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.
Single group
PDS0101
Biological/VaccinePDS0101 is an HPV 16-targeted immunotherapy administered as two subcutaneous injections of 0.5 mL each (total 1.0 mL). Each dose contains 3.0 mg of Versamune®, a proprietary cationic lipid nanoparticle adjuvant, and 2.7 mg of HPVmix, a blend of HPV16 E6 and E7 proteins. Versamune® enhances antigen uptake and dendritic cell activation, promoting T-cell priming and memory formation. In preclinical studies, subcutaneous administration resulted in low systemic bioavailability (\<6%) and efficient dendritic cell uptake, consistent with a favorable safety profile. PDS0101 has been studied in a completed Phase I trial in HIV-uninfected women with high-risk HPV and cervical intraepithelial neoplasia (CIN) I. Each participant in this study will receive three doses, spaced 21 days apart (± 7 days) unless there has been Grade 3 or greater toxicity at least possibly related to the study agent.
Safety: Number of Grade 3 or greater adverse events (AE) at least possibly related to PDS0101.
Adverse events will be scored according to CTCAE v5.0 grading (Grade 1-Mild, Grade 2-Moderate, Grade 3-Severe, Grade 4-Life-threatening, and Grade 5-Fatal) except for injection site reactions (ISRs) grading, wherein they will be reviewed against 2007 FDA guidance. Skin discoloration is common with PDS0101, therefore skin discoloration (ISRs including erythema or pigment changes) \>10 cm and induration \>10 cm will not count as a primary safety endpoint. However, all of the detailed AEs will be reported as a supporting analysis including all ISRs. For the primary safety analysis, we will include all participants who receive at least one dose of PDS0101. Participants who only receive 1-2 doses who discontinue PDS0101/study participation for reasons other than a primary safety event will be replaced to assure 27 participants who receive all 3 doses or discontinue PDS0101 after 1-2 doses because of a primary safety event; those with primary safety event after 1-2 doses won't be replaced.
Tolerability: Proportion of participants who receive all three doses.
Participants who do not receive the first dose will be excluded from all analyses.
Proportion of participants with an immunotherapeutic agent-induced response.
Immunotherapeutic agent-induced response is defined as a ≥ 3-fold increase over baseline at ≥ 1 of the 4 post-dose administration visits by either interferon gamma (IFN-γ) or granzyme ELISPOT assays, with background subtracted. The proportion with a response by each assay will be reported separately and at each post-study immunotherapeutic agent administration visit.
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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
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