An Investigational Study of Gardasil™ (qHPV Vaccine) in Reducing the Incidence of Anogenital Warts in Young Men (V501-020)

Study Overview
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Brief Summary
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This study was conducted to demonstrate that Gardasil™ (quadrivalent human papillomavirus [qHPV] vaccine) 1) is well tolerated in young men, 2) reduces incidence of external genital lesions in young men, 3) reduces the incidence of anal intraepithelial neoplasia (AIN) or anal cancer in men having sex with men (MSM), and 4) reduces incidence of Human Papillomavirus (HPV) infection in young men. In the 7-month Base Study participants received randomly assigned qHPV vaccine or placebo at Day 1, Month 2, and Month 6. Base Study follow-up continued through Month 36. In Extension 1 (EXT1), participants who received placebo or an incomplete qHPV vaccine regimen in the Base Study were offered qHPV vaccine. Participants were followed in EXT1 for 7 months. In Extension 2 [LTFU (EXT2)], long-term effectiveness, immunogenicity, and safety of qHPV vaccine were followed up to 10 years following study enrollment. Participants who received ≥1 dose of qHPV vaccine in the Base Study or EXT1 were eligible to enroll in LTFU (EXT2).

Official Title
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An Investigational Vaccine in Reducing the Incidence of Anogenital Warts in Young Men

Conditions
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Condylomata Acuminata

Intervention / Treatment
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* Biological: (Gardasil™) human papillomavirus (types 6, 11, 16, 18) recombinant vaccine
* Biological: Comparator: placebo (unspecified)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy heterosexual males between the ages of 16 years and 23 years and 364 days. Healthy men having sex with men (MSM) between the ages of 16 years and 26 years and 364 days. No clinical evidence of genital lesions suggesting sexually-transmitted disease, and no history of anogenital warts Additional criteria will be discussed with you by the physician Exclusion Criteria: Concurrently enrolled in a clinical study involving collection of genital specimens History of known prior vaccination with an HPV vaccine Received an inactivated vaccine within 14 days or a live virus vaccine within 21 days prior to enrollment History of a severe allergic reaction that required medical intervention Received any immune globulin or blood-derived products within 6 months prior to the first study injection History of splenectomy, immune disorders, or receiving immunosuppressives Immunocompromised or diagnosed with HIV infection Known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections History of recent or ongoing alcohol or drug abuse

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: qHPV Vaccine<br>The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36. | Biological: (Gardasil™) human papillomavirus (types 6, 11, 16, 18) recombinant vaccine<br>* 0.5 mL intramuscular injection in the deltoid muscle at Day 1, Month 2, and Month 6 in the Base Study<br>* Other names: V501;|
| Placebo Comparator: Placebo<br>The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received placebo at Day 1, Month 2 and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36. | Biological: Comparator: placebo (unspecified)<br>* 0.5 mL intramuscular injection in the deltoid muscle at Day 1, Month 2, and Month 6 in the Base Study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Base Study: Incidence of Human Papillomavirus (HPV) Type 6/11/16/18-related External Genital Warts, Penile/Perianal/Perineal Intraepithelial Neoplasia (PIN), Penile, Perianal or Perineal Cancer | Participants with HPV 6/11/16/18-related external genital warts, penile/perianal/perineal intraepithelial neoplasia (PIN), penile, perianal or perineal cancer per 100 person-years of follow-up was assessed. | Base study: through Month 36 | 
| Overall Study: Incidence of HPV Type 6/11-related Genital Warts | Incidence of HPV Type 6/11-related genital warts is expressed as events per 10,000 person-years of follow-up. | Up to 10 years after the first dose of qHPV vaccine | 
| Overall Study: Incidence of HPV Type 6/11/16/18-related External Genital Warts, PIN, Penile, Perianal or Perineal Cancer | Incidence of HPV Type 6/11/16/18-related external genital warts, PIN, penile, perianal or perineal cancer is expressed as events per 10,000 person-years of follow-up. | Up to 10 years after the first dose of qHPV vaccine | 
| Overall Study: Incidence of HPV Type 6/11/16/18-related Anal Intraepithelial Neoplasia (AIN) and Anal Cancer | Incidence of HPV Type 6/11/16/18-related AIN and anal cancer is expressed as events per 10,000 person-years of follow-up. MSM is men having sex with men. | Up to 10 years after the first dose of qHPV vaccine | 
| Base Study: Number of Participants With Severe Injection Site Adverse Experiences (AEs) | An adverse event 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. Any worsening of a preexisting condition which is temporally associated with the use of the SPONSOR'S product, is also an adverse experience. A severe AE is incapacitating with inability to work or do usual activities. | Base study: through Day 5 after any vaccination | 
| Base Study: Number of Participants With Vaccine-Related Serious Adverse Events (SAEs) | A serious adverse event is an AE that 1) results in death, 2) is life threatening, 3) results in persistent or significant disability or incapacity, 4) results in or prolongs an existing hospitalization, 5) is a congenital anomaly or birth defect, 6) is a cancer, 7) is an overdose, or 8) based on appropriate medical judgment may jeopardize the participant and may require medical or surgical intervention. A vaccine-related AE is one deemed to be possibly, probably or definitely related to study vaccine by the investigator. | Base study: through Month 36 | 
| LTFU (EXT2): Number of Participants With Vaccine-Related SAEs | An SAE is an AE that 1) results in death, 2) is life threatening, 3) results in persistent or significant disability or incapacity, 4) results in or prolongs an existing hospitalization, 5) is a congenital anomaly or birth defect, 6) is a cancer, 7) is an overdose, or 8) based on appropriate medical judgment may jeopardize the participant and may require medical or surgical intervention. A vaccine-related AE is one deemed to be possibly, probably or definitely related to study vaccine by the investigator. | LTFU (EXT2): Early Vaccination Group: up to 12 years after last dose of qHPV vaccine; LTFU (EXT2) Catch-up Vaccination Group: up to 7 years after last dose of qHPV vaccine | 
| LTFU (EXT2): Number of Participants Who Died | The number of participants who died was assessed. | LTFU (EXT2): Early Vaccination Group: up to 12 years after last dose of qHPV vaccine; LTFU (EXT2) Catch-up Vaccination Group: up to 7 years after last dose of qHPV vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Base Study: Incidence of HPV 6/11/16/18-related Persistent Infection | Participants with HPV Type 6/11/16/18-related persistent infection per 100 person-years of follow-up was assessed. | Base study: through Month 36 | 
| Base Study: Incidence of HPV 6/11/16/18-related Deoxyribonucleic Acid (DNA) Detection | Participants with HPV 6/11/16/18-related DNA detection per 100 person-years of follow-up was assessed. | Base study: through Month 36 | 
| Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 7 Assessed by Competitive Luminex Immunoassay (cLIA) | Antibodies to HPV types were measured using cLIA. Antibody titers were expressed as cLIA milli Merck units/mL (cLIA mMU/mL). | Month 7 | 
| Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 36 Assessed by cLIA | Antibodies to HPV types were measured using cLIA. Antibody titers were expressed as cLIA milli Merck units/mL (cLIA mMU/mL). | Month 36 | 
| Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 72 Assessed by cLIA | Antibodies to HPV types were measured using cLIA. Antibody titers were expressed as cLIA milli Merck units/mL (cLIA mMU/mL). | Month 72 | 
| Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by cLIA | Antibodies to HPV types were measured using cLIA. Antibody titers were expressed as cLIA milli Merck units/mL (cLIA mMU/mL). | Month 120 | 
| Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 7 Assessed by cLIA | Antibodies to HPV types were measured using cLIA. Thresholds for seropositive were ≥20, 16, 20, and 24 cLIA mMU/mL for HPV Types 6, 11, 16, and 18, respectively. | Month 7 | 
| Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 36 Assessed by cLIA | Antibodies to HPV types were measured using cLIA. Thresholds for seropositive were ≥20, 16, 20, and 24 cLIA mMU/mL for HPV Types 6, 11, 16, and 18, respectively. | Month 36 | 
| Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 72 Assessed by cLIA | Antibodies to HPV types were measured using cLIA. Thresholds for seropositive were ≥20, 16, 20, and 24 cLIA mMU/mL for HPV Types 6, 11, 16, and 18, respectively. | Month 72 | 
| Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by cLIA | Antibodies to HPV types were measured using cLIA. Thresholds for seropositive were ≥20, 16, 20, and 24 cLIA mMU/mL for HPV Types 6, 11, 16, and 18, respectively. | Month 120 | 
| Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) | Antibodies to HPV types were measured using Luminex immunoassay (IgG-LIA). The unit of measure for this assay is IgG LIA mMU/mL; this unit cannot be directly compared with the cLIA mMU/mL unit reported for the cLIA results. | Month 120 | 
| Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by IgG LIA | Antibodies to HPV types were measured using IgG LIA. Thresholds for seropositive were ≥9, 6, 5, and 5 IgG LIA mMU/mL for HPV Types 6, 11, 16, and 18, respectively. | Month 120 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anogenital warts