This study is testing the immunotherapeutic agent, PDS0101, in adults living with HIV who are also infected with human papillomavirus (HPV) type 16. The purpose of the study is to learn whether PDS0101 is safe and whether it can help the body's immune system respond to HPV 16. Researchers will enroll 27 adults between the ages of 25 and 65 who have been receiving antiretroviral therapy (ART) for at least 12 months, have a cluster of differentiation 4 (CD4) cell count of at least 200 cells/mm³, and have an HIV viral load below 200 copies/mL. All participants must have HPV 16 detected in the cervix, vagina, or anus. Some participants will have high-grade squamous intraepithelial lesions (HSIL), a condition that can lead to cancer. At least 10 participants will have cervical HSIL, and at least 10 will have anal HSIL. Participants with both cervical and anal HSIL will count in both groups. Others may have HPV 16 without HSIL.
This is a single-arm, open-label trial, which means that all participants will receive the same treatment, and both the investigators and the participants will know what the treatment is. Each participant will receive three doses of the PDS0101 vaccine. Participants who receive at least one dose will be included in the study's main safety analysis. If a participant does not receive all three doses and does not experience a serious side effect related to the vaccine (defined as a Grade 3 or higher toxicity), that participant may be replaced to make sure that 27 participants either complete the full vaccination schedule or experience a primary safety event. Participants who do have a qualifying safety event will not be replaced. Even if someone stops the study early, their data will still be included in the final analysis.
The main goals of this study are to evaluate the safety of PDS0101 and to measure the immune response it produces. The safety evaluation includes monitoring for serious or unexpected side effects, especially those that are Grade 3 or higher in severity. The immune response will be assessed by looking at how the body's T cells respond to HPV 16 after PDS0101 administration. The total time a participant is involved in the study includes the PDS0101 administration period and several follow-up visits, which may take place over the course of several months. This research may help inform future strategies for preventing or treating HPV-related disease in people living with HIV.
HPV 16 detected on anal swab, cervical swab or vaginal swab ≤90 days of registration. (Note: HPV 16 detected on this swab can be from the screening evaluation or through standard of care assessments. The HPV 16 assay must be FDA-cleared and report HPV 16 results separately. The assay must be performed in a CLIA-certified laboratory.)
Cervical HSIL cohort: CIN III/carcinoma in situ (CIS), CIN II/III, or CIN II with positive p16 stain diagnosed on cervical biopsy ≤90 days of registration and detection of cervical or vaginal HPV 16.
Cervical HSIL cohort: HSIL must occupy <50% circumference of the cervical squamocolumnar junction, and adequate colposcopy with visualization of the endocervical HSIL margins. (Note: Participants with cervical HSIL occupying ≥50% of the circumference of cervical squamocolumnar junction and/or inadequate visualization of the endocervical HSIL margins are not eligible for this protocol.)
Anal HSIL cohort: anal intraepithelial neoplasia (AIN) III, AIN II/III, or AIN II with positive p16 stain diagnosed on anal or perianal biopsy ≤90 days of registration and detection of anal HPV 16.
AIDS-defining condition within 6 months prior to study entry.
Receipt of blood products within 6 months of enrollment or are currently taking immune suppressants.
History of HPV-related cancer or suspected cancer of the cervix, anus, vagina, vulva, penis, or oropharynx.
Current diagnosis of cancer or prior invasive cancer > T1 stage (other than non-melanoma skin cancer) that has required active treatment within the past 3 years.
Weill Medical College of Cornell University
Lead sponsor
University of Puerto Rico
Collaborator
Montefiore Medical Center
Collaborator
Albert Einstein College of Medicine
Collaborator
University of California, San Diego
Collaborator
H. Lee Moffitt Cancer Center and Research Institute
Collaborator
National Cancer Institute (NCI)
Collaborator
Emory University
Collaborator
University of Maryland, Baltimore
Collaborator