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

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 Overview

• Status: Completed
• Conditions: Condylomata Acuminata
• Intervention / Treatment: Biological: (Gardasil™) human papillomavirus (types 6, 11, 16, 18) recombinant vaccine; Biological: Comparator: placebo (unspecified)

• Study Type: Interventional
• Enrollment (Actual): 4065
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 26 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: qHPV 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.	Biological: (Gardasil™) human papillomavirus (types 6, 11, 16, 18) recombinant vaccine; 0.5 mL intramuscular injection in the deltoid muscle at Day 1, Month 2, and Month 6 in the Base Study; Other Names: V501; qHPV
Placebo Comparator: Placebo; 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); 0.5 mL intramuscular injection in the deltoid muscle at Day 1, Month 2, and Month 6 in the Base Study

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Participants with HPV 6/11/16/18-related AIN or anal cancer per 100 person-years of follow-up was assessed.	Base study: through Month 36

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Doshi P, Bourgeois F, Hong K, Jones M, Lee H, Shamseer L, Spence O, Jefferson T. Adjuvant-containing control arms in pivotal quadrivalent human papillomavirus vaccine trials: restoration of previously unpublished methodology. BMJ Evid Based Med. 2020 Dec;25(6):213-219. doi: 10.1136/bmjebm-2019-111331. Epub 2020 Mar 17.
• Goldstone SE, Giuliano AR, Palefsky JM, Lazcano-Ponce E, Penny ME, Cabello RE, Moreira ED Jr, Baraldi E, Jessen H, Ferenczy A, Kurman R, Ronnett BM, Stoler MH, Bautista O, Das R, Group T, Luxembourg A, Zhou HJ, Saah A. Efficacy, immunogenicity, and safety of a quadrivalent HPV vaccine in men: results of an open-label, long-term extension of a randomised, placebo-controlled, phase 3 trial. Lancet Infect Dis. 2022 Mar;22(3):413-425. doi: 10.1016/S1473-3099(21)00327-3. Epub 2021 Nov 12.
• Tota JE, Giuliano AR, Goldstone SE, Dubin B, Saah A, Luxembourg A, Velicer C, Palefsky JM. Anogenital Human Papillomavirus (HPV) Infection, Seroprevalence, and Risk Factors for HPV Seropositivity Among Sexually Active Men Enrolled in a Global HPV Vaccine Trial. Clin Infect Dis. 2022 Apr 9;74(7):1247-1256. doi: 10.1093/cid/ciab603. Erratum In: Clin Infect Dis. 2023 Jan 04;:
• Goldstone SE, Jessen H, Palefsky JM, Giuliano AR, Moreira ED Jr, Vardas E, Aranda C, Hillman RJ, Ferris DG, Coutlee F, Marshall JB, Vuocolo S, Haupt RM, Guris D, Garner E. Quadrivalent HPV vaccine efficacy against disease related to vaccine and non-vaccine HPV types in males. Vaccine. 2013 Aug 20;31(37):3849-55. doi: 10.1016/j.vaccine.2013.06.057. Epub 2013 Jul 2.
• Palefsky JM, Giuliano AR, Goldstone S, Moreira ED Jr, Aranda C, Jessen H, Hillman R, Ferris D, Coutlee F, Stoler MH, Marshall JB, Radley D, Vuocolo S, Haupt RM, Guris D, Garner EI. HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med. 2011 Oct 27;365(17):1576-85. doi: 10.1056/NEJMoa1010971.
• Giuliano AR, Palefsky JM, Goldstone S, Moreira ED Jr, Penny ME, Aranda C, Vardas E, Moi H, Jessen H, Hillman R, Chang YH, Ferris D, Rouleau D, Bryan J, Marshall JB, Vuocolo S, Barr E, Radley D, Haupt RM, Guris D. Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males. N Engl J Med. 2011 Feb 3;364(5):401-11. doi: 10.1056/NEJMoa0909537. Erratum In: N Engl J Med. 2011 Apr 14;364(15):1481.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2004
• Primary Completion (Actual): July 31, 2009
• Study Completion (Actual): April 3, 2017

Study Registration Dates

• First Submitted: August 25, 2004
• First Submitted That Met QC Criteria: August 26, 2004
• First Posted (Estimate): August 27, 2004

Study Record Updates

• Last Update Posted (Actual): August 23, 2018
• Last Update Submitted That Met QC Criteria: July 24, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: anogenital warts
• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Skin Diseases, Infectious; Warts; Papillomavirus Infections; Skin Diseases, Viral; Tumor Virus Infections; Condylomata Acuminata
• Other Study ID Numbers: V501-020 (Other Identifier: Merck Protocol Number); Formerly-0904HPVHMES; 2004_103; 2004-002945-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://www.merck.com/clinicaltrials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf