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) Types 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 cervical cancer - prevention of genital warts |
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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 | 20.1 |
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 | 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 |
To evaluate the anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 responses generated following administration of a 3-dose regimen of 9-valent HPV L1 VLP vaccine up to 10 years post-dose 3. |
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E.2.2 | Secondary objectives of the trial |
(1)To estimate the long-term effectiveness of 9-valent HPV L1 VLP vaccine, when administered to 9- to 15-year-old girls /boys, with respect to the combined incidence of persistent HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 infection for a duration of 6 months (within ± 1 month windows) or longer and HPV 6, 11, 16,18, 31, 33, 45, 52, and 58-related Cervical Intraepithelial Neoplasia (CIN),Adenocarcinoma In Situ (AIS), Vulvar Intraepithelial Neoplasia (VIN), Vaginal
Intraepithelial Neoplasia (VaIN), genital warts, and cervical/vaginal/vulvar cancer for girls AND Penile Intraepithelial Neoplasia (PIN), genital warts, and penile/perineal/perianal cancer for boys.
(2):To describe the incidence of serious adverse experiences (deemed to be vaccine-related or procedure-related) in subjects who received 9-valent HPV L1 VLP
vaccine at 9 to 15 years of age. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject was enrolled in Protocol 002 between 9 and 15 years of age and received 3 doses of 9-valent HPV L1 VLP vaccine. |
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E.4 | Principal exclusion criteria |
Subjects who are concurrently enrolled in clinical studies that would involve or interfere with the collection of genital specimens. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Endpoints are gender specific.
--Female Endpoints:
LVPP and EEC swabs will be tested for detection of HPV 6, 11, 16, 18, 31, 33, 35, 39,45, 51, 52, 56, 58, and 59 by PCR assay. PCR analysis of the swabs will be used to
determine persistent HPV infection endpoints.
A thorough external genital wart/lesion inspection will be performed at routine visit intervals. External genital warts/lesions will be biopsied.
Management of subjects 16 to 20 years of age with abnormal Pap test should be consistent with local standards of care and may include, at the investigator’s discretion, observation or colposcopy using a protocol-mandated triage algorithm as outlined below.
Subjects ≥ 21 years of age with abnormal Pap test will be referred to colposcopy using a protocol-mandated triage algorithm. The colposcopist will obtain cervical biopsies of areas of the most severe abnormalities, may decide to take additional biopsies of areas with less severe abnormalities, and may choose to perform an endocervical curettage (ECC) if no cervical dysplasia is observed. A subject may need subsequent cervical
definitive therapy per the protocol-mandated cervical definitive therapy guidelines.
Vaginal lesions will be biopsied if they are observed during a Pap test, colposcopy, or at any other time. In addition, subjects with histologically confirmed HPV-related external genital warts (e.g., condyloma acuminata, VIN, cancer) or vaginal warts (e.g., condyloma acuminata, VaIN, cancer) will be referred to colposcopy if the biopsies were not obtained
during a colposcopy.
Tissue obtained from biopsy and cervical definitive therapy procedures will be analyzed
by MRL HPV Thinsection PCR assay (detection of HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) and by a consensus diagnosis from the HPV Vaccine Program Pathology Panel to determine clinical disease efficacy endpoints.
Male Endpoints:
Penile and glans penis swabs, scrotal swabs, and perineal/perianal swabs will be tested for detection of HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 by PCR assay. PCR analysis of the swabs will be used to determine persistent HPV infection endpoints.
A thorough external genital wart/lesion inspection will be performed at routine visit intervals. External genital warts/lesions will be biopsied.
Tissue obtained from biopsy procedures will be analyzed by MRL HPV Thinsection PCR assay (detection of HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) and by a consensus diagnosis from the HPV Vaccine Program Pathology Panel to determine clinical disease efficacy endpoints. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Immunogenicity Analyses: Immunogenicity summaries are planned to occur at three time points, to include followup data through Month 72, Month 96, and at the end of the study at Month 126.In addition, exploratory analyses regarding the kinetics and persistence of the antibody response may be conducted.
Effectiveness: At the first interim analysis (Month 72), the second interim analysis at Month 96 and at the end of the study at Month 126, summaries of the incidence of HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 related persistent infection for a duration of ≥6 months (within ± 1 month windows) and cervical, vulvar, vaginal, perineal, perianal, and penile intraepithelial preinvasive and invasive disease, and external genital lesions will be provided, separately for males and females. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 |
Immunogenicity - kinetics and persistence of the antibody response - effectiveness by gender and age group. |
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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 | 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.8.3 |
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 | 10 |
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 |
Colombia |
Peru |
South Africa |
Taiwan |
United States |
Austria |
Belgium |
Finland |
Poland |
Spain |
Sweden |
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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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Interim analyses will be conducted at Month 72 and Month 96 to assess the feasibility of continuing through 10 years of follow-up. The decision to continue with the effectiveness
component of the study will depend on the ability to collect sufficient effectiveness data through Months 72 and 96 and as anticipated through the remainder of the study. |
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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 | 10 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 10 |