Phase I Dose Escalation Study of the Use of ACU-D1, a Topical Proteasome Inhibitor in HPV Associated Vulvar and Perianal Lesions in People With HIV
Emory University
Summary
The goal of this study is to test the maximum tolerated dose of ACU-D1 in HIV-positive people with HPV-associated vulvar and perianal lesions. The main questions it aims to answer are: * The maximum tolerated dose of ACU-D1 * Safety and tolerability of topical ACU-D1 * Whether topical ACU-D1 induces p53 and p53-mediated downstream signaling (including p21 induction) in HPV-related lesions * Whether topical ACU-D1 enhances markers of immunity in HPV-infected HIV-positive individuals Participants will be asked * To apply ACU-D1 on the lesions twice daily for 4 weeks * 3 biopsies will be performed at the screening and 3 at the end of 4 weeks.
Description
From 2016 to 2019, Georgia faced the highest incidence of HIV diagnosis among the fifty states ranging from 40.2 to 26.2 per 100,000 individuals. HIV-infected men and women living in the southern United States experience inadequate treatment services despite bearing the highest burden of new infections as the modern epicenter of the HIV epidemic. There has been considerable research on racial disparities and HIV incidence, but there is a paucity of data on differences in treatment outcomes, particularly those related to comorbidities. HPV and HIV infection are the most significant risk factor…
Eligibility
- Age range
- 21+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Age 21 years and older * HIV-infected * Able to provide informed consent * Biopsy-proven HSIL disease of the vulvar and perianal region with a total disease volume of 3 cm or greater * Combined antiretrovirals (cART) adherence * CD4 count \> 200 cells/ml * Sustained undetectable viral load for ≥ 3 months * If applicable, on reliable birth control such as combined oral contraceptive pills (OCP), bilateral tubal ligation (BTL), a long-acting reversible contraceptive, or Depo-Provera (birth control shot) * Willingness to conform to study requirements * Reliable follow-up an…
Interventions
- DrugDose Level 1 ACU-D1 ointment
ACU-D1 is a topical therapeutic agent that has pentaerythritol tetrakis (3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate) (PTTC) as its major active ingredient. PTTC is a novel proteasome inhibitor that has antiangiogenic and anti-inflammatory activities that reduce pro-inflammatory cytokines. ACU-D1 ointment contains a range of 2.5% to 10% weight by volume of PTTC. Level 1 will consist of 2.5% ACU-D1 ointment, used twice daily for 4 weeks.
- DrugDose Level 2 ACU-D1 ointment
Level 2 will consist of 5% ACU-D1 ointment, used twice daily for 4 weeks.
- DrugDose Level 3 ACU-D1 ointment
Level 3 will consist of 10% ACU-D1 ointment, used twice daily for 4 weeks.
- ProcedureVulvar/ Perianal Biopsy
3 vulvar or perianal biopsies are to be performed at the screening as well as at the end of the study (week 4).
Location
- Grady Memorial HospitalAtlanta, Georgia