6, 11, 16, or 18-related Persistent Infection | Persistent infection was defined as 1) polymerase chain reaction (PCR) positive to HPV Type 6, 11, 16, or 18 in 2 consecutive anogenital or biopsy samples collected ≥4 months apart, or 2) Pathology Panel consensus diagnosis of condyloma acuminate, penile/perianal/perineal intraepithelial neoplasia (PIN), penile, perianal, or perineal cancer and PCR detection of HPV Type 6, 11, 16, or 18 in an adjacent section and PCR positive for the same HPV type at a separate adjacent visit. The combined incidence of HPV Type 6, 11, 16, or 18 persistent infection detected in samples from ≥2 consecutive visits ≥6 months apart was assessed. | Up to Month 36 | 
| Percentage of Participants With Maximum Temperature ≥37.5°C Reported on the Vaccination Report Card | Body temperature (oral or oral equivalent) was recorded on the Vaccination Report Card (VRC). The percentage of participants with a maximum temperature ≥37.5°C was summarized. | Up to 5 days after any vaccination | 
| Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card | 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 percentage of participants with an injection-site AE prompted on the VRC (erythema, pain, and swelling) was summarized. | Up to 5 days 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 percentage of participants with a systemic AE was summarized. | Up to 15 days after any vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Incidence of HPV Type 6, 11, 16, or 18-related Persistent Infection or Disease | Persistent infection was defined as 1) polymerase chain reaction (PCR) positive to HPV Type 6, 11, 16, or 18 in 2 consecutive anogenital or biopsy samples collected ≥4 months apart, or 2) Pathology Panel consensus diagnosis of condyloma acuminate, penile/perianal/perineal intraepithelial neoplasia (PIN), penile, perianal, or perineal cancer and PCR detection of HPV Type 6, 11, 16, or 18 in an adjacent section and PCR positive for the same HPV type at a separate adjacent visit. The incidence of persistent infection detected in samples from ≥2 consecutive visits ≥6 months apart was assessed. Disease was defined as HPV Type 6, 11, 16, or 18-related condyloma acuminate, PIN, penile, perianal, or perineal cancer. The combined incidence of HPV Type 6, 11, 16, or 18 persistent infection or disease was assessed. | Up to Month 36 |