Clinical trial NCT00090285: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Condylomata Acuminata
Keywords: anogenital warts
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2004-08-27
Enrollment: 4065
Sex: MALE
Minimum age (years): 16
Maximum age (years): 26
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).


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

Primary outcomes:
measure: 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
timeFrame: Base study: through Month 36
measure: Overall Study: Incidence of HPV Type 6/11-related Genital Warts
timeFrame: Up to 10 years after the first dose of qHPV vaccine
measure: Overall Study: Incidence of HPV Type 6/11/16/18-related External Genital Warts, PIN, Penile, Perianal or Perineal Cancer
timeFrame: Up to 10 years after the first dose of qHPV vaccine
measure: Overall Study: Incidence of HPV Type 6/11/16/18-related Anal Intraepithelial Neoplasia (AIN) and Anal Cancer
timeFrame: Up to 10 years after the first dose of qHPV vaccine
measure: Base Study: Number of Participants With Severe Injection Site Adverse Experiences (AEs)
timeFrame: Base study: through Day 5 after any vaccination
measure: Base Study: Number of Participants With Vaccine-Related Serious Adverse Events (SAEs)
timeFrame: Base study: through Month 36
measure: LTFU (EXT2): Number of Participants With Vaccine-Related SAEs
timeFrame: 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
measure: LTFU (EXT2): Number of Participants Who Died
timeFrame: 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:
measure: Base Study: Incidence of HPV 6/11/16/18-related Persistent Infection
timeFrame: Base study: through Month 36
measure: Base Study: Incidence of HPV 6/11/16/18-related Deoxyribonucleic Acid (DNA) Detection
timeFrame: Base study: through Month 36
measure: Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 7 Assessed by Competitive Luminex Immunoassay (cLIA)
timeFrame: Month 7
measure: Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 36 Assessed by cLIA
timeFrame: Month 36
measure: Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 72 Assessed by cLIA
timeFrame: Month 72
measure: Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by cLIA
timeFrame: Month 120
measure: Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 7 Assessed by cLIA
timeFrame: Month 7
measure: Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 36 Assessed by cLIA
timeFrame: Month 36
measure: Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 72 Assessed by cLIA
timeFrame: Month 72
measure: Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by cLIA
timeFrame: Month 120
measure: Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA)
timeFrame: Month 120
measure: Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by IgG LIA
timeFrame: Month 120
Other outcomes:
measure: 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)
timeFrame: Base study: through Month 36
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
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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.
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.
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.
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.
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.