| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Prevention of Human Papillomavirus Infections | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.0 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10063001 | |
| 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 | Primary Safety Objective:
To demonstrate that a 3-dose regimen of quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP vaccine, when administered at 0, 2, and 6 months, is generally well tolerated in 16- to 23-year-old men.
Primary Efficacy Objective:
To demonstrate that quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP vaccine, when given in a 3-dose regimen, reduces the incidence of HPV 6-, 11-, 16- or 18-related anogenital warts in 16- to 23-year-old men who are naïve to the relevant HPV type, compared with placebo.
MSM Substudy Efficacy Objective:
To investigate the impact of administration of a 3-dose regimen of quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP vaccine on the combined incidence of HPV 6-, 11-, 16-, or 18-related Anal Intraepithelial Neoplasia (AIN) or Anal Cancer in MSM subjects who are naïve to the relevant HPV type.
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| E.2.2 | Secondary objectives of the trial | Secondary Efficacy Objectives: (1) To demonstrate that quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP vaccine, when given in a 3-dose regimen, reduces the incidence of persistent HPV 6, 11, 16, or 18 infection in 16- to 23-year-old men who are naïve to the relevant HPV type, compared with placebo (refer to Section I.F.1. for the definition of persistent infection). (2) To demonstrate that quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP vaccine, when given in a 3-dose regimen, reduces the incidence of HPV 6, 11, 16, or 18 detection at one or more visits, in 16- to 23-year-old men who are naïve to the relevant HPV type, compared with placebo.
Immunogenicity Objective: To evaluate the vaccine-induced serum anti-HPV 6, anti-HPV 11, anti-HPV 16, and anti-HPV 18 responses in 16- to 23-year-old men.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | Candidate subjects must meet ALL of the following:
a. Healthy, males between the ages 16 years and 0 days and 23 years and 364 days.
b. No clinical evidence of gross genital lesion suggesting sexually-transmitted disease, and no clinically present anogenital warts.
c. No temperature ≥100°F or ≥37.8°C (oral) within 24 hours prior to vaccinations (vaccinations can be scheduled at a later date when the temperature falls into normal range).
d. Must agree to refrain from sexual activity (including vaginal and anal penetration and any genital contact) for 2 calendar days prior to any scheduled visit that includes sample collection, to avoid detection of viral DNA which has been deposited in the male genital area during sexual intercourse and is not the result of ongoing infection.
e. Individuals who have experienced sexual debut but have had no more than 5 lifetime sexual partners. For protocol purposes, a female sexual partner is defined as a woman with whom the subject has engaged in vaginal intercourse. For protocol purposes, a male sexual partner is defined as a man with whom the subject engaged in insertive or receptive anal intercourse.
f. Must agree to provide study personnel with a primary telephone number as well as an alternate telephone number for follow-up purposes.
g-1) Additional inclusion criteria for heterosexual male subjects
Subjects must be a heterosexual male, who has had exclusively female sexual partners.
g-2) Additional inclusion criteria for MSM subjects
Subjects must have engaged in either insertive or receptive anal intercourse with another male sexual partner within the past year.
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| E.4 | Principal exclusion criteria | Candidate subjects who manifest ANY of the following exclusion criteria at the time of randomization will NOT be eligible for the study:
a. Individuals concurrently enrolled in clinical studies of investigational agents or studies involving collection of genital specimens.
b. History of known prior vaccination with an HPV vaccine.
c. Receipt of inactivated vaccines within 14 days prior to enrollment or receipt of live virus vaccines within 21 days prior to enrollment.
d. Individuals who have history of anogenital warts, or who have clinically present anogenital warts at Day 1.
e. History of severe allergic reaction (e.g., swelling of the mouth and throat, difficulty breathing, hypotension or shock) that required medical intervention.
f. Individuals allergic to any vaccine component, including aluminum, yeast, or BENZONASE™ (nuclease, Nycomed [used to remove residual nucleic acids from this and other vaccines]).
g. Individuals who have received any immune globulin or blood derived products within the 6 months prior to the first injection, or plan to receive any through Month 7 of the study.
h. Individuals with history of splenectomy, known immune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis), or receiving immunosuppressives (e.g., substances or treatments known to diminish the immune response such as radiation therapy, administration of antimetabolites, antilymphocytic sera, systemic corticosteroids). Individuals who have received periodic treatments with immunosuppressives, defined as at least 3 courses of oral corticosteroids each lasting at least 1 week in duration for the year prior to enrollment, will be excluded. Subjects using topical steroids (i.e., inhaled or nasal) will be eligible for vaccination.
i. Individuals who are immunocompromised or have been diagnosed as having Human Immunodeficiency Virus (HIV) infection.
j. Individuals with known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections.
k. History of recent (within the last 12 months) or ongoing alcohol or drug abuse.
Alcohol and drug abusers are defined as those who drink or use drugs despite recurrent social, interpersonal, and legal problems as results of alcohol or drug use.
l. Any condition which in the opinion of the investigator might interfere with the evaluation of the study objectives.
m. Any plan to permanently relocate from the area prior to the completion of the study or to leave for an extended period of time when study visits would need to be scheduled.
n. Individuals with fewer than one or >5 lifetime sexual partners.
o.Inability to give informed consent/assent.
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| E.5 End points |
| E.5.1 | Primary end point(s) | The primary endpoint is HPV 6-, 11-, 16-, 18-related anogenital warts. This endpoint will occur if there is:
–Pathology Panel consensus diagnosis of anogenital warts; AND
–Detection of HPV 6, 11, 16, or 18 DNA by Thinsection PCR in an adjacent section of the same external anogenital lesion biopsy block.
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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 | Information not present in EudraCT |
| 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 | | Amendment 20 concerns a longterm (up to 10 years) evaluation of vaccine effectiveness in males. | |
| 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.8.3 | 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 | Information not present in EudraCT |
| 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 | |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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 | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| 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 |
