Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Condylomata Acuminata

Warts

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Communicable Diseases

Papillomavirus Infections

Virus Diseases

DNA Virus Infections

Skin Diseases

Skin Diseases, Viral

Tumor Virus Infections

Genital Diseases

Urogenital Diseases

Skin Diseases, Infectious

All Drugs and Chemicals

Vaccines

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.

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.

0.5 mL intramuscular injection in the deltoid muscle at Day 1, Month 2, and Month 6 in the Base Study

(Gardasil™) human papillomavirus (types 6, 11, 16, 18) recombinant vaccine

Comparator: placebo (unspecified)

Medical Monitor

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).

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

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

http://www.merck.com/clinicaltrials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

Participants with HPV 6/11/16/18-related AIN or anal cancer per 100 person-years of follow-up was assessed.

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.

Incidence of HPV Type 6/11-related genital warts is expressed as events per 10,000 person-years of follow-up.

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.

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.

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.

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.

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.

The number of participants who died was assessed.

Participants with HPV Type 6/11/16/18-related persistent infection per 100 person-years of follow-up was assessed.

Participants with HPV 6/11/16/18-related DNA detection per 100 person-years of follow-up was assessed.

Antibodies to HPV types were measured using cLIA. Antibody titers were expressed as cLIA milli Merck units/mL (cLIA mMU/mL).

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.

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.

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.

Merck Sharp & Dohme LLC

Medical Dictionary for Regulatory Activities (MedDRA) version 12.0 was used during the base study and follow-up, MedDRA version 14.1 was used during EXT1, and MedDRA version 20.0 was used during LTFU (EXT2).

Participants at risk in EXT1 received ≥1 qHPV vaccination in EXT1 and had follow-up data.

Other AEs were not solicited during EXT1 or LTFU (EXT2).

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.

qHPV Vaccine: Base Study

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.

Placebo: Base Study

Participants who received placebo and participants who received only 1 dose of qHPV vaccine in the base study were offered a complete 3-dose qHPV vaccine regimen (administered at EXT1 Day 1, Month 2 and Month 6). Participants who received only 2 doses of qHPV vaccine in the base study were offered a single additional dose of qHPV vaccine (administered at EXT1 Day 1).

qHPV Vaccine: EXT1

Participants received ≥1 dose of qHPV vaccine in Base Study, or received placebo in Base Study and qHPV vaccine in EXT1. This arm includes both groups enrolled in LTFU (EXT2): Early Vaccination Group and Catch-up Vaccination Group.

LTFU (EXT2)

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.

qHPV Vaccine in Base Study

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.

Placebo in Base Study

Total

Age, Continuous

Although the upper age limit for this study was 26 years old, one subject age 27 was randomized into the study.

Sex: Female, Male

Asian

Black

Hispanic American

Native American

White

Multi-Racial

Indian (subcontinent)

Polynesian

Race/Ethnicity, Customized

Vice President, Late Stage Development Group Leader

Participants must have received 3 doses of qHPV vaccine or placebo, have no protocol violations that could interfere with the effects of the vaccine, be seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, and must provide data after Month 7.

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

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.

Participants must have received 3 doses of qHPV vaccine, have no protocol violations that could interfere with the effects of the vaccine, be seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, and must provide data after Month 7. This endpoint applied only to participants in the Base Study qHPV vaccine group.

Overall Study: Incidence of HPV Type 6/11-related Genital Warts

Overall Study: Incidence of HPV Type 6/11/16/18-related External Genital Warts, PIN, Penile, Perianal or Perineal Cancer

MSM qHPV Vaccine in Base Study

Participants must have received 3 doses of qHPV vaccine, have no protocol violations that could interfere with the effects of the vaccine, be seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, and must provide data after Month 7. This endpoint applied only to MSM in the Base Study qHPV vaccine group.

Overall Study: Incidence of HPV Type 6/11/16/18-related Anal Intraepithelial Neoplasia (AIN) and Anal Cancer

The analysis population included all vaccinated participants excluding 6 participants who received non-compliant mixed regimens of qHPV vaccine and placebo.

Base Study: Number of Participants With Severe Injection Site Adverse Experiences (AEs)

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. The at-risk population was participants who received ≥ 1 qHPV vaccination in the base study.

qHPV Vaccine: Base Study and Followup

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. The at-risk population was participants who received ≥ 1 placebo injection in the base study.

Placebo: Base Study and Followup

Base Study: Number of Participants With Vaccine-Related Serious Adverse Events (SAEs)

Participants received ≥1 dose of qHPV vaccine in Base Study and were followed up to a total of 10 years after their first dose of qHPV vaccine. No vaccinations were administered during Long-term Follow-up (LTFU) (EXT2).

LTFU (EXT2): Early Vaccination Group

Participants received placebo in Base Study and qHPV vaccine in EXT1 and were followed up to a total of 7 years after their first dose of qHPV vaccine. No vaccinations were administered during LTFU (EXT2).

LTFU (EXT2): Catch-up Vaccination Group

The population analyzed was all randomized participants receiving at least 1 dose of qHPV vaccine in the Base Study or EXT1 and enrolled in LTFU (EXT2).

LTFU (EXT2): Number of Participants With Vaccine-Related SAEs

LTFU (EXT2): Number of Participants Who Died

Only a subset of participants was included for this sub-study. Participants must have received 3 doses of qHPV vaccine or placebo, have no protocol violations that could interfere with the effects of the vaccine, be seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, and must provide data after Month 7.

Base Study: Substudy to Evaluate the Incidence of HPV 6/11/16/18-related Anal Intraepithelial Neoplasia (AIN) and Anal Cancer in Men Having Sex With Men (MSM)

Base Study: Incidence of HPV 6/11/16/18-related Persistent Infection

Base Study: Incidence of HPV 6/11/16/18-related Deoxyribonucleic Acid (DNA) Detection

HPV Type 6

HPV Type 11

HPV Type 16

HPV Type 18

All participants who 1) were seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, 2) received all 3 vaccinations, and 3) did not have protocol deviations that could interfere with the effects of the vaccine. Immunogenicity was assessed only for participants who received qHPV vaccine in the Base Study.

Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 7 Assessed by Competitive Luminex Immunoassay (cLIA)

Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 36 Assessed by cLIA

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 was through Month 36 and for LTFU (EXT2) was through Month 120.

Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 72 Assessed by cLIA

Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by cLIA

Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 7 Assessed by cLIA

Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 36 Assessed by cLIA

Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 72 Assessed by cLIA

Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by cLIA

Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA)

All participants who 1) were seronegative at Day 1 and PCR negative Day 1 through Month 7 for the relevant HPV type, 2) received all 3 vaccinations, and 3) did not have protocol deviations that could interfere with the effects of the vaccine. Immunogenicity was assessed only for participants who received qHPV vaccine in the Base Study..

Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by IgG LIA

The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received quadrivalent human papillomavirus (qHPV) vaccination at Day 1, Month 2 and Month 6.

Follow-up for the Base Study encompassed Month 7 through Month 36.

Participants in the placebo arm in the base study were offered 3 doses of open-label qHPV vaccine at Extension 1 (EXT1) Day 1, Month 2 and Month 6.

Participants were followed to EXT1 Month 7.

EXT1: Placebo in Base Study

Participants who received only 1 dose of qHPV vaccine in the Base Study were offered a complete 3-dose qHPV vaccine regimen (administered at EXT1 Day 1, Month 2 and Month 6). Participants who received only 2 doses of qHPV vaccine in the Base Study were offered a single additional dose of qHPV vaccine (administered at EXT1 Day 1).

Participants were followed to EXT1 Month 7.

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