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

Anal Intraepithelial Neoplasia Clinical Trial

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

Status Active, not recruiting

Clinical 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. 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.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. 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:

I. 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.

V. 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:

I. 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.

V. 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. ;

Related Conditions & MeSH terms

• Anal Intraepithelial Neoplasia
• Carcinoma in Situ
• High Grade Squamous Intraepithelial Neoplasia
• HIV Positivity
• Human Papillomavirus-16 Positive
• Human Papillomavirus-18 Positive
• Neoplasms

• NCT number: NCT03603808
• Study type: Interventional
• Source: AIDS Malignancy Consortium
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 21, 2018
• Completion date: September 20, 2029