E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of cervical, vulvar, and vaginal cancers and related precancers, external genital lesions, Pap test abnormalities, and persistent infection caused by Human Papillomavirus (HPV) 6, 11, 16, 18, 31, 33, 45, 52, and 58. |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of diseases caused by Human Papillomavirus (HPV) types 6, 11, 16, 18, 31, 33, 45, 52 and 58. |
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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 | 17.0 |
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 |
Main objective of PN001-00 to 03 (Base):
1.To evaluate the tolerability of the V503 when administered to 16- to 26-year-old women.
2.To evaluate a formulation of V503 for use in the efficacy evaluation in Part B.
3.To demonstrate that administration of V503 will reduce the combined incidence of HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical abnormalities (CIN 2/3), Adenocarcinoma In Situ (AIS), invasive cervical carcinoma, high-grade Vulvar Intraepithelial Neoplasia (VIN 2/3), high-grade Vaginal Intraepithelial Neoplasia (VaIN 2/3), vulvar cancer, or vaginal cancer, compared with GARDASIL™ in subjects who are seronegative at Day 1 and PCR negative Day 1 through Month 7 to the relevant HPV type .
Main objective of Extension study PN001-04 is to assessment Immune Memory in Cohort 1.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of PN001-00 to 03:
1. To demonstrate that administration of V503 will reduce the combined incidence of HPV 31-, 33-, 45-, 52-, and 58-related persistent infection detected in samples from two or more consecutive visits (±1 month visit windows) 6 months or longer compared with GARDASIL™ in 16- to 26-year-old adolescent and young adult women who are seronegative at Day 1 and PCR negative Day 1 through Month 7 to the relevant HPV type.
2. To demonstrate that V503 is immunogenic with respect to HPV types 31, 33, 45, 52, and 58.
3. To demonstrate that V503 induces noninferior immune responses with respect to seroconversion percentages for HPV 6, 11, 16, and 18 compared to GARDASIL™.
Secondary objective of Extension study PN001-04 is to evaluate the tolerability of a fourth dose of 9vHPV vaccine in young women who received a 3-dose regimen of 9vHPV vaccine at 16 to 26 years of age in Cohort 1. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria of PN001-00 to 03 (Base):
1. Subject is female, between the ages of 16 years and 0 days and 26 years and 364 days on the day of randomization.
2. Subject has never had Pap testing or has only had normal Pap test results.
3. The subject has the following lifetime sexual history at the time of enrollment:
a) Subject has had 1 to 4 male and/or female sexual partners; or
b) Subject has had 0 male and/or female sexual partners, is 18 years of age or older, and plans to become sexually active within the first 3-6 months of the study.
4. Since the first day of the subject’s last menstrual period through Day 1, the subject has not had sex with males or has had sex with males and used effective contraception with no failures (an example of a failure is a male condom that ruptures during sexual intercourse).
Inclusion criteria for Extension protocol PN001-04 (Cohort 1):
- Subject was enrolled in Part B of the V503-001 base study , was randomized to the V503 cohort, and was in the Per-Protocol Immunogenicity population for at least one HPV type.
- Since the first day of the subject’s last menstrual period through Month 60, the subject has not had sex with males or has had sex with males and used effective contraception with no failures.
Inclusion criteria for Extension protocol PN001-04 (Cohort 2):
- Subject was enrolled in Part A or Part B of the V503-001 base study between 16 and 26 years of age, was randomized to the GARDASI cohort, and received at least 1 dose of GARDASIL.
- Since the first day of the subject’s last menstrual period through Month 60, the subject has not had sex with males or has had sex with males and used effective contraception with no failures (an example of a failure is a male condom that ruptures during sexual intercourse). |
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E.4 | Principal exclusion criteria |
Exclusion criteria of PN001-00 to 03 (Base):
1. Subject has a history of an abnormal cervical biopsy result (showing cervical intraepithelial neoplasia [CIN] or worse).
2. Subject has a history of a positive test for HPV.
3. Subject has received a marketed HPV vaccine, or has participated in an HPV vaccine clinical trial and has received either active agent or placebo.
4. Subject is pregnant (as determined by a serum pregnancy test or urine pregnancy test that is sensitive to 25 mIU/mL β-hCG).
5. Subject has a history of or clinical evidence at the Day 1 pelvic examination of HPV-related external genital lesions (e.g., condyloma acuminata or vulvar intraepithelial neoplasia [VIN]) or external genital cancer, HPV-related vaginal lesions (e.g., condyloma acuminata or vaginal intraepithelial neoplasia [VaIN]) or vaginal cancer.
Exclusion criteria for Extension protocol PN001-04 (Cohort 1 & Cohort 2):
- Subject has known allergy to any vaccine component, including aluminum, yeast, or BENZONASE™.
- Subject has a history of severe allergic reaction (e.g., swelling of the mouth and throat, difficulty breathing, hypotension or shock) that required medical intervention.
- Subject has thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections.
- Subject is concurrently enrolled in clinical studies of investigational agents.
- Subject is pregnant.
- Subject is currently immunocompromised or has been diagnosed as having a congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune condition.
- Subject has had a splenectomy.
- Subject is receiving or has received in the year prior to enrollment in the base study immunosuppressive therapies like radiation therapy, any chemotherapy, monocolonal antibody therapies (including rituximab), intravenous gamma globulin (IVIG) (for a compleze list see exclusion criteria 8 on page 18).
- Subject has received any immune globulin product or blood-derived product within the 3 months prior to the Month 60 vaccination, or (for Cohort 1 only) plans to receive any such product during Month 60 through Month 61 of the study.
- Subject has received non-replicating (inactivated) vaccines within 14 days prior to the Month 60 vaccination or has received replicating (live) vaccines within 21 days prior to the Month 60 vaccination.
- Subject has received an HPV vaccine outside of the context of the V503-001 study.
- Subject has had a fever (defined as an oral temperature of ≥37.8°C) within the 24-hour period prior to the Month 60 vaccination.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint of PN001-00 to 03 (Base):
The primary efficacy endpoint is the combined incidence of HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical abnormalities (CIN 2/3), Adenocarcinoma In Situ (AIS), invasive cervical carcinoma, high-grade Vulvar Intraepithelial Neoplasia (VIN 2/3), high-grade Vaginal Intraepithelial Neoplasia (VaIN 2/3), vulvar cancer, and vaginal cancer.
Endpoint of Extension study PN001-04:
There are no formal hypotheses for this study. Immunogenicity and safety summaries
will be provided for estimation only. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PN001-00 to 03 (Base):
The primary efficacy analysis will be performed after the median follow-up of Part B subjects is approximately 24 months after initial vaccination.
PN001-04 (Extension):
Not applicable |
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E.5.2 | Secondary end point(s) |
In PN001-00 to 03 (Base) after median follow up of Part B.
For PN001-04 (Extension) this is not applicable. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
In PN001-00 to 03 (Base) when subjects are approximately 24 months after initial vaccination.
For PN001-04 (Extension) this is not applicable. |
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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 | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Canada |
Chile |
Colombia |
Hong Kong |
Japan |
Korea, Republic of |
Mexico |
New Zealand |
Peru |
Taiwan |
Thailand |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |