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

Inclusion Criteria

• Biopsy-proven intra-anal or peri-anal HSIL (anal intraepithelial neoplasia [AIN]2 with a positive p16 stain, PAIN2-3, AIN2-3, or PAIN3/AIN3) within 90 days before study enrollment
• 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 within 90 days before study enrollment
• 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 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 separately
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
• 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; the effects of VGX-3100 on the developing human fetus are unknown; it is not known whether VGX-3100 can cross the placenta or cause harm to the fetus when administered to pregnant women or whether it affects reproductive capacity; for this reason, 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; 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 * 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

Exclusion Criteria

• Treatment or removal of HSIL less than 3 months prior to enrollment
• Participants who received prophylactic HPV vaccines (e.g. Gardasil and Cervarix) or any other investigational agents within the 4 weeks before enrollment, other than investigational antiretroviral agents for HIV and investigational agents for Hepatitis C; if participants wish to receive prophylactic HPV vaccines, they must complete the series at least 4 weeks prior to enrollment
• 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 physiologic adrenal replacement doses 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); 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 contraindicate IM injections or use of blood thinners (e.g. anticoagulants or antiplatelet drugs except aspirin) within 2 weeks
• 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) v5.0
• 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; it is not known whether VGX-3100 is excreted in human milk; because of the unknown potential for serious adverse drug reactions in nursing infants, 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