Phase 3
N=203
REVEAL 2 Trial (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)
Cervical Dysplasia · Cervical High Grade Squamous Intraepithelial Lesion · HSIL
Bottom Line
View on ClinicalTrials.gov: NCT03721978 ↗Enrolled (actual)
203
Serious AEs
8.9%
Results posted
Oct 2024
Primary outcome: Primary: Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples — 28.6; 0 percentage of participants — p=0.115
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- VGX-3100 (Biological); Matched Placebo (Biological); CELLECTRA™-5PSP (Device)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- Inovio Pharmaceuticals
- Primary completion
- Aug 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples |
28.6; 0 | 0.115 |
| SECONDARY Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs) |
6; 0; 10; 2; 7; 1 | — |
| SECONDARY Safety Population: Number of Participants With Local and Systemic AEs |
36; 17; 0; 2; 1; 0 | — |
| SECONDARY Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE]) |
20; 4; 3; 0; 0; 0 | — |
| SECONDARY Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE) |
131; 67; 1; 9; 9; 0 | — |
| SECONDARY ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples |
27.6; 8.7 | 0.001 sig |
| SECONDARY Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample |
38.1; 25.0 | — |
| SECONDARY ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample |
34.3; 21.7 | — |
| SECONDARY Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing |
38.1; 0 | — |
| SECONDARY ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing |
38.1; 10.1 | — |
| SECONDARY Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of LSIL or HSIL on Histology Sample |
38.1; 25.0 | — |
| SECONDARY ITT Population: Percentage of Participants With No Evidence of Histologic LSIL or HSIL on Histology Sample |
32.1; 14.5 | — |
| SECONDARY Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing |
28.6; 0 | — |
| SECONDARY ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing |
26.1; 5.8 | — |
| SECONDARY Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma |
76.2; 75.0 | — |
| SECONDARY ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma |
82.1; 76.8 | — |
| SECONDARY Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations |
19.0; 25.0 | — |
| SECONDARY ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations |
22.4; 10.1 | — |
| SECONDARY Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody |
450.0; 1.0; 13.0; 1.0; 4050.0; 1.0 | — |
| SECONDARY mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody |
225.0; 1.0; 1.0; 1.0; 2025.0; 1.0 | — |
| SECONDARY Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36 |
1.67; 4.17; 25.00; 0.00; 15.00; 0.0 | — |
| SECONDARY mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36 |
1.67; 0.00; 10.00; 1.67; 8.33; 0.00 | — |
| SECONDARY Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15 |
0.000; 0.020; 0.035; 0.002; 0.000; 0.027 | — |
| SECONDARY mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15 |
0.000; 0.012; 0.049; 0.000; 0.001; 0.007 | — |
Summary
HPV-303 is a prospective, randomized, double-blind, placebo-controlled 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 human papillomavirus (HPV-16) and/or HPV-18.
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
Data sourced from ClinicalTrials.gov (NCT03721978). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.