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

NCT03603808 | Completed Phase 2 Results DMC FDA Drug FDA Device

• 4 other identifiers: AMC-103NCI-2017-01740UM1CA121947HPV-202
• Study Type: interventional
• Target: 44
• Locations: 2 countries
• Sites: 8

Brief 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. 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.

Conditions

Human Papillomavirus-16 Positive; Human Papillomavirus-18 Positive; Anal Intraepithelial Neoplasia; High Grade Squamous Intraepithelial Neoplasia; HIV Positivity

Outcome Measures

Primary Outcomes (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.

  At 48 weeks

Secondary Outcomes (5)

• Safety and Tolerability of Treatment as Assessed by Incidence of Adverse Events

  Up to 72 weeks

• Complete Response Rate

  At 48 weeks

• Viral Clearance Histological Specimen

  At 48 weeks

• Viral Clearance Anal Swab

  Up to 48 weeks

• Overall Response Rate at 72 Weeks

  At 72 weeks

Other Outcomes (11)

• Response Rate of Non HPV-positive HSIL vs HPV-positive HSIL

  Up to 48 weeks

• T-cell Responses to HPV-16 and HPV-18 E6 and E7

  At baseline, 26, 36, 48, 60, and 72 weeks

• Antibody Responses to HPV-16 and HPV-18 E6 and E7

  At baseline, 26, 36, 48, 60, and 72 weeks

Study Arms (1)

Treatment (VGX-3100, electroporation)

EXPERIMENTAL

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.

Device: Electroporation; Biological: HPV DNA Plasmids Therapeutic Vaccine VGX-3100; Other: Laboratory Biomarker Analysis

Interventions

Electroporation DEVICE

Undergo electroporation

Also known as: electroporation therapy, EPT

Treatment (VGX-3100, electroporation)

HPV DNA Plasmids Therapeutic Vaccine VGX-3100 BIOLOGICAL

Given IM

Also known as: VGX-3100

Treatment (VGX-3100, electroporation)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (VGX-3100, electroporation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• AIDS Malignancy Consortium: lead
• National Cancer Institute (NCI): collaborator
• The Emmes Company, LLC: collaborator
• Inovio Pharmaceuticals: collaborator

Study Sites (8)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Grady Health System

Atlanta, Georgia, 30303, United States

Location

Anal Dysplasia Clinic MidWest

Chicago, Illinois, 60614, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Laser Surgery Care

New York, New York, 10011, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Wake Forest Baptist health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

University of Puerto Rico

San Juan, 00936-3027, Puerto Rico

Location

MeSH Terms

Conditions

Squamous Intraepithelial Lesions; HIV Seropositivity

Interventions

Electroporation; Electroporation Therapies; VGX-3100

Condition Hierarchy (Ancestors)

Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Electrochemical Techniques; Therapeutics

Results Point of Contact

• Title: Himanshu Joshi, MBBS, MPH, PhD
• Organization: Icahn School of Medicine at Mount Sinai

himanshu.joshi@mountsinai.org

2122599635

Study Officials

• Chia-Ching (Jackie) Wang

  AIDS Malignancy Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2018
• First Posted: July 27, 2018
• Study Start: September 21, 2018
• Primary Completion: December 31, 2024
• Study Completion: June 17, 2025
• Last Updated: April 29, 2026
• Results First Posted: April 29, 2026

Record last verified: 2026-04

Locations

PR (1); US (7)