| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| E.1.1.1 | Medical condition in easily understood language |
| Prevention of persistent anogenital HPV infection and disease caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | HLGT |
| E.1.2 | Classification code | 10047438 |
| E.1.2 | Term | Viral infectious disorders |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 | 10021881 - Infections and infestations |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10071146 |
| E.1.2 | Term | Human papilloma virus immunisation |
| E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
| 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 |
1.In a population who are seronegative to the relevant human papilloma virus (HPV) type at Day 1, to demonstrate that administration of a 2-dose regimen of 9-valent human papilloma virus vaccine (9vHPV) vaccine in boys and girls 9 to 14 years of age induces noninferior Competitive Luminex Immunoassay (cLIA) geometric mean titers (GMTs) of antibodies to each of the 9vHPV vaccine types compared with young women 16 to 26 years of age receiving a 3-dose regimen of the same vaccine at Day1, Month 2, and Month 6.
2.In 10-to 15-year old boys and girls who received a single dose of 9vHPV vaccine at least 1 year prior to enrollment, to characterize the
immune response to a second dose of 9vHPV vaccine (as measured by cLIA GMTs of antibodies to each of the 9vHPV vaccine types) at
4 weeks post dose 2 taking into account the time interval between administration of doses 1 and 2.
3.To evaluate the safety of administering the 9vHPV vaccine based on the dosing regimens investigated in this study. |
|
| E.2.2 | Secondary objectives of the trial |
1. Cohorts 1-5*: To estimate seroconversion at 4 weeks post last dose to each of the HPV Types 6, 11,16, 18, 31, 33, 45, 52, and 58 (percent of participants seropositive at 4 weeks post last dose).
2. Cohorts 1-5*: To estimate persistence of seroconversion to each of the HPV Types 6,11, 16, 18, 31, 33, 45, 52, and 58 observed at 4 weeks post last dose through estimation of seropositivity at yearly time intervals relative to time of last dose, through 3 years post last dose.
3. Cohorts 1-5*: To estimate persistence of anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 cLIA GMTs observed at 4 weeks post last dose at yearly time intervals relative to time of last dose, through 3 years post last dose.
*Cohort 1: 9-14 year olds receiving 2 doses 12 months apart; Cohort 2: 9-13 year olds receiving 2 doses 24 months apart; Cohort 3: 9-12 year olds receiving 2 doses 36 months apart; Cohort 4: 9-10 year olds receiving 2 doses 60 months apart; and Cohort 5: 16-26 year old women receiving 3 doses. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Is healthy individual who meets all inclusion criteria and none of the exclusion defined in this section.
2. Is male or female, from 10 years to 15 years of age inclusive, who received 1 dose of 9vHPV vaccine at least 1 year prior to enrollment and did not receive Dose 2 of any HPV vaccine (Cohort 0).
3. Is male or female, from 9 years to 14 years of age inclusive, on the day of enrollment (Cohorts 1 to 4).
4. Is female, from 16 years to 26 years inclusive, on the day of enrollment (Cohort 5).
5. (Participants 9 to 15 years of age only) Has not yet had coitarche and does not plan on becoming sexually active during the vaccination period.
6. (Female participants 16 to 26 years of age only) Has never had Pap testing (cervical or anal) or has had only normal Pap test results.
7. (Female participants 16 to 26 years of age only) Has a lifetime history of 0 to 4 male and/or female sexual partners at the time of enrollment. Male or female partner is defined as someone with whom the participant has had penile penetrative sexual intercourse or someone who has contacted, either by penetrative (with fingers or other objects) or nonpenetrative means, the participant's genitalia during sexual activity.
8. (Female participants 16 to 26 years of age only, defined as WOCBP) Has not had sex with males or has had sex with males and used effective contraception with no failures since the first day of the participant’s last menstrual period through Day 1. The participant understands and agrees that during the intervention period, she should not have sexual intercourse with males without effective
contraception, and that the use of the rhythm method, withdrawal, and emergency contraception are not acceptable methods per the protocol. Effective contraception is defined as a marketed, approved contraceptive product that the participant has used per the manufacturer’s instructions with every act of sexual intercourse.
9. Participant or participant’s legally acceptable representative understands the study procedures, alternate treatments available, and risks involved with the study and voluntarily agrees to participate by providing documented informed consent. As appropriate based on local guidelines, the participant will also provide documented informed assent for the study. The participant or the participant’s legally acceptable representative may also provide assent/consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research.
10. Agrees to provide study personnel with a primary telephone number as well as an alternate form of contact, if available, for follow-up purposes.
11. Participant or participant’s legally acceptable representative can read, understand, and complete the eVRC. |
|
| E.4 | Principal exclusion criteria |
1. 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.
2. Has a history of severe allergic reaction (eg, swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that required medical intervention.
3. Is allergic to any vaccine component, including aluminum, yeast, or BENZONASETM (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.
4. Has known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections.
5. 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.
6. Has a history of splenectomy.
7. 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.
8. Has a history of a positive test for HPV.
9. (Female participants 16 to 26 years of age only) Has a history of an abnormal cervical biopsy result (showing cervical intraepithelial neoplasia or worse).
10. (Female participants 16 to 26 years of age only) Has a history of HPV-related external genital lesions (eg, condyloma acuminata, or vulvar intraepithelial neoplasia) or external genital cancer, HPV-related vaginal lesions (eg, condyloma acuminata, or vaginal
intraepithelial neoplasia) or vaginal cancer, or HPV-related anal lesions (eg, condyloma acuminata, or anal intraepithelial neoplasia) or anal cancer.
11. (Female participants only) Is pregnant as determined by a serum pregnancy test or urine pregnancy test that is sensitive to 25 mIU/mL β-hCG.
12. (Female participants only) Is expecting to donate eggs during the intervention period of the study.
13. 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 judgment of investigator.
14. Has received within 12 months prior to enrollment, is receiving, or plans to receive during 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/she 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 corticosteroids 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.
15. Has received within the 3 months prior to the Day 1 vaccination, is receiving, or plans to receive during the study, any immune globulin product (including RhoGAM™ [Ortho- Clinical Diagnostics]) or blood-derived product other than IVIG.
16. 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.
17. Is concurrently enrolled in other clinical studies of investigational agents.
18. Has received more than 1 dose of an HPV vaccine (Cohort 0).
19. Has previously received a marketed or investigational HPV vaccine (Cohorts 1 to 5).
20. Has participated in a clinical study for any HPV vaccine (receiving either active agent or placebo).
21. 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.
22. 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Geometric Mean Titers of Anti-Human Papilloma Virus Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 as Measured by Competitive Luminex Immunoassay
2. Percentage of Participants With at Least 1 Solicited Injection-site Adverse Event
3. Percentage of Participants With at Least 1 Systemic Adverse Event
4. Percentage of Participants With at Least 1 Serious Vaccine-Related Adverse Event |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. 4 weeks postdose 2 (up to ~Month 60)
2. Up to 5 days post vaccination
3. Up to 15 days post vaccination
4. Up to 12 months post last vaccination |
|
| E.5.2 | Secondary end point(s) |
1. Percentage of Participants (Cohorts 1 to 5) Who Are Seropositive for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
2. Geometric Mean Titers ( Cohorts 1 to 5) of Anti HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
3. Percentage of Participants (Cohorts 1 to 5) Who Are Seropositive for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
4. Geometric Mean Titers ( Cohorts 1 to 5) of Anti HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
5. Percentage of Participants (Cohorts 1 to 5) Who Are Seropositive for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
6. Geometric Mean Titers ( Cohorts 1 to 5) of Anti HPV Types 6, 11, 16, 18, 31, 33, 45, 52 , and 58
7. Percentage of Participants (Cohorts 1 to 5) Who Are Seropositive for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 4 weeks post last vaccination
2. 12 months post last vaccination
3. 12 months post last vaccination
4. 24 months post last vaccination
5. 24 months post last vaccination
6. 36 months post last vaccination
7. 36 months post last vaccination |
|
| 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 | No |
| 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 |
|
| 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 | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 5 |
| 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 |
| Colombia |
| Mexico |
| South Africa |
| Taiwan |
| United States |
| Poland |
|
| 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
|
| 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. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 8 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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