Description:
HPV-301 is a prospective, randomized, double-blind, placebo controlled Phase 3 study to
determine the efficacy, safety, and tolerability of VGX-3100 administered by intramuscular
(IM) injection followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women
with histologically confirmed cervical high grade squamous intraepithelial lesion (HSIL)
(cervical intraepithelial neoplasia grade 2 [CIN2] or grade 3 [CIN3]) associated with human
papillomavirus (HPV) 16 and/or HPV-18.
Title
- Brief Title: REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)
- Official Title: 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-301
- SECONDARY ID:
2016-002761-63
- NCT ID:
NCT03185013
Conditions
- Cervical Dysplasia
- Cervical High Grade Squamous Intraepithelial Lesion
- HSIL
Interventions
Drug | Synonyms | Arms |
---|
VGX-3100 | | VGX-3100 + EP |
Placebo | | Placebo + EP |
Purpose
HPV-301 is a prospective, randomized, double-blind, placebo controlled Phase 3 study to
determine the efficacy, safety, and tolerability of VGX-3100 administered by intramuscular
(IM) injection followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women
with histologically confirmed cervical high grade squamous intraepithelial lesion (HSIL)
(cervical intraepithelial neoplasia grade 2 [CIN2] or grade 3 [CIN3]) associated with human
papillomavirus (HPV) 16 and/or HPV-18.
Trial Arms
Name | Type | Description | Interventions |
---|
VGX-3100 + EP | Experimental | IM injections with VGX-3100 followed by electroporation (EP) using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12. | |
Placebo + EP | Placebo Comparator | IM injections with matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12. | |
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 88 |
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. |
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 LSIL (i.e. slightly abnormal cells on the surface of the cervix) or HSIL (i.e. evidence of cervical intraepithelial neoplasia grade 1 [CIN1], CIN2 or CIN3 on biopsies or excisional treatment) 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 LSIL (i.e. slightly abnormal cells on the surface of the cervix) or HSIL (i.e. evidence of CIN1, CIN2 or CIN3 on biopsies or excisional treatment) on histology and no evidence of HPV-16 and/or HPV-18 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 to 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 at the Week 36 Visit. |
Measure: | Change from Baseline in Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations |
Time Frame: | At baseline, Week 15 and Week 36 |
Safety Issue: | |
Description: | Levels of anti-HPV-16 and anti-HPV-18 antibody concentrations will be measured in serum samples of participants using a standardized assay at baseline, Week 15 and Week 36. |
Measure: | Change from Baseline in Interferon-Gamma Response Magnitude |
Time Frame: | At baseline, Week 15 and Week 36. |
Safety Issue: | |
Description: | Peripheral blood mononuclear cells (PBMCs) will be isolated from whole blood samples collected at baseline, Week 15 and Week 36. Assessment of cellular immune activity will be performed. |
Measure: | Change from Baseline in Flow Cytometry Response Magnitude |
Time Frame: | At baseline, Week 15 |
Safety Issue: | |
Description: | Assessment of cellular immune activity will be performed using flow cytometry. |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Inovio Pharmaceuticals |
Trial Keywords
- Cervical intraepithelial neoplasia (CIN)
- Human papillomavirus (HPV)
- High grade squamous intraepithelial lesion (HSIL)
- CIN 2
- CIN 3
- papillomavirus
Last Updated
July 6, 2021