Clinical Trials /

REVEAL 2 Trial (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)

NCT03721978

Description:

HPV-303 is a prospective, randomized, double-blind, placebo-controlled phase 3 study of VGX-3100 delivered intramuscularly (IM) followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women with histologically confirmed high-grade squamous intraepithelial lesions (HSIL) (cervical intraepithelial neoplasia grade 2 [CIN2] or grade 3 [CIN3]) of the cervix, associated with HPV-16 and/or HPV-18.

Related Conditions:
  • High Grade Cervical Intraepithelial Neoplasia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: REVEAL 2 Trial (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)
  • Official Title: Reveal 2: A 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

Clinical Trial IDs

  • ORG STUDY ID: HPV-303
  • NCT ID: NCT03721978

Conditions

  • Cervical Dysplasia
  • Cervical High Grade Squamous Intraepithelial Lesion
  • HSIL

Interventions

DrugSynonymsArms
VGX-3100VGX-3100 + EP
PlaceboPlacebo + EP

Purpose

HPV-303 is a prospective, randomized, double-blind, placebo-controlled phase 3 study of VGX-3100 delivered intramuscularly (IM) followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women with histologically confirmed high-grade squamous intraepithelial lesions (HSIL) (cervical intraepithelial neoplasia grade 2 [CIN2] or grade 3 [CIN3]) of the cervix, associated with HPV-16 and/or HPV-18.

Trial Arms

NameTypeDescriptionInterventions
VGX-3100 + EPExperimentalIM injections with VGX-3100 followed by electroporation (EP) using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12.
  • VGX-3100
Placebo + EPPlacebo ComparatorIM injections with matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12.
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Women aged 18 years and above

          -  Confirmed cervical infection with HPV types 16 and/or 18 at screening

          -  Cervical tissue specimen/slides provided to Study Pathology Adjudication Committee for
             diagnosis scheduled to be collected within 10 weeks prior to anticipated date of first
             dose of study drug

          -  Confirmed histologic evidence of cervical HSIL at screening

          -  Must be judged by Investigator to be an appropriate candidate for the
             protocol-specified procedure required at Week 36

          -  With respect to their reproductive capacity must be post-menopausal or surgically
             sterile or willing to use a contraceptive method with failure rate of less than 1% per
             year when used consistently and correctly from screening until Week 36

          -  Normal screening electrocardiogram (ECG)

        Exclusion Criteria:

          -  Microscopic or gross evidence of adenocarcinoma-in-situ (AIS), high grade vulvar,
             vaginal, or anal intraepithelial neoplasia or invasive cancer in any histopathologic
             specimen at screening

          -  Cervical lesion(s) that cannot be fully visualized on colposcopy

          -  History of endocervical curettage (ECC) which showed cervical HSIL indeterminate, or
             insufficient for diagnosis

          -  Treatment for cervical HSIL within 4 weeks prior to screening

          -  Pregnant, breastfeeding or considering becoming pregnant during the study

          -  History of previous therapeutic HPV vaccination

          -  Immunosuppression as a result of underlying illness or treatment

          -  Receipt of any non-study, non-live vaccine within 2 weeks of Day 0

          -  Receipt of any non-study, live vaccine within 4 weeks of Day 0

          -  Current or history of clinically significant, medically unstable disease or condition
             which, in the judgment of the investigator, would jeopardize the safety of the
             participant, interfere with study assessments or endpoint evaluation, or otherwise
             impact the validity of the study results

          -  Presence of acute or chronic bleeding or clotting disorder that would contraindicate
             IM injections, or use of blood thinners within 2 weeks of Day 0

          -  Participation in an interventional study with an investigational compound or device
             within 30 days of signing informed consent

          -  Less than two acceptable sites available for IM injection
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with No Evidence of Cervical HSIL on Histology and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples at Week 36
Time Frame:At Week 36
Safety Issue:
Description:Participants will be evaluated for evidence of cervical HSIL on histology as well as evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing at the Week 36 visit.

Secondary Outcome Measures

Measure:Safety: Number of Participants with Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment and for the Duration of the Study
Time Frame:From baseline to Week 40
Safety Issue:
Description:An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. An SAE is any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.
Measure:Percentage of Participants with No Evidence of Cervical HSIL at Week 36
Time Frame:At Week 36
Safety Issue:
Description:Participants will be evaluated for evidence of cervical HSIL on histology at the Week 36 visit.
Measure:Percentage of Participants with No Evidence of HPV-16 and/or HPV-18 in Cervical Samples at Week 36
Time Frame:At Week 36
Safety Issue:
Description:Participants will be evaluated for evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing at the Week 36 visit.
Measure:Percentage of Participants with No Evidence of Low Grade Squamous Intraepithelial Lesion (LSIL) or HSIL at Week 36
Time Frame:At Week 36
Safety Issue:
Description:Participants will be evaluated for evidence of cervical LSIL and HSIL (i.e. no evidence of cervical intraepithelial neoplasia grade 1 [CIN1], CIN2 or CIN3) on histology at the Week 36 visit.
Measure:Percentage of Participants with No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18 at Week 36
Time Frame:At Week 36
Safety Issue:
Description:Participants will be evaluated for evidence of cervical LSIL and HSIL (i.e. no evidence of CIN1, CIN2 or CIN3) on histology and be evaluated for evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing at the Week 36 visit.
Measure:Percentage of Participants with No Progression of Cervical HSIL to Cervical Carcinoma from Baseline at Week 36
Time Frame:At Week 36
Safety Issue:
Description:Participants will be evaluated for progression of cervical HSIL to cervical carcinoma from baseline on histology at the Week 36 visit.
Measure:Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations at Week 36
Time Frame:At Week 36
Safety Issue:
Description:Participants will be evaluated for HPV-16 and/or HPV-18 status in specimens from non-cervical anatomic locations (oropharynx, vagina and intra-anal) at the Week 36 Visit.
Measure:Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations at Weeks 15 and 36
Time Frame:At Weeks 15 and 36
Safety Issue:
Description:
Measure:Interferon-gamma Response Magnitudes at Baseline, Weeks 15 and 36
Time Frame:At Baseline, Weeks 15 and 36
Safety Issue:
Description:Interferon-gamma response magnitudes will be determined using the ELISpot assay at baseline, Weeks 15 and 36 visits.
Measure:Cellular Immune Response Magnitudes at Baseline and Week 15
Time Frame:At Baseline and Week 15
Safety Issue:
Description:Using flow cytometry cellular immune response magnitudes will be determined at the baseline and Week 15 visits.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Inovio Pharmaceuticals

Trial Keywords

  • Cervical intraepithelial neoplasia (CIN)
  • CIN 2
  • CIN 3
  • Human papillomavirus (HPV)
  • HPV-16
  • HPV-18
  • High Grade Squamous Intraepithelial Lesion (HSIL)
  • papillomavirus

Last Updated