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Anal Intraepithelial NeoplasiaPhase 2NCT03603808

VGX-3100 and Electroporation in Treating Patients With HIV-Positive High-Grade Anal Lesions

A Phase 2 study testing Electroporation, HPV DNA Plasmids Therapeutic Vaccine VGX-3100 and Laboratory Biomarker Analysis in people with Anal Intraepithelial Neoplasia and High Grade Squamous Intraepithelial Neoplasia, run by AIDS Malignancy Consortium at 8 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial studies the use of human papillomavirus (HPV) deoxyribonucleic acid (DNA) plasmids therapeutic vaccine VGX-3100 (VGX-3100) and electroporation in treating patients with human immunodeficiency virus (HIV)-positive high-grade anal lesions. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Electroporation, HPV DNA Plasmids Therapeutic Vaccine VGX-3100 and Laboratory Biomarker Analysis
Type of treatment
Vaccines, Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
8 sitesin 2 countries
Study dates
21 Sep 2018to 17 Jun 2025
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Biopsy-proven intra-anal or per-HSIL at baseline (anal intraepithelial neoplasia [AIN]2 with a positive p16 stain, PAIN2-3, AIN2-3, or PAIN3/AIN3)
  • At least one focus of HSIL must be large enough to be monitored for response, i.e., not completely removed after the screening biopsy
  • Must be positive for HPV-16 or -18 on genotyping performed on screening anal swab
  • HIV positive; documentation of HIV-1 infection by means of any one of the following:
  • Documentation of HIV diagnosis in the medical record by a licensed health care provider
  • Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid multispot antibody differentiation assay; NOTE: A ?licensed? assay refers to a U.S. Food and Drug Administration (FDA)-approved assay, which is required for all investigational new drug (IND) studies
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  • Must be documented to be on an effective combination antiretroviral therapy (ART) regimen, generally a 3-drug regimen based on Department of Health and Human Services (DHHS) treatment guidelines by a licensed health care provider; documentation may be a record of an ART prescription in the participant?s medical record, a written prescription in the name of the participant for ART, or pill bottles for ART with a label showing the participant?s name; each component agent of a multi-class combination ART regimen will be counted toward the 3-drug requirement
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Life expectancy of greater than 5 years
  • Within 90 days before enrollment: Leukocytes: >= 3,000/mm^3
  • Within 90 days before enrollment: Absolute neutrophil count: >= 1,500/mm^3
  • Within 90 days before enrollment: Platelets: >= 100,000/mm^3
  • Within 90 days before enrollment: CD4 count >= 350 cells/mm^3
  • Within 90 days before enrollment: HIV plasma HIV-1 RNA below detected limit obtained by Food and Drug Administration (FDA)-approved assays (limit of detection: 75 copies/mL or less)
  • For females, must have cervical cytology and visual examination of the vulva, vagina, and cervix within 12 months prior to enrollment with confirmation of no evidence of carcinoma; for women who underwent hysterectomy with removal of the cervix, cytology from the vagina within 12 months is required
  • For women of child-bearing potential (WOCBP), they must have a negative serum or urine pregnancy test within 72 hours of receiving the first dose of VGX-3100 and be at least 3 months post-partum; WOCBP and men must agree to use adequate contraception (oral contraceptive pills, intrauterine device, Nexplanon, Depo-Provera, or permanent sterilization, etc., or another acceptable method as determined by the investigator) prior to study entry, for the duration of study participation, and 4 months after completion of VGX-3100 administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • A WOCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Men who could father a child must agree to use at least one form of birth control during or continued abstinence from heterosexual intercourse prior to the study, for the duration of study participation, and 4 months after completion of VGX-3100 administration
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Treatment or removal of HSIL less than 3 months prior to enrollment.
  • Patients who received any other investigational agents within the 4 weeks before enrollment, other than investigational antiretroviral agents for HIV and investigational agents for hepatitis C
  • Participants should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 2 weeks of study drug administration; inhaled steroids and adrenal replacement doses =< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; participants are permitted to use ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if >= 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted; use of anabolic steroids is permitted; topical steroids are permitted as long as they are not directly applied to the area of the skin where electroporation is planned
  • History of anal cancer, penile, vulvar, vaginal, or cervical cancer, or signs of any of these malignancies at baseline; participants with prior carcinoma in situ will not be considered to have prior cancer for eligibility purposes
  • Current systemic chemotherapy or radiation therapy that potentially causes bone marrow suppression that would preclude safe treatment of HSIL
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to VGX-3100
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  • Warts so extensive that they preclude the clinician from determining the extent and location of HSIL
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements or could be negatively affected by the electroporation treatment
  • Presence of unstable or life-threatening cardiac disease (e.g. unstable angina, class 3 or higher congestive heart failure)
  • Presence of acute or chronic bleeding or clotting disorder that would be a contraindication to IM injections (which may include the use blood thinners such as anticoagulants or antiplatelets drugs within two weeks of enrollment). Exception: Over-the-counter aspirin or non-steroidal anti-inflammatory drugs is allowed.
  • Participants who have not recovered from adverse events due to prior anti-HSIL therapy (i.e., have residual toxicity > grade 1), per Common Toxicity Criteria for Adverse Events (CTCAE) v4.0
  • Participants who have any metal implants, implanted medical devices, tattoos, keloids or hypertrophic scars, or active lesions/rashes within 2 cm of all intended potential sites of treatment/electroporation
  • History of seizures, except if participants have been seizure-free for 5 years or more with the use of one or fewer anti-epileptic agents
  • Sustained, manually confirmed, sitting systolic blood pressure > 150 mm Hg or < 90 mm Hg or a diastolic blood pressure > 95 mm Hg at screening or day 0
  • Resting heart rate < 50 beats per minute (bpm) (unless attributable to athletic conditioning) or > 100 bpm at screening or day 0
  • Participants who have less than two acceptable sites available for IM injection considering the deltoid and anterolateral quadriceps muscles
  • Participants who have cardioverter-defibrillator or pacemaker (to prevent a life-threatening arrhythmia) that is located ipsilateral to the deltoid injection site (unless deemed acceptable by a cardiologist)
  • Participants who are breastfeeding a child; investigational product should not be administered to nursing mothers
  • Any illness or condition that in the opinion of the investigator may affect the safety of the participant or the evaluation of any study endpoint

Trial locations and contacts

8 sites in 2 countries.

8 sites in 2 countries

United States7 sites

  • Grady Health System

    Atlanta, Georgia, 30303

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Anal Dysplasia Clinic MidWest

    Chicago, Illinois, 60614

  • Laser Surgery Care

    New York, New York, 10011

  • University of California, San Francisco

    San Francisco, California, 94143

  • Montefiore Medical Center

    The Bronx, New York, 10461

  • Wake Forest Baptist health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

Puerto Rico1 site

  • University of Puerto Rico

    San Juan, 00936-3027

Other trials in Puerto Rico

About this study

Official title: A Phase 2 Evaluation of VGX-3100, a Synthetic DNA Immunotherapy Targeting Human Papillomavirus 16 and 18 E6 and E7 Proteins, for Anal High-Grade Squamous Intraepithelial Lesions (HSIL) in HIV-Positive Individuals

This phase II trial studies the use of human papillomavirus (HPV) deoxyribonucleic acid (DNA) plasmids therapeutic vaccine VGX-3100 (VGX-3100) and electroporation in treating patients with human immunodeficiency virus (HIV)-positive high-grade anal lesions. Vaccines made from DNA may help the body build an effective immune response to kill tumor cells. Electroporation helps pores in your body's cells take in the drug to strengthen your immune system's response. Giving VGX-3100 and electroporation together may work better in treating patients with high-grade anal lesions.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the proportion of participants with HPV-16 and/or HPV-18-positive anal high grade squamous intraepithelial neoplasia (HSIL) that achieve either complete or partial response (which is defined as histopathological regression from HSIL to low grade squamous intraepithelial neoplasia [LSIL] or normal) at 48 weeks after the first dose of VGX-3100 (VGX-3100).

SECONDARY OBJECTIVES:

  1. To determine the safety and tolerability as assessed by Common Terminology Criteria for Adverse Events version 5 (CTCAE v5.0).

II. To determine the proportion of participants with HPV-16 and/or HPV-18-positive anal HSIL that achieve complete response (which is defined as histopathological regression from HSIL to normal) at 48 weeks after the first dose of VGX-3100.

III. To determine the proportion of participants who clear HPV-16 and/or HPV-18 (defined as changing from presence to absence of HPV-16 or 18 by anal histological specimen) at 48 weeks after the first dose of VGX-3100.

IV. To determine proportion of participants who clear HPV-16 and/or HPV-18 (defined as changing from presence to absence of HPV-16 and/or 18 by anal swab) at 48 weeks after the first dose of VGX-3100.

  1. To compare the proportion of participants with HPV-16 and/or HPV-18-positive anal HSIL who achieve either complete or partial response (which is defined as histopathological regression from HSIL to LSIL or normal) versus those who do not at 72 weeks after the first dose of VGX-3100.

TERTIARY OBJECTIVES:

  1. To determine the proportion of non-HPV-16 or HPV-18-positive anal HSIL lesions that achieve either complete or partial response (which is defined as histopathological regression from HSIL to LSIL or normal) at 48 weeks after the first dose of VGX-3100.

II. To determine the T cell response to VGX-3100 as measured by interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot (ELISpot), flow cytometric assessments, and T cell infiltration into anal mucosal tissue.

III. To determine the antibody response to VGX-3100 as measured by enzyme-linked immunosorbent assay (ELISA) against HPV-16 E7 and HPV-18 E7 target antigens.

IV. To determine the association of the addition of a fourth dose of VGX-3100 with T-cell and antibody responses.

  1. To determine the association of VGX-3100 immune response with CD4+ lymphocyte count over time.

VI. To determine the association of VGX-3100 immune response with HIV-1 ribonucleic acid (RNA) over time.

VII. To determine if CD4 + lymphocyte count affects the overall or complete response rate at 48 weeks after the first dose of VGX-3100.

VIII. To assess the effect of tissue PD-L1 (programmed death ligand 1) expression and T-cell infiltration on clinical benefit.

OUTLINE:

Patients receive HPV DNA plasmids therapeutic vaccine VGX-3100 intramuscularly (IM) and then undergo electroporation over 10 seconds for 4 doses in week 0, 4, 12, and 24 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 72 weeks.

Being tested
Electroporation, HPV DNA Plasmids Therapeutic Vaccine VGX-3100, Laboratory Biomarker Analysis
Medical subject headings
Squamous Intraepithelial Lesions, HIV Seropositivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ElectroporationDevice

    Also called electroporation therapy, EPT

    Undergo electroporation

  • HPV DNA Plasmids Therapeutic Vaccine VGX-3100Biological

    Also called VGX-3100

    Given IM

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT03603808
Study groupRoleWhat they receive
Treatment (VGX-3100, electroporation)ExperimentalPatients receive HPV DNA plasmids therapeutic vaccine VGX-3100 IM and then undergo electroporation over 10 seconds for 4 doses in week 0, 4, 12, and 24 in the absence of disease progression or unacceptable toxicity.
Receives: Device: Electroporation; Biological: HPV DNA Plasmids Therapeutic Vaccine VGX-3100; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate at 48 Weeks

    Defined as histopathological regression of human papillomavirus (HPV)-16 and/or 18-positive anal high grade squamous intraepithelial neoplasia (HSIL) to low grade squamous intraepithelial neoplasia (LSIL) [anal intraepithelial neoplasia (AIN)1] or normal.

    Measured: At 48 weeks

Secondary outcomes (5)

  1. Safety and Tolerability of Treatment as Assessed by Incidence of Adverse Events

    Safety and tolerability of treatment as assessed by incidence of adverse events assessed by Common Toxicity Criteria for Adverse Events version 5 (CTCAE v.5). Toxicity data will be presented by type and severity.

    Measured: Up to 72 weeks

  2. Complete Response Rate

    Complete response is defined as histopathological regression to normal. The one-sample test of proportions will be used to compare the proportion of participants with HPV-16 and/or HPV-18 positive anal HSIL who were complete responders at 48 weeks after the first dose versus the proportion of participants with HPV-16 and/or HPV-18 positive anal HSIL who were not complete responders at 48 weeks after the first dose of HPV deoxyribonucleic acid (DNA) plasmids therapeutic vaccine VGX-3100.

    Measured: At 48 weeks

  3. Viral Clearance Histological Specimen

    Viral clearance rate of HPV-16 and/or HPV-18 defined as changing from presence to absence of HPV-16/18 in anal HSIL by anal histological specimen. Proportions and their corresponding confidence intervals will be used to estimate the viral clearance rate of HPV-16 and HPV-18.

    Measured: At 48 weeks

  4. Viral Clearance Anal Swab

    Viral clearance rate of HPV-16 and/or HPV-18 defined as changing from presence to absence of HPV-16/18 in anal HSIL by anal swab.

    Measured: Up to 48 weeks

  5. Overall Response Rate at 72 Weeks

    Overall response rate defined as histopathological regression from HSIL to LSIL or normal.

    Measured: At 72 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2018
  2. Study start21 Sep 2018
  3. Primary completion31 Dec 2024
  4. Study completion17 Jun 2025

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03603808
Sponsor's protocol ID
AMC-103
Other IDs
NCI-2017-01740, AMC-103, AMC-103, UM1CA121947, HPV-202
Status last verified
Jun 2026
First submitted
11 Jul 2018
Last updated
8 Jul 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Electroporation, HPV DNA Plasmids Therapeutic Vaccine VGX-3100 and Laboratory Biomarker Analysis in people with Anal Intraepithelial Neoplasia and High Grade Squamous Intraepithelial Neoplasia, run by AIDS Malignancy Consortium at 8 sites in 2 countries.

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 19 inclusion and 19 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 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Puerto Rico. 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 29 Apr 2026). 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?

Overall Response Rate at 48 Weeks (time frame: At 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03603808.

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 8 Jul 2026.

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