Back to resultsAn Investigational Study of Gardasil™ (qHPV Vaccine) in Reducing the Incidence of Anogenital Warts in Young Men (V501-020)
Primary Purpose
Condylomata Acuminata
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
(Gardasil™) human papillomavirus (types 6, 11, 16, 18) recombinant vaccine
Comparator: placebo (unspecified)
Sponsored by
About this trial
This is an interventional prevention trial for Condylomata Acuminata focused on measuring anogenital warts
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
qHPV Vaccine
Placebo
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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: 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.
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): Number of Participants Who Died
The number of participants who died was assessed.
Secondary Outcome Measures
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: 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.
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).
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).
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).
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).
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00090285
Brief Title
An Investigational Study of Gardasil™ (qHPV Vaccine) in Reducing the Incidence of Anogenital Warts in Young Men (V501-020)
Official Title
An Investigational Vaccine in Reducing the Incidence of Anogenital Warts in Young Men
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
September 3, 2004 (Actual)
Primary Completion Date
July 31, 2009 (Actual)
Study Completion Date
April 3, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Condylomata Acuminata
Keywords
anogenital warts
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
4065 (Actual)
8. Arms, Groups, and Interventions
Arm Title
qHPV Vaccine
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
(Gardasil™) human papillomavirus (types 6, 11, 16, 18) recombinant vaccine
Other Intervention Name(s)
qHPV, V501
Intervention Description
0.5 mL intramuscular injection in the deltoid muscle at Day 1, Month 2, and Month 6 in the Base Study
Intervention Type
Biological
Intervention Name(s)
Comparator: placebo (unspecified)
Intervention Description
0.5 mL intramuscular injection in the deltoid muscle at Day 1, Month 2, and Month 6 in the Base Study
Primary Outcome Measure Information:
Title
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
Description
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
Title
Overall Study: Incidence of HPV Type 6/11-related Genital Warts
Description
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
Title
Overall Study: Incidence of HPV Type 6/11/16/18-related External Genital Warts, PIN, Penile, Perianal or Perineal Cancer
Description
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
Title
Overall Study: Incidence of HPV Type 6/11/16/18-related Anal Intraepithelial Neoplasia (AIN) and Anal Cancer
Description
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
Title
Base Study: Number of Participants With Severe Injection Site Adverse Experiences (AEs)
Description
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
Title
Base Study: Number of Participants With Vaccine-Related Serious Adverse Events (SAEs)
Description
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
Title
LTFU (EXT2): Number of Participants With Vaccine-Related SAEs
Description
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
Title
LTFU (EXT2): Number of Participants Who Died
Description
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 Outcome Measure Information:
Title
Base Study: Incidence of HPV 6/11/16/18-related Persistent Infection
Description
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
Title
Base Study: Incidence of HPV 6/11/16/18-related Deoxyribonucleic Acid (DNA) Detection
Description
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
Title
Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 7 Assessed by Competitive Luminex Immunoassay (cLIA)
Description
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
Title
Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 36 Assessed by cLIA
Description
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
Title
Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 72 Assessed by cLIA
Description
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
Title
Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by cLIA
Description
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
Title
Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 7 Assessed by cLIA
Description
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 7
Title
Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 36 Assessed by cLIA
Description
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
Title
Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 72 Assessed by cLIA
Description
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
Title
Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by cLIA
Description
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
Title
Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA)
Description
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
Title
Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by IgG LIA
Description
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
Other Pre-specified Outcome Measures:
Title
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)
Description
Participants with HPV 6/11/16/18-related AIN or anal cancer per 100 person-years of follow-up was assessed.
Time Frame
Base study: through Month 36
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
26 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://www.merck.com/clinicaltrials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
34780705
Citation
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.
Results Reference
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PubMed Identifier
34265048
Citation
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 Feb 18;76(4):778.
Results Reference
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PubMed Identifier
32184277
Citation
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.
Results Reference
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PubMed Identifier
23831322
Citation
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.
Results Reference
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PubMed Identifier
22029979
Citation
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.
Results Reference
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PubMed Identifier
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Citation
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.
Results Reference
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Learn more about this trial
An Investigational Study of Gardasil™ (qHPV Vaccine) in Reducing the Incidence of Anogenital Warts in Young Men (V501-020)
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