REVEAL 1 Trial

• Research type

  Research Study

• Full title

  \nA PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 STUDY OF VGX-3100 DELIVERED INTRAMUSCULARLY FOLLOWED BY ELECTROPORATION WITH CELLECTRA™ 5PSP FOR THE TREATMENT OF HPV- 16 AND/OR HPV-18 RELATED HIGH GRADE SQUAMOUS INTRAEPITHELIAL LESION (HSIL) OF THE CERVIX\n

• IRAS ID

  217829

• Contact name

  Margaret Cruickshank

• Contact email

  maggie.cruickshank@nhs.net

• Sponsor organisation

  Inovio Pharmaceuticals, Inc.

• Eudract number

  2016-002761-63

• Duration of Study in the UK

  2 years, 10 months, 30 days

• Research summary

  Research Summary
  Human papillomavirus (HPV) is an infection that can lead to malignant neoplasia. HPV types are classified into high-risk (HR) based on their potential to cause cancer and low-risk (LR) causing generally benign lesions. HPV-16 &HPV-18 are the most significant HR HPV types responsible for most HPV cancers causing 70% of all cervical cancers.\nWhen there is an infection of HPV the ongoing viral replication and shedding is associated with early histologic changes when the female cervix is infected with HPV.\nMost cases of genital HPV infection clear spontaneously but persistent infection with one or more HR HPV genotypes can lead to the development of precancerous, histologic high grade squamous intraepithelial lesions of the cervix (HSIL) including grade 2 & 3 cervical intraepithelial neoplasia (CIN 2/3). Over years cervical HSIL can progress to invasive cancer of the cervix.\nIn the US alone approximately 14 million new genital HPV infections occur annually and half are with a HR HPV. \nThe currently available HPV vaccines; Cervarix™, Gardasil™, and Gardasil™-9 are highly effective in preventing persistent infection and the development of high- grade CIN caused by HPV-16, HPV-18 and other HPV types. However they have no therapeutic effect upon existing HPV infection or existing HPV-related intraepithelial neoplasia. The management of cervical HSIL typically require surgery (i.e. LEEP/LEETZ, laser ablation, or conization); however, surgical excision does not necessarily address the underlying HPV-infection and can adversely impact the reproductive health of women of childbearing age. \nThis is a randomised, double-blind, placebo-controlled phase 3 study to assess the safety and effectiveness of VGX-3100, which is being developed as a non-surgical therapeutic option for precancerous cervical cancer, cervical HSIL, and the underlying, pathogenic HPV infection. VGX-3100 and the CELLECTRA™ 5PSP device is an integrated non- surgical treatment that will target the HPV-16 & HPV-18 antigens. \nApproximately 198 adult women will be randomized in a 2:1 ratio to receive either 6mg (1ml) injection of VGX-3100 or placebo followed by Electroporation (EP) delivered with CELLECTRA™ 5PSP device. The subject will attend 10 clinic visits including administration of 3 study treatments, a physical examination, vital signs, collection of bloods, cervical and vaginal swabs, colonoscopy and cervical biopsy. Subjects will also need to complete Patient-Reported Outcome (PRO) questionnaires (SF-36 and EQ-5D-5L). In addition there will be a follow up of 4 phone calls throughout the study duration of 88 weeks inclusive of follow up.\n

  Summary of Results
  VGX-3100 + EP (Electroporation- microbiology technique in which an electrical field is applied to cells in order to increase the permeability of the cell membrane, allowing chemicals, drugs, electrode arrays or DNA (Deoxyribonucleic Acid - a polymer composed of two polynucleotide chains that coil around each other to form a double helix carrying genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid are nucleic acids.) to be introduced into the cell) showed superior efficacy as compared with placebo + EP in achieving histopathological regression of cervical HSIL (High-Grade Squamous Intraepithelial Lesion )and virologic clearance of HPV (human papilloma virus )-16 and/or HPV‑18 at Week 36 and was safe and well-tolerated by subjects with HPV-16 and/or HPV-18 associated HSIL of cervix.

• REC name

  South Central - Oxford A Research Ethics Committee

• REC reference

  17/SC/0411

• Date of REC Opinion

  4 Apr 2018

• REC opinion

  Further Information Favourable Opinion