Conditions: HPV16 Positive Cervical Intraepithelial Neoplasia (CIN 2/3)
Keywords: high grade cervical dysplasia treatment vaccine therapeutic HPV DNA vaccine gene therapy gene gun pre-cancerous
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 132
Healthy volunteers: no

Brief summary:
This study will test the efficacy and safety of different routes of administration of a DNA vaccine in patients with HPV16+ CIN2/3. Subjects will be enrolled in one of six treatment groups. Subjects enrolled in the first two groups will receive vaccination intradermally with a needle-free delivery device. Subjects enrolled in groups 3 and 4 will receive vaccination intramuscularly. Subjects enrolled in groups 5 and 6 will receive vaccine intralesionally.

Detailed description:
Primary Objectives

* To evaluate the feasibility and toxicity of vaccination in women with CIN2/3 caused by HPV16
* To evaluate the effect of vaccination on histology
* To compare immunogenicity of three different routes of administration: intradermal (ID), intramuscular (IM), intralesional (IL).

Secondary Objectives:

* To evaluate changes in HPV viral load
* To evaluate the cellular immune response to vaccination
* To evaluate the humoral immune response to vaccination
* To evaluate local tissue immune response
* To correlate measures of immune response with clinical response
* To correlate measures of immune response with those observed in the preclinical model

Arms:
arm 1: Subjects will receive pNGVL4a-CRT/E7(detox) via gene gun at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15. arm 2: Subjects will receive pNGVL4a-CRT/E7(detox) intramuscularly at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15. arm 3: Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15. arm 4: Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally and imiquimod applied to the cervix at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.

Interventions: intervention 1: DNA vaccination intervention 2: Gene gun vaccine intervention 3: intramuscular vaccination intervention 4: intra-lesional vaccine administration intervention 5: therapeutic resection of the lesion intervention 6: imiquimod
Intervention descriptions: intervention 1: vaccination with pNGVL4a-CRT/E7(detox) intervention 2: 8 micrograms (group 1) or 16 micrograms (group 2) intervention 3: 1mg (group 3) or 3mg (group 4) of pNGVLra-CRT/E7(detox) administered intramuscularly intervention 4: 1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally intervention 5: at week 15, all residual lesions will be resected intervention 6: imiquimod applied to the cervix by the physician

Protocol document: