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

Merck Sharp & Dohme LLC4,065 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

4,065

Conditions

Condylomata Acuminata

Interventions

Eligibility

Sex: MALEMin age: 16 YearsMax age: 26 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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 Outcomes

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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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.

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Month 120