| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Papillomavirus Infections |
|
| E.1.1.1 | Medical condition in easily understood language |
| Papillomavirus Infections |
|
| 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 | 27.1 |
| 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.1.3 | 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 administration of the 9-valent human papillomavirus (9vHPV) vaccine induces non-inferior geometric mean titers (GMTs) for serum anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 in females 9 to 19 years of age compared to females 20 to 26 years of age.
To demonstrate that administration of the 9vHPV vaccine induces non-inferior seroconversion percentages to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in females 27 to 45 years of age compared to females 20 to 26 years of age. |
|
| E.2.2 | Secondary objectives of the trial |
| To demonstrate that administration of the 9vHPV vaccine induces non-inferior seroconversion percentages to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in females 9 to 19 years of age compared to females 20 to 26 years of age. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Participant is a Chinese female judged to be in good physical health based on medical history and physical examination
Not a woman of childbearing potential (WOCBP) or if of WOCBP, has not had sex with males or has had sex with males and used effective contraception as defined in Appendix 2 since the first day of participant's last menstrual period through Day 1. And the participant understands and agrees that during the Day 1 through Month 7 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
Has a lifetime history of 0 to 4 male and/or female sexual partners at the time of enrollment. Male partner is defined as someone with whom the participant has penile penetrative sexual intercourse. Female partner is defined as someone who has contacted, either by penetrative (with fingers or other objects) or non-penetrative means, the participant's genitalia during sexual activity
|
|
| E.4 | Principal exclusion criteria |
Known allergy to any vaccine component, including aluminum, yeast, or BENZONASE™ (nuclease, Nycomed™). An allergy to vaccine components is defined as an allergic reaction that met the criteria for serious adverse event
History of severe allergic reaction (e.g. swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that required medical intervention
Known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections
Has a fever (defined as an axillary temperature ≥37.1°C) within 24 hours prior to the Day 1 vaccination
Has any history of abnormal Pap test showing squamous intraepithelial lesion (SIL) or atypical squamous cells - undetermined significance (ASC-US), atypical squamous cells - cannot exclude HSIL (ASC-H), atypical glandular cells, or biopsy showing cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ or cervical cancer
History of external genital wart, vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), vulvar cancer or vaginal cancer
History of a positive test for HPV
Currently immunocompromised or has been diagnosed as having congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune condition
History of splenectomy
Donated blood within 1 week prior to the Day 1 vaccination, or intends to donate during Day 1 through Month 7 of the study
Expecting to donate eggs during Day 1 through Month 7 of the study
Pregnant
Receiving or has received in the year prior to Day 1 vaccination the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (Arava™), tumor necrosis factor (TNF)-α antagonists, monoclonal antibody therapies (including rituximab [Rituxan™]), intravenous gamma globulin (IVIG), antilymphocyte sera, or other therapy known to interfere with the immune response. With regard to systemic corticosteroids, a participant will be excluded if 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 (orally or parenterally) lasting at least 1 week in duration in the year prior to Day 1 vaccination. Participants using inhaled, nasal or topical corticosteroids are considered eligible for the study
Has received immune globulin product (including RhoGAM™ or blood-derived product other than IVIG within 6 months prior to Day 1 vaccination, or plans to receive any such product during Day 1 through Month 7 of the study
Has received a marketed HPV vaccine, or has participated in an HPV vaccine clinical trial and has received either active agent or placebo
Has received inactivated or recombinant vaccines within 14 days prior to Day 1 vaccination or has received live vaccines within 21 days prior to Day 1 vaccination
Concurrently enrolled in clinical studies of interventional agents
a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems as a result of alcohol use
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Stage I: Competitive Luminex Immunoassay (cLIA) GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age and 20 to 26 Years of Age: Month 7
2. Stage I: Percentage of Participants 27 to 45 Years of Age and 20 to 26 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7
3. Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age: Month 12
4. Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month24
5. Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 36
6. Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 48
7. Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 60
8. Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 12
9. Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 24
10. Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 36
11. Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 48
12. Stage II: Percentage of Participants 9 to 19 years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 60
13. Stage II: Immunoglobulin G Luminex Immunoassay (IgG LIA) GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 12
14. Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 24
15. Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 36
16. Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 48
17. Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 60
18. Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 12
19. Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 24
20. Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 36
21. Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 48
22. Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 60
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. 1 month post vaccination 3 (Month 7)
2. 1 month post vaccination 3 (Month 7)
3. Month 12
4. Month 24
5. Month 36
6. Month 48
7. Month 60
8. Month 12
9. Month 24
10. Month 36
11. Month 48
12. Month 60
13. Month 12
14. Month 24
15. Month 36
16. Month 48
17. Month 60
18. Month 12
19. Month 24
20. Month 36
21. Month 48
22. Month 60
|
|
| E.5.2 | Secondary end point(s) |
1. Stage I: Percentage of Participants 9 to 19 Years of Age and 20 to 26 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7
2. Stage I: cLIA GMTs for HPV Tys 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 15 Years of Age and 20 to 26 Years of Age: Month 7
3. Stage I: Percentage of Participants 9 to 15 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7
4. Stage I: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 27 to 45 Years of Age: Month 7
5. Stage I: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age, 20 to 26 Years of Age, and 27 to 45 Years of Age: Month 7
6. Stage I: Percentage of Participants 9 to 19 Years of Age, 20 to 26 Years of Age, and 27 to 45 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7
7. Stage I: Percentage of Participants Who Experience at Least 1 Solicited Injection-site AE
8. Stage I: Percentage of Participants Who Experience at Least 1 Systemic AE
9. Stage I: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)
10. Stage I: Percentage of Participants with Elevated Axillary Temperature (≥37.1 C)
11. Stage II: Percentage of Participant 9 to 19 years of Age Who Experience at Least 1 Serious Adverse Event (SAE): Month 7 to Month 60
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 1 month post vaccination 3 (Month 7)
2. 1 month post vaccination 3 (Month 7)
3. 1 month post vaccination 3 (Month 7)
4. 1 month post vaccination 3 (Month 7)
5. 1 month post vaccination 3 (Month 7)
6. 1 month post vaccination 3 (Month 7)
7. Up to 8 days post any vaccination
8. Up to 30 days post any vaccination
9. Day 1 to Month 7
10. up to 8 days post any vaccination
11. Month 7 to Month 60
|
|
| 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 | No |
| 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 | No |
| 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 | No |
| 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 | 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 | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| 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 | Yes |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
| 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
|
| 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 assay results (eg, serum, swab, and biopsy) or participant data from the last study-related telephone call or visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
