E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Oral persistent infection caused by any of the human papillomavirus types 16, 18, 31, 33, 45, 52, and 58 |
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E.1.1.1 | Medical condition in easily understood language |
Oral Persistent Infection |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006524 |
E.1.2 | Term | Buccal cavity papilloma |
E.1.2 | System Organ Class | 100000004864 |
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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 |
- To demonstrate that a 3-dose regimen of the 9-valent human papillomavirus vaccine (9vHPV) vaccine will reduce the incidence of human papillomavirus (HPV)16/18/31/33/45/52/58-related oral persistent infection 6 months (± 1-month window) or longer compared with placebo in males 20 to 45 years of age |
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E.2.2 | Secondary objectives of the trial |
- To demonstrate that a 3-dose regimen of the 9-valent human papillomavirus vaccine (9vHPV) vaccine will reduce the incidence of human papillomavirus (HPV) 6/11-related oral persistent infection 6 months (± 1-month window) or longer compared with placebo in males 20 to 45 years of age. - To summarize antibody responses (Geometric Mean Titer [GMT] and seroconversion percentages) to each of human papillomavirus (HPV) 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 7 - To evaluate the safety and tolerability of the 9-valent human papillomavirus vaccine (9vHPV) vaccine when administered to males 20 to 45 years of age
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Is healthy and is judged to be in good physical health based on medical history and physical examination 2.Is male, from 20 years to 45 years of age inclusive, at the time of signing the informed consent 3.Provides written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research. 4.Agrees to provide study personnel with a primary telephone number as well as an alternate means of contact, if available (such as an alternate telephone number or email) for follow-up purposes 5.Can read, understand, and complete the eVRC 6.Has had at least 1 lifetime sexual partner |
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E.4 | Principal exclusion criteria |
1.Has a history of HPV-related anal lesion (anal intraepithelial neoplasia or anal cancer) or HPV-related head and neck cancer 2.Has a history of or clinical evidence at the Day 1 external genital examination of HPV-related external lesion (condyloma acuminata, penile intraepithelial neoplasia or penile cancer) 3.Has clinical evidence at the Day 1 external genital examination of gross genital lesion suggesting sexually transmitted disease 4.Has a fever (defined as oral temperature ≥100.0°F or ≥37.8°C) within the 24-hour period prior to the Day 1 visit* 5.Has a history of severe allergic reaction (eg, swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that required medical intervention 6.Is allergic to any vaccine component, including aluminum, yeast, or BENZONASE™ (nuclease, Nycomed [used to remove residual nucleic acids from this and other vaccines]). For this exclusion criterion, an allergy to vaccine components is defined as an allergic reaction that met the criteria for severe AEs or SAEs 7.Has known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections 8.Is currently immunocompromised or has been diagnosed as having congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition 9.Has a history of splenectomy 10.Has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate by judgement of investigator 11.Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence at the discretion of the investigator. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems because of alcohol use 12.Has received within 12 months prior to enrollment, is receiving, or plans to receive during Day 1 through Month 7 of the study, the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (AravaTM), TNF-α antagonists, monoclonal antibody therapies (including rituximab [Rituxan™]), IVIG, antilymphocyte sera, or other therapy known to interfere with the immune response. Regarding systemic corticosteroids, a participant will be excluded if he is currently receiving steroid therapy, has recently (defined as within 2 weeks of Day 1 vaccination) received such therapy, or has received 2 or more courses of high-dose corticosteroids (≥20 mg/day of prednisone [or equivalent] orally or parenterally) lasting at least 1 week in duration in the year prior to Day 1 vaccination. Participants using inhaled, nasal, or topical steroids are considered eligible for the study. 13.Has received within the 3 months prior to the Day 1 vaccination, is receiving, or plans to receive during Day 1 through Month 7 of the study, any immune globulin product (including RhoGAM™ [Ortho-Clinical Diagnostics]) or blood-derived product other than IVIG 14.Has received inactivated or recombinant vaccines within 14 days prior to Day 1 vaccination or receipt of live vaccines within 21 days prior to Day 1 vaccination* 15.Is concurrently enrolled in other clinical studies of investigational agents 16.Has previously received a marketed HPV vaccine, or has participated in a clinical trial for any HPV vaccine (receiving either active agent or placebo) 17.Has engaged in sexual activity 48 hours prior to Day 1 (this may result in the detection of viral DNA that has been deposited in the oral cavity and is not the result of ongoing infection) * Sexual activity is defined as: •Penile penetrative vaginal intercourse with female partner •Penile penetrative or receptive anal intercourse with male or female partner •Oral sex involving any contact between participant's mouth with a female partner's vagina, genital or anal area; or male partner's penis, genital or anal area. This also includes any contact between participant's partner mouth with participant's penis, genital or anal area. 18.Is unlikely to adhere to the study procedures, keep appointments, or is planning to permanently relocate from the area prior to the completion of the study or to leave for an extended period when study visits would need to be scheduled 19.Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study *: For items denoted with an asterisk, if the exclusion criterion is met, then the Day 1 visit may be rescheduled for a time when the criterion is not met. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1.Incidence of Human Papillomavirus (HPV)16/18/31/33/45/52/58-related 6-month Persistent Oral Infection |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1.Incidence of Human Papillomavirus (HPV) 6/11-related 6-month Persistent Oral Infection 2.Geometric Mean Titers to Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 Antibodies 3.Percentage of Participants who Seroconvert to Human Papillomavirus (HPV) Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 4.Percentage of Participants with at Least 1 Solicited Injection-site Adverse Event (AE) 5.Percentage of Participants with Elevated Temperature (Fever) 6.Percentage of Participants who Report at Least 1 Systemic Adverse Event 7.Percentage of Participants who Experience at Least 1 Serious Adverse Event (SAE) 8.Percentage of Participants who Experience at Least 1 Serious Vaccine-Related Adverse Event |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.Up to Month 42 2.1 month postdose 3 (Month 7) 3.1 month postdose 3 (Month 7) 4.Up to 5 days after any vaccination 5.Up to 5 days after any vaccination 6.Up to 15 days after any vaccination 7.Up to 15 days after any vaccination 8.Up to Month 42 |
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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 |
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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 | Yes |
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 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Colombia |
Israel |
Japan |
Korea, Republic of |
Mexico |
Peru |
Taiwan |
Thailand |
United States |
Belgium |
France |
Germany |
Italy |
Spain |
Czechia |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The overall study ends when the last participant completes the last study-related telephone-call or visit, withdraws from the study, or is lost to follow-up (ie, the participant is unable to be contacted by the investigator).For purposes of analysis and reporting, the overall study ends when the Sponsor receives the last laboratory result or at the time of final contact with the last participant, whichever comes last. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |