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

Phase 3

Completed

• Conditions: Condylomata Acuminata
• Interventions: Biological: (Gardasil™) human papillomavirus (types 6, 11, 16, 18) recombinant vaccine

• Registration Number: NCT00090285
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2004-08-25
• Study First Submitted QC: 2004-08-26
• Study First Posted: 2004-08-27
• Study Start: 2004-09-03
• Primary Completion: 2009-07-31
• Disposition First Submitted: 2009-10-07
• Disposition First Submitted QC: 2009-10-07
• Disposition First Posted: 2009-10-12
• Results First Submitted: 2009-10-14
• Results First Submitted QC: 2009-10-14
• Results First Posted: 2009-11-19
• Study Completion: 2017-04-03
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-24
• Last Update Posted: 2018-08-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 4065

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
qHPV Vaccine	(Gardasil™) human papillomavirus (types 6, 11, 16, 18) recombinant vaccine	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.

Primary Outcome Measures

Name	Time	Method
Overall Study: Incidence of HPV Type 6/11-related Genital Warts	Up to 10 years after the first dose of qHPV vaccine	Incidence of HPV Type 6/11-related genital warts is expressed as events per 10,000 person-years of follow-up.
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	Base study: through Month 36	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.
Overall Study: Incidence of HPV Type 6/11/16/18-related External Genital Warts, PIN, Penile, Perianal or Perineal Cancer	Up to 10 years after the first dose of qHPV vaccine	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.
Base Study: Number of Participants With Severe Injection Site Adverse Experiences (AEs)	Base study: through Day 5 after any vaccination	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: Number of Participants With Vaccine-Related Serious Adverse Events (SAEs)	Base study: through Month 36	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.
LTFU (EXT2): Number of Participants Who Died	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	The number of participants who died was assessed.
Overall Study: Incidence of HPV Type 6/11/16/18-related Anal Intraepithelial Neoplasia (AIN) and Anal Cancer	Up to 10 years after the first dose of qHPV vaccine	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.
LTFU (EXT2): Number of Participants With Vaccine-Related SAEs	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	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.

Secondary Outcome Measures

Name	Time	Method
Base Study: Incidence of HPV 6/11/16/18-related Deoxyribonucleic Acid (DNA) Detection	Base study: through Month 36	Participants with HPV 6/11/16/18-related DNA detection per 100 person-years of follow-up was assessed.
Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by cLIA	Month 120	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.
Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 7 Assessed by Competitive Luminex Immunoassay (cLIA)	Month 7	Antibodies to HPV types were measured using cLIA. Antibody titers were expressed as cLIA milli Merck units/mL (cLIA mMU/mL).
Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 36 Assessed by cLIA	Month 36	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.
Base Study: Incidence of HPV 6/11/16/18-related Persistent Infection	Base study: through Month 36	Participants with HPV Type 6/11/16/18-related persistent infection per 100 person-years of follow-up was assessed.
Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 36 Assessed by cLIA	Month 36	Antibodies to HPV types were measured using cLIA. Antibody titers were expressed as cLIA milli Merck units/mL (cLIA mMU/mL).
Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 7 Assessed by cLIA	Month 7	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 72 Assessed by cLIA	Month 72	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.
Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 72 Assessed by cLIA	Month 72	Antibodies to HPV types were measured using cLIA. Antibody titers were expressed as cLIA milli Merck units/mL (cLIA mMU/mL).
Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by cLIA	Month 120	Antibodies to HPV types were measured using cLIA. Antibody titers were expressed as cLIA milli Merck units/mL (cLIA mMU/mL).
Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA)	Month 120	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.
Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by IgG LIA	Month 120	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.