E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
In this trial, the efficacy of Gardasil combined with imiquimod in women with usual type Vulvar Intraepithelial Neoplasia is investigated. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047778 |
E.1.2 | Term | Vulvar cancer in situ |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066416 |
E.1.2 | Term | Vulvovaginal human papilloma virus infection |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046859 |
E.1.2 | Term | Vaccination |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062059 |
E.1.2 | Term | Histology abnormal |
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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 |
1.Evaluation of efficacy of the following two treatments for usual type VIN: -Vaccination + imiquimod: Vaccination with Gradasil, followed by local applications of imiquimod 5% cream. -Imiquimod alone: Placebo vaccination (saline) followed by local applications of imiquimod 5% cream. 2.Evaluation of the systemic and local immunological response to both treatments.
3.Evaluation of the effect of treatments on HPV DNA presence in VIN lesions, by comparison of Polymerase Chain Reaction (PCR) HPV-DNA detection in vulvar biopsies taken at 0 and 36 weeks.
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E.2.2 | Secondary objectives of the trial |
-Evaluation of effect of vaccination against HPV types 16, 18, 6 and 11 by measuring the antibody titres (against types 16, 18, 6 and 11) at 0, 8, 16, 24 and 36 weeks. -Evaluation of quality of life as measured by quality of life questionnaire at 0 and 36 weeks.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Histological proven usual type VIN, without invasion -Previous treatment with imiquimod for 12-16 weeks with a partial response to imiquimod treatment defined as a reduction in lesion size of 26%-99% -The patient is willing to use a medically acceptable method of contraception throughout the study -Age 18 and above
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E.4 | Principal exclusion criteria |
- (Micro-)invasive carcinoma - Pregnancy and/or breastfeeding - Past history of vulvar cancer - Differentiated (non HPV-related) VIN - Other treatment of VIN or anogenital warts within 1 month of start trial - Hypersensitivity to any components of the vaccine or cream formulation - History of psoriasis or other inflammatory dermatosis of the vulva - Immunodeficiency (e.g. HIV, systemic corticosteroid use) - Insufficient understanding of the Dutch language - Partial responders who are disease-free at study-entry due to other treatment of VIN
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical response to the treatment in VIN lesions after the end of imiquimod treatment and the last vaccination, measured by 1) reduction in lesion size, 2) histological regression of usual type VIN to ‘normal’ vulvar tissue and 3) relieve of symptoms. Other main study parameters are absence of HPV DNA in the original VIN lesions after treatment, normalization of immunocompetent cell counts and production of cytokines in peripheral blood and by Peripheral Blood Mononuclear Cells (PBMCs). Secondary study parameters include presence of antibody titres against HPV 16,18, 6, and 11 and improvement of quality of life. |
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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 | Yes |
E.6.4 | Safety | No |
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 | 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 |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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The end of the study is defined as the last patient’s last visit (at 36 weeks). |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |