Study the safety, toxicity and immunogenicity of naked DNA vaccines inpatients with a HPV-related neoplasia of the vulva.

Phase 1

Conditions: HPV16+ usual type vulvar intraepithelial neoplasia (uVIN)
Therapeutic area: Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

Registration Number: EUCTR2015-005339-42-NL

Lead Sponsor: KI-AV

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Female

Target Recruitment: Not specified

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 affectimmunocompetence
•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)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

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)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: •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). <br>•To study the systemic HPV-specific immune response of sig-HELP-E6SH/E7SH-kdel.<br>;Secondary Objective: •To study the clinical response to vaccination of sig-HELP-E6SH/E7SH-kdel.;Primary end point(s): •Safety: according to the standard procedures. NCI-CTCAE version 4.0 will be used.<br>•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 . <br>;Timepoint(s) of evaluation of this end point: Safety: during the study<br>Systemic immunomonitoring: after first 6 patients and at the end of the study

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Clinical response: by vulvoscopy, drawings on a predesigned vulvoscopy<br>form and monitoring of the lesions by digital photography.;Timepoint(s) of evaluation of this end point: At the end of the study