Efficacy Against Oral Persistent Infection, Immunogenicity and Safety of the 9-valent Human Papillomavirus Vaccine (9vHPV) in Men Aged 20-45 Years (V503-049)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, immunogenicity and safety of the 9-valent human papillomavirus (9vHPV) vaccine in men 20 to 45 years of age. The primary hypothesis tested after the primary database lock is that administration of a 3-dose regimen of 9vHPV vaccine will reduce the incidence of HPV 16/18/31/33/45/52/58-related oral persistent infection (6 months or longer) compared with placebo. There will also be an Extension Study to offer an opportunity to complete the 3 dose regimen of 9vHPV vaccine for participants who received placebo in the Base Study, or received less than 3 doses of 9vHPV vaccine in the Base Study.

Official Title
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A Phase 3, International, Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy, Immunogenicity, and Safety of the 9vHPV Vaccine, a Multivalent L1 Virus-like Particle Vaccine, in the Prevention of Oral Persistent Infection With HPV Types 16, 18, 31, 33, 45, 52, or 58 in Adult Males, 20 to 45 Years of Age

Conditions
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Papillomavirus Infections

Intervention / Treatment
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* Biological: 9vHPV Vaccine
* Other: Placebo (Saline for Injection)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Base Study: Is healthy and is judged to be in good physical health based on medical history and physical examination. Has provided written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research. Agrees to provide study personnel with a primary telephone number as well as an alternate means of contact, if available (such as an alternate telephone number or email) for follow-up purposes Can read, understand, and complete the electronic vaccination report card (eVRC). Has had at least 1 lifetime sexual partner. Extension Study: Participants may continue in the Extension Study if Inclusion Criteria #1 and #4 are still met, and the participants was in either the placebo group in the Base Study or the vaccine group in the Base Study but did not complete the vaccination series. Provides documented consent for the Extension Study. Exclusion Criteria: Base Study: Has a history of human papillomavirus (HPV)-related anal lesion (anal intraepithelial neoplasia or anal cancer) or HPV related head and neck cancer. Has a history of or clinical evidence at the Day 1 external genital examination of HPV-related external lesion. Has clinical evidence at the Day 1 external genital examination of gross genital lesion suggesting sexually transmitted disease. Has a fever (defined as oral temperature ≥100.0°F or ≥37.8°C) within a 24-hour period prior to Day 1 visit. Has a history of severe allergic reaction (e.g., swelling of the mouth and throat, difficulty breathing, hypotension, or shock) 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 congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition. Has a history of splenectomy. Has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate by judgment of investigator. Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence at the discretion of the investigator. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems because of alcohol use. Has received within 12 months prior to enrollment, is receiving, or plans to receive during the study, the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (ARAVA®), TNF-α antagonists, monoclonal antibody therapies (including rituximab [RITUXAN®]), intravenous immunoglobulin (IVIG), anti-lymphocyte sera, or other therapy known to interfere with the immune response. Regarding systemic corticosteroids, a participant will be excluded if he is currently receiving steroid therapy, has recently received such therapy, or has received 2 or more courses of high-dose corticosteroids (≥20 mg/day of prednisone [or equivalent] orally or parenterally) lasting at least 1 week in duration in the year prior. Participants using inhaled, nasal, or topical steroids are considered eligible for the study. Has received within the 3 months prior to vaccination, is receiving, or plans to receive during the study, any immune globulin product (including RhoGAM™) or blood-derived product other than IVIG Has received inactivated or recombinant vaccines within 14 days prior to vaccination or receipt of live vaccines within 21 days prior to vaccination Is concurrently enrolled in other clinical studies of investigational agents Has previously received a marketed HPV vaccine, or has participated in a clinical trial for any HPV vaccine (receiving either active agent or placebo) Has engaged in sexual activity 48 hours prior to vaccination. Sexual activity is defined as: penile penetrative vaginal intercourse with female partner; penile penetrative or receptive anal intercourse with male or female partner; or oral sex involving any contact between participant's mouth with a female partner's vagina, genital or anal area or male partner's penis or genital or anal area. This also includes any contact between participant's partner's mouth with participant's penis, genital or anal area. 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. Extension Study: - Participants must be excluded from the Extension Study if Base Study Exclusion Criteria #4, 5, 7, 10, 15, or 18 are met.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 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: 9vHPV vaccine<br>Single 0.5-mL intramuscular injection at Day 1, Month 2, and Month 6 | Biological: 9vHPV Vaccine<br>* 9-valent human papillomavirus vaccine (9vHPV) is an aluminum-adjuvanted recombinant protein vaccine prepared from the highly purified virus-like particles (VLPs) of the recombinant major capsid (L1) protein of HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 given as a 0.5 mL intramuscular injection.<br>* Other names: V503;|
| Placebo Comparator: Placebo<br>Single 0.5-mL intramuscular injection at Day 1, Month 2, and Month 6 | Other: Placebo (Saline for Injection)<br>* 0.9% sodium chloride given as a 0.5-mL intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Human Papillomavirus (HPV)16/18/31/33/45/52/58-related 6-month Persistent Oral Infection | A 6-month persistent infection is defined to have occurred if a participant, after completion of the Month 7 visit, is positive for the same human papillomavirus (HPV) type by the HPV polymerase chain reaction (PCR) assay to at least 1 common gene in Oral Rinse and Gargle (ORG) samples obtained at 2 or more consecutive visits at 6 months (+/-1 month visit window) apart. | Up to Month 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Human Papillomavirus (HPV) 6/11-related 6-month Persistent Oral Infection | A 6-month persistent infection is defined to have occurred if a participant, after completion of the Month 7 visit, is positive for the same human papillomavirus (HPV) type by the HPV polymerase chain reaction (PCR) assay to at least 1 common gene in Oral Rinse and Gargle (ORG) samples obtained at 2 or more consecutive visits at 6 months (+/-1 month visit window) apart. | Up to Month 42 | 
| Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 Antibodies | Serum antibodies to HPV types are measured with competitive Luminex immunoassay (cLIA). Geometric mean titers of antibodies to HPV types will be calculated by exponentiating the mean estimates of natural logarithm of the anti-HPV titers. | 1 month postdose 3 (Month 7) | 
| Percentage of Participants who Seroconvert to Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 | Seroconversion is defined as changing a participant's serostatus from seronegative at Day 1 to seropositive by 4 weeks postdose 3. A participant with anti-HPV competitive Luminex immunoassay (cLIA) titer at or above the serostatus cutoff of the cLIA for a given HPV type is considered seropositive for that HPV type. | 1 month postdose 3 (Month 7) | 
| Percentage of Participants with at Least 1 Solicited Injection-site Adverse Event (AE) | An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study vaccine. An AE can 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 is temporally associated with the study vaccine or protocol-specified procedure is also an AE. Solicited injection-site AEs such as redness/erythema, swelling, and tenderness/pain at the injection site will be recorded. | Up to 5 days after any vaccination | 
| Percentage of Participants with Elevated Temperature (Fever) | Participants are asked to record oral body temperatures. The percentage of participants with elevated temperature (≥37.8°C or 100.0°F) will be assessed. | Up to 5 days after any vaccination | 
| Percentage of Participants Who Report at Least 1 Systemic Adverse Event | An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study vaccine. An AE can 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 is temporally associated with the study vaccine or protocol-specified procedure is also an AE. Systemic AEs are those not categorized as injection-site AEs. | Up to 15 days after any vaccination | 
| Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE) | A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect, or is another important medical event deemed such by medical or scientific judgment. | Up to 15 days after any vaccination | 
| Percentage of Participants who Experience at Least 1 Serious Vaccine-Related Adverse Event | A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect, or is another important medical event deemed such by medical or scientific judgment. An SAE that is considered by an investigator (a qualified physician) to be vaccine-related will be reported during entire study period. | Up to Month 42 |