Vulvar High Grade Squamous Intraepithelial Lesion (HSIL)Phase 2NCT03180684
Evaluation of VGX-3100 and Electroporation Alone or in Combination With Imiquimod for the Treatment of HPV-16 and/or HPV-18 Related Vulvar HSIL (Also Referred as: VIN 2 or VIN 3)
A Phase 2 study testing VGX-3100, Imiquimod 5% Cream and CELLECTRA™ 2000 in people with Vulvar High Grade Squamous Intraepithelial Lesion (HSIL) and Vulvar Dysplasia, run by Inovio Pharmaceuticals at 15 sites in United States.
Trial summary
The purpose of this study is to test the safety and efficacy of an investigational immunotherapy VGX-3100, in combination with a study device, to treat women with vulvar high-grade squamous intraepithelial lesion (HSIL) [vulval intraepithelial neoplasia 2 or 3 (VIN 2 or VIN 3)] associated with human papilloma virus… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Vulvar High Grade Squamous Intraepithelial Lesion (HSIL), Vulvar Dysplasia, Vulvar Intraepithelial Neoplasia (VIN)
- What is being tested?
- VGX-3100, Imiquimod 5% Cream and CELLECTRA™ 2000
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 15 sitesUnited States
- Study dates
- 31 Aug 2017to 18 Dec 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women aged 18 and above;
- Have high grade squamous intraepithelial lesion (HSIL) of the vulva (VIN2 or VIN3) caused by infection with HPV types 16 and/or 18 confirmed at screening visit;
Who cannot join
- Biopsy-proven differentiated VIN;
- Any previous treatment for vulvar HSIL within 4 weeks prior to screening;
- Allergy to imiquimod 5% cream or to an inactive ingredient in imiquimod 5% cream;
- Pregnant, breastfeeding or considering becoming pregnant within 6 months following the last dose of investigational product;
- Immunosuppression as a result of underlying illness or treatment;
- Significant acute or chronic medical illness.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
University of Michigan
Ann Arbor, Michigan, 48109
Augusta University
Augusta, Georgia, 30912
Chattanooga's Program in Women's Oncology
Chattanooga, Tennessee, 37403
Rush University Medical Center
Chicago, Illinois, 60612
Complete HealthCare for Women, Inc.
Columbus, Ohio, 43231
St. Dominic Hospital
Jackson, Mississippi, 39216
Froedtert and The Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-2519
Columbia University Medical Center
New York, New York, 10032
Christiana Care Health Systems
Newark, Delaware, 19713
Rutgers New Jersey
Newark, New Jersey, 07103
University of Pittsburgh Medical Center - Magee Womens Hospital
Pittsburgh, Pennsylvania, 15213
Maine Medical Center
Scarborough, Maine, 04074
Montefiore Medical Center
The Bronx, New York, 10461
Lyndhurst Clinical Research
Winston-Salem, North Carolina, 27103
About this study
Official title: A Phase 2, Randomized, Open Label, Efficacy Study of VGX-3100 Delivered Intramuscularly Followed by Electroporation With CELLECTRA™ 2000 Alone or in Combination With Imiquimod, for the Treatment of HPV-16 and/or HPV-18 Related High Grade Squamous Intraepithelial Lesion (HSIL) of the Vulva
The purpose of this study is to test the safety and efficacy of an investigational immunotherapy VGX-3100, in combination with a study device, to treat women with vulvar high-grade squamous intraepithelial lesion (HSIL) [vulval intraepithelial neoplasia 2 or 3 (VIN 2 or VIN 3)] associated with human papilloma virus (HPV) types 16 and/or 18. VGX-3100 is being assessed as an alternative to surgery with the potential to clear the underlying HPV infection. For more information visit our study website at: www.VINresearchstudy.com
- Conditions
- Vulvar High Grade Squamous Intraepithelial Lesion (HSIL), Vulvar Dysplasia, Vulvar Intraepithelial Neoplasia (VIN), VIN2, VIN3, Pre-cancerous Lesions of the Vulva
- Being tested
- VGX-3100, Imiquimod 5% Cream, CELLECTRA™ 2000
- Keywords
- HPV-16, HPV-18
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VGX-3100Biological
One milliliter (1 mL) VGX-3100 injected IM and delivered by EP using CELLECTRA™ 2000 on Day 0, Week 4, Week 12 and Week 24.
Imiquimod 5% CreamDrug
Participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.
CELLECTRA™ 2000Device
IM injection of VGX-3100 was followed by EP with the CELLECTRA™ 2000 device.
| Study group | Role | What they receive |
|---|---|---|
| VGX-3100 + EP | Experimental | Participants with histologically confirmed vulvar high-grade squamous intraepithelial lesion (HSIL) associated with human papilloma virus (HPV) 16 and/or 18, received four doses of 6 mg VGX-3100 as an intramuscular (IM) injection on Day 0, Week 4, Week 12, and Week 24 followed by electroporation (EP) using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. Receives: Biological: VGX-3100; Device: CELLECTRA™ 2000 |
| VGX-3100 + EP + Imiquimod | Experimental | Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks. Receives: Biological: VGX-3100; Drug: Imiquimod 5% Cream; Device: CELLECTRA™ 2000 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With No Histologic Evidence of Vulvar HSIL and No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples
A treatment responder for the primary endpoint was defined as a participant with no histologic evidence of vulvar HSIL (normal tissue or vulvar low grade squamous intraepithelial lesions (LSIL) [vulval intraepithelial neoplasia 1 (VIN1)] or condyloma) and no evidence of HPV-16 or HPV-18 (i.e., elimination of the specific genotypes [16, 18, or both]) in vulvar tissue at evaluation and who did not receive any non-study related treatment for vulvar HSIL. All lesions were evaluated for histologic evidence of vulvar HSIL or evidence of HPV-16/18 in vulvar tissue.
Measured: Week 48
Secondary outcomes (11)
Percentage of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose
An adverse event (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, or worsening of a pre-existing condition, temporally associated with the use of a product whether or not considered related to the use of the product. A TEAE was defined per protocol as any AE with onset after the administration of study medication through the end of the study (i.e., study discharge).
Measured: 7 days following each dose: Day 0 (Days 0 to 7), Week 4 (Days 22 to 28), Week 12 (Days 78 to 84), Week 24 (Days 162 to 168), and Week 52 (Days 358 to 364)
Percentage of Participants With Adverse Events (AEs)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, or worsening of a pre-existing condition, temporally associated with the use of a product whether or not considered related to the use of the product.
Measured: From baseline up to Week 100
Percentage of Participants With No Histologic Evidence of Vulvar HSIL
Participants with no histologic evidence of vulvar HSIL (normal tissue or vulvar LSIL [VIN1] or condyloma) based on histology (i.e. biopsies or excisional treatment) were considered. All lesions were evaluated for histologic evidence of vulvar HSIL.
Measured: Week 48
Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples
Participants with no evidence of HPV-16 and/or HPV-18 indicated the clearance of the specific HPV genotypes [16, 18, or both]. All lesions were evaluated for evidence of HPV-16/18 in vulvar tissue.
Measured: Week 48
Percentage of Participants With No Histologic Evidence of Vulvar HSIL or No Evidence of HPV-16/18 in Vulvar Tissue
A treatment responder for the endpoint was defined as a participant with no histologic evidence of vulvar HSIL (normal tissue or LSIL [VIN1] or condyloma) based on histology (i.e. biopsies or excisional treatment) or no evidence of HPV-16 or HPV-18 (i.e., elimination of the specific genotypes [16, 18, or both]) in vulvar tissue at evaluation and who did not receive any non-study related treatment for vulvar HSIL. All lesions were evaluated for histologic evidence of vulvar HSIL or evidence of HPV-16/18 in vulvar tissue.
Measured: Week 48
Percentage of Participants With No Evidence of Vulvar HSIL, No Evidence of Vulvar LSIL (VIN1), and No Evidence of Condyloma on Histology
Histologic regression was defined as a participant with no histologic evidence of vulvar HSIL, no evidence of LSIL (VIN1), and no evidence of condyloma. Histologic regression of vulvar HSIL to normal tissue was assessed.
Measured: Week 48
Percentage of Participants With No Progression of Vulvar HSIL to Vulvar Cancer
Non-progression of vulvar HSIL to vulvar cancer was evaluated from baseline to Week 48. Progression was defined as advancement to carcinoma by histology.
Measured: From baseline up to Week 48
Percent Change From Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s)
Lesion(s), defined as areas that stain acetowhite were assessed. Analysis of qualifying lesions was defined as the change in total surface area of only lesions with both baseline and Week 48 measurements. Percent change in the cumulative surface area of the acetowhite vulvar lesion(s) was determined by the quantitative analysis of standardized prebiopsy photographic imaging of qualifying lesion(s) at Week 48 compared to baseline.
Measured: From baseline to Week 48
Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude
Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples. Assessment of cellular immune activity was performed by IFN-γ enzyme-linked immunosorbent spot-forming (ELISpot) assay.
Measured: Baseline; Weeks 15, 27, 48, 74, and 96
Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations
A standardized binding enzyme-linked immunosorbent assay (ELISA) was performed to measure the anti-HPV-16/18 antibody response induced by VGX-3100.
Measured: Weeks 15, 27, 48, 74, and 96
Change From Baseline in Flow Cytometry Response Magnitude
Assessment of cellular immune activity was measured using the application of flow cytometry for the purpose of performing a Lytic Granule Loading Assay. The Lytic Granule Loading Assay examines the following external cellular markers: cluster of differentiation 3 (CD3), CD4, CD8 (T-cell identification), CD137, CD38, and CD69 (T-cell activation markers) as well as PD-1 (exhaustion/activation marker). Here, a change from baseline in CD8+/CD137+ PBMCs expressing Perforin+ was reported.
Measured: Baseline; Week 27
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2017
- Study start31 Aug 2017
- Primary completion23 Jul 2020
- Study completion18 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Vulvar High Grade Squamous Intraepithelial Lesion (HSIL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inovio Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jeffrey Skolnik, MD, Study director, Inovio Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03180684
- Sponsor's protocol ID
- HPV-201
- Status last verified
- Aug 2023
- First submitted
- 6 Jun 2017
- Last updated
- 25 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Open Label, Efficacy Study of VGX-3100 Delivered Intramuscularly Followed by Electroporation With CELLECTRA™ 2000 Alone or in Combination With Imiquimod, for the Treatment of HPV-16 and/or HPV-18 Related High Grade Squamous Intraepithelial Lesion (HSIL) of the Vulva
- ClinicalTrials.gov ID
- NCT03180684
- Acronym / sponsor ID
- HPV-201
- Conditions
- Vulvar High Grade Squamous Intraepithelial Lesion (HSIL), Vulvar Dysplasia, Vulvar Intraepithelial Neoplasia (VIN), VIN2, VIN3, Pre-cancerous Lesions of the Vulva
- Keywords
- HPV-16, HPV-18
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Inovio PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 31 Aug 2017 (actual)
- Primary completion
- 23 Jul 2020 (actual)
- Study completion
- 18 Dec 2020 (actual)
- First posted
- 8 Jun 2017 (actual)
- Results
- Posted 25 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the safety and efficacy of an investigational immunotherapy VGX-3100, in combination with a study device, to treat women with vulvar high-grade squamous intraepithelial lesion (HSIL) [vulval intraepithelial neoplasia 2 or 3 (VIN 2 or VIN 3)] associated with human papilloma virus (HPV) types 16 and/or 18. VGX-3100 is being assessed as an alternative to surgery with the potential to clear the underlying HPV infection. For more information visit our study website at: www.VINresearchstudy.com
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VGX-3100 + EP | Experimental | Biological: VGX-3100, Device: CELLECTRA™ 2000Participants with histologically confirmed vulvar high-grade squamous intraepithelial lesion (HSIL) associated with human papilloma virus (HPV) 16 and/or 18, received four doses of 6 mg VGX-3100 as an intramuscular (IM) injection on Day 0, Week 4, Week 12, and Week 24 followed by electroporation (EP) using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. |
| VGX-3100 + EP + Imiquimod | Experimental | Biological: VGX-3100, Drug: Imiquimod 5% Cream, Device: CELLECTRA™ 2000Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Women aged 18 and above;
- Have high grade squamous intraepithelial lesion (HSIL) of the vulva (VIN2 or VIN3) caused by infection with HPV types 16 and/or 18 confirmed at screening visit;
Key exclusion criteria (6 listed)
- Biopsy-proven differentiated VIN;
- Any previous treatment for vulvar HSIL within 4 weeks prior to screening;
- Allergy to imiquimod 5% cream or to an inactive ingredient in imiquimod 5% cream;
- Pregnant, breastfeeding or considering becoming pregnant within 6 months following the last dose of investigational product;
- Immunosuppression as a result of underlying illness or treatment;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VGX-3100One milliliter (1 mL) VGX-3100 injected IM and delivered by EP using CELLECTRA™ 2000 on Day 0, Week 4, Week 12 and Week 24. | Biological | VGX-3100 + EP, VGX-3100 + EP + Imiquimod |
| Imiquimod 5% CreamParticipants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks. | Drug | VGX-3100 + EP + Imiquimod |
| CELLECTRA™ 2000IM injection of VGX-3100 was followed by EP with the CELLECTRA™ 2000 device. | Device | VGX-3100 + EP, VGX-3100 + EP + Imiquimod |
Primary outcome
Percentage of Participants With No Histologic Evidence of Vulvar HSIL and No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples
Time frame: Week 48
A treatment responder for the primary endpoint was defined as a participant with no histologic evidence of vulvar HSIL (normal tissue or vulvar low grade squamous intraepithelial lesions (LSIL) [vulval intraepithelial neoplasia 1 (VIN1)] or condyloma) and no evidence of HPV-16 or HPV-18 (i.e., elimination of the specific genotypes [16, 18, or both]) in vulvar tissue at evaluation and who did not receive any non-study related treatment for vulvar HSIL. All lesions were evaluated for histologic evidence of vulvar HSIL or evidence of HPV-16/18 in vulvar tissue.
11 secondary outcomes
Percentage of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose
Time frame: 7 days following each dose: Day 0 (Days 0 to 7), Week 4 (Days 22 to 28), Week 12 (Days 78 to 84), Week 24 (Days 162 to 168), and Week 52 (Days 358 to 364)
Percentage of Participants With Adverse Events (AEs)
Time frame: From baseline up to Week 100
Percentage of Participants With No Histologic Evidence of Vulvar HSIL
Time frame: Week 48
Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples
Time frame: Week 48
Percentage of Participants With No Histologic Evidence of Vulvar HSIL or No Evidence of HPV-16/18 in Vulvar Tissue
Time frame: Week 48
Percentage of Participants With No Evidence of Vulvar HSIL, No Evidence of Vulvar LSIL (VIN1), and No Evidence of Condyloma on Histology
Time frame: Week 48
Percentage of Participants With No Progression of Vulvar HSIL to Vulvar Cancer
Time frame: From baseline up to Week 48
Percent Change From Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s)
Time frame: From baseline to Week 48
Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude
Time frame: Baseline; Weeks 15, 27, 48, 74, and 96
Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations
Time frame: Weeks 15, 27, 48, 74, and 96
Change From Baseline in Flow Cytometry Response Magnitude
Time frame: Baseline; Week 27
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Skolnik, MD study director
Inovio Pharmaceuticals
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VGX-3100, Imiquimod 5% Cream and CELLECTRA™ 2000 in people with Vulvar High Grade Squamous Intraepithelial Lesion (HSIL) and Vulvar Dysplasia, run by Inovio Pharmaceuticals at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With No Histologic Evidence of Vulvar HSIL and No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples (time frame: Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2023.