E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of Human Papillomavirus Infections |
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E.1.1.1 | Medical condition in easily understood language |
Genital Warts and anal cancer/precancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063001 |
E.1.2 | Term | Human papilloma virus infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Base study/first extension
Safety: To demonstrate that a 3-dose regimen of GARDASIL (0, 2, 6 mo), is well tolerated in young men.
Efficacy: To demonstrate that a 3-dose regimen of GARDASIL reduces the incidence of HPV 6-,11-,16-, or 18-related external genital warts, PIN, penile, perianal or perineal cancer in young men who are naïve to the relevant HPV type, compared with placebo.
LTFU:
To estimate the long-term effectiveness of qHPV vaccine with respect to the incidence of: 1. HPV 6/11-related external genital warts in young men during a period of 10 years 2. HPV 6/11/16/18-related external genital lesions, including genital warts, penile, perianal, and PIN or penile, perianal, and perineal cancer in young men during a period of 10 years. 3. HPV 6/11/16/18-related AIN and anal cancer in young MSM during a period of 10 years.
To describe incidence of vaccine/procedure-related serious adverse experiences and incidence of deaths in young men who received qHPV vaccine
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E.2.2 | Secondary objectives of the trial |
Base study/first extension
Efficacy: (1) To demonstrate that GARDASIL - 3-dose regimen, reduces the incidence of persistent HPV 6, 11, 16, or 18 infection in young men who are naïve to the relevant HPV type, compared with placebo (2) To demonstrate that GARDASIL- 3-dose regimen, reduces the incidence of HPV 6, 11, 16, or 18 DNA detection at 1 or more visits, in young men who are naïve to the relevant HPV type, compared with placebo.
Immunogenicity: To evaluate the vaccine-induced serum anti-HPV 6, anti-HPV 11, anti-HPV 16 and anti-HPV 18 responses in young men.
LTFU:
Immunogenicity: To evaluate, using the cLIA assay, anti-HPV 6, 11, 16, and 18 immune responses to a 3-dose regimen of qHPV vaccine, for up to 10 years after enrollment in the base study.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
MSM Substudy Efficacy Objective: To investigate the impact of administration of a 3-dose regimen of GARDASIL™ on the combined incidence of HPV 6-, 11-, 16-, or 18-related Anal Intraepithelial Neoplasia (AIN) or Anal Cancer in Men Having Sex with Men (MSM) who are naïve to the relevant HPV type. |
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E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
1.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
2.Overall Study: Incidence of HPV Type 6/11-related Genital Warts
3.Overall Study: Incidence of HPV Type 6/11/16/18-related External Genital Warts, PIN, Penile, Perianal or Perineal Cancer
4.Overall Study: Incidence of HPV Type 6/11/16/18-related Anal Intraepithelial Neoplasia (AIN) and Anal Cancer
5.Base Study: Number of Participants With Severe Injection Site Adverse Experiences (AEs)
6.Base Study: Number of Participants With Vaccine-Related Serious Adverse Events (SAEs)
7.LTFU (EXT2): Number of Participants With Vaccine-Related SAEs
8.LTFU (EXT2): Number of Participants Who Died
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. and 6: Base study: through Month 36
2. to 4: Up to 10 years after the first dose of qHPV vaccine
5: Base study: through Day 5 after any vaccination
7. and 8: 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
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E.5.2 | Secondary end point(s) |
1.Base Study: Incidence of HPV 6/11/16/18-related Persistent Infection
2.Base Study: Incidence of HPV 6/11/16/18-related Deoxyribonucleic Acid (DNA) Detection
3.Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 7 Assessed by Competitive Luminex Immunoassay (cLIA)
4.Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 36 Assessed by cLIA
5.Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 72 Assessed by cLIA
6.Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by cLIA
7.Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 7 Assessed by cLIA
8.Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 36 Assessed by cLIA
9.Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 72 Assessed by cLIA
10.Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by cLIA
11.Geometric Mean Titers to HPV Types 6, 11, 16, and 18 at Month 120 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA)
12.Percentage of Participants Seropositive for HPV Type 6, 11, 16, and 18 at Month 120 Assessed by IgG LIA
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. and 2.: Base study: through Month 36
3. and 7: Month 7
4. and 8: Month 36
5. and 9: Month 72
6., 10, 11 and 12: Month 120
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Participants were followed in EXT1 for 7 months. In EXT 2 [LTFU (EXT2)], long-term effectiveness, immunogenicity, and safety of qHPV vaccine were followed up to 10 years |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Australia |
Brazil |
Canada |
Costa Rica |
Mexico |
Peru |
Philippines |
South Africa |
Taiwan |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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For purposes of analysis and reporting, the overall trial ends when the Sponsor receives the last assay results (e.g. serum, swab, and biopsy) or subject/patient data from the last study related phone-call or visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |