What is the mechanism of action of this treatment?

The most common treatments for Squamous Intraepithelial Lesion (SIL) often involve stimulating the body's immune response to target and destroy abnormal cells. For instance, VGX-3100 is a DNA plasmid therapeutic vaccine that helps the body build an effective immune response against tumor cells by encoding antigens that trigger an immune attack on HPV-infected cells. Electroporation, on the other hand, enhances the uptake of such vaccines by creating temporary pores in cell membranes, allowing for better drug delivery and stronger immune activation. These mechanisms are crucial for SIL patients as they aim to eradicate precancerous lesions, reduce the risk of progression to invasive cancer, and improve overall treatment efficacy.

What side effects are associated with this type of intervention?

Common treatments for Squamous Intraepithelial Lesion (SIL) that stimulate the immune response and enhance drug uptake, such as therapeutic vaccines and electroporation, have known side effects. Therapeutic vaccines like VGX-3100 can cause injection site reactions, flu-like symptoms, fatigue, and fever. Electroporation may lead to localized pain, swelling, and muscle contractions at the application site. These side effects are generally mild and well-tolerated.

What prior FDA approvals exist?

The FDA has approved several treatments for Squamous Intraepithelial Lesion (SIL) that focus on stimulating the immune response and enhancing drug delivery. One notable example is the use of immune checkpoint inhibitors like pembrolizumab, which enhances the body's immune response against tumor cells. Additionally, treatments such as imiquimod, a topical immune response modifier, have been approved for similar lesions. While electroporation itself is not widely approved, it is being studied in combination with other therapies to improve drug uptake and efficacy.

What other types of research exist?

Promising novel alternatives for treating Squamous Intraepithelial Lesion (SIL) patients include: 1) 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT), which has shown efficacy in treating condylomata acuminata; 2) Intralesional or topical cidofovir, which has been used for recurrent genital warts; 3) Beremagene geperpavec (B-VEC), a gene therapy that delivers a functional version of the COL7A1 gene to skin cells, showing promise in wound healing for epidermolysis bullosa patients. These treatments leverage different mechanisms such as photodynamic action, antiviral properties, and gene therapy to target lesions effectively.

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Cancer Vaccine

VGX-3100 + Electroporation for High-Grade Anal Lesions in HIV

Phase 2

Waitlist Available

Led By Chia-Ching (Jackie) Wang

Research Sponsored by AIDS Malignancy Consortium

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Biopsy-proven intra-anal or per-HSIL at baseline

Must be positive for HPV-16 or -18 on genotyping performed on screening anal swab

Must not have

Condition requiring systemic treatment with corticosteroids or other immunosuppressive medications within 2 weeks of study drug administration

History of anal, penile, vulvar, vaginal, or cervical cancer

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at baseline, 26, 36, 48, 60, and 72 weeks

Awards & highlights

No Placebo-Only Group

Summary

This trial studies a DNA vaccine called VGX-3100 combined with a technique to help it enter cells, aiming to treat HIV-positive patients with severe anal lesions caused by HPV. The vaccine helps the immune system attack harmful cells, and the technique makes it easier for the vaccine to enter the cells. This combination aims to improve treatment effectiveness for these patients. VGX-3100 is being developed as an alternative to surgery for treating precancerous disease while preserving reproductive health.

Who is the study for?

This trial is for HIV-positive individuals with high-grade anal lesions caused by HPV-16 or -18, who have a life expectancy over 5 years and are on effective antiretroviral therapy. They must have certain blood cell counts within normal ranges and be willing to use contraception. People with recent HSIL treatment, allergies to similar drugs, metal implants near the electroporation site, uncontrolled illnesses, or those on certain medications can't join.

What is being tested?

The study tests VGX-3100 (an HPV DNA vaccine) combined with electroporation against high-grade anal lesions in HIV-positive patients. Electroporation helps cells absorb the vaccine better, potentially enhancing immune response to kill tumor cells.

What are the potential side effects?

Possible side effects include reactions at the injection/electroporation site such as pain or swelling, general symptoms like fever or fatigue, and potential immune responses that could affect organ function. The extent of side effects will vary among participants.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My biopsy showed I have high-grade anal lesions.

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I tested positive for HPV-16 or -18 from an anal swab.

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I am on a working antiretroviral therapy for HIV.

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I am fully active and can carry on all pre-disease activities without restriction.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't taken steroids or immunosuppressants in the last 2 weeks.

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I have a history of cancer in the anal, penile, vulvar, vaginal, or cervical area.

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I am currently on treatments that may affect my bone marrow.

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I have metal implants, devices, tattoos, keloids, or skin issues near my treatment area.

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I have many warts that make it hard to see if I have high-grade skin lesions.

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I have a serious heart condition that could be life-threatening.

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I do not have a bleeding or clotting disorder that prevents me from getting IM injections.

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I have fewer than two good spots for an IM injection.

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I am still experiencing side effects from my previous HSIL treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at baseline, 26, 36, 48, 60, and 72 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at baseline, 26, 36, 48, 60, and 72 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and at baseline, 26, 36, 48, 60, and 72 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall response rate at 48 weeks

Secondary study objectives

Complete response rate

Overall response rate at 72 weeks

Safety and tolerability of treatment as assessed by incidence of adverse events

+2 more

Other study objectives

Antibody responses to HPV-16 and HPV-18 E6 and E7

Antibody responses to HPV-16 and HPV-18 E6 and E7 with fourth dose

CD4+ lymphocyte count and complete response

+8 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (VGX-3100, electroporation)Experimental Treatment3 Interventions

Patients 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Electroporation

2015

Completed Phase 1

~10

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Squamous Intraepithelial Lesion (SIL) often involve stimulating the body's immune response to target and destroy abnormal cells. For instance, VGX-3100 is a DNA plasmid therapeutic vaccine that helps the body build an effective immune response against tumor cells by encoding antigens that trigger an immune attack on HPV-infected cells. Electroporation, on the other hand, enhances the uptake of such vaccines by creating temporary pores in cell membranes, allowing for better drug delivery and stronger immune activation. These mechanisms are crucial for SIL patients as they aim to eradicate precancerous lesions, reduce the risk of progression to invasive cancer, and improve overall treatment efficacy.

Interferon-beta and -gamma, but not tumor necrosis factor-alpha, demonstrate immunoregulatory effects on carcinoma cell lines infected with human papillomavirus.