E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HPV16+ usual type vulvar intraepithelial neoplasia (uVIN) |
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E.1.1.1 | Medical condition in easily understood language |
HPV16+ neoplasia of the vulva |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
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 study the safety of two naked DNA vaccines encoding sig-HELP-kdel and shuffled HPV16 E6 or E7 gene products (sig-HELP-E6SH/E7SH-kdel). • To study the systemic HPV-specific immune response of sig-HELP-E6SH/E7SH-kdel.
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E.2.2 | Secondary objectives of the trial |
• To study the clinical response to vaccination of sig-HELP-E6SH/E7SH-kdel. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age above 18 years • Willing and able to undergo the planned study procedures • Written informed consent • Histologically proven visible uVIN lesion (histology ≤3 months prior to enrolment and at least 6 weeks after last treatment) • HPV16-positive VIN lesion (to be determined on archival tumour tissue (≤10 years old); if not available a new biopsy will be required) • No indication of an active infectious disease: HIV, HCV and HBV negative • No history of autoimmune disease or systematic undercurrent disease which might affect immunocompetence • Adequate bone marrow (WBC > 3.0/nL, platelets > 100/nL), renal function (creatinine clearance > 40 mL/min), and liver function (bilirubin < 1.5 x ULN, normal blood coagulation)
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E.4 | Principal exclusion criteria |
• Prior treatment with anti-HPV agents • Participation in a study with another investigational drug within 30 days prior to enrolment in this study • Severe cardiac, respiratory, or metabolic disease • Use of systemic steroids or other immunosuppressive drugs • Use of oral anticoagulant drugs (except ascal) • Severe infections requiring antibiotics • Any treatment for the uVIN lesion within 6 weeks prior to the enrolment (including imiquimod) • Lactation or pregnancy (if applicable) • Not willing to take adequate contraceptive measures (if applicable)
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E.5 End points |
E.5.1 | Primary end point(s) |
• Safety: according to the standard procedures. NCI-CTCAE version 4.0 will be used. • Systemic immunemonitoring: the induction of a systemic HPV16-specific T-cell response will be studied in peripheral blood samples; vaccine-specific T cells will be quantified and characterized using polychromatic flow cytometry and ELISPOT assay .
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety: during the study Systemic immunomonitoring: after first 6 patients and at the end of the study |
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E.5.2 | Secondary end point(s) |
Clinical response: by vulvoscopy, drawings on a predesigned vulvoscopy form and monitoring of the lesions by digital photography. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |