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.
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
Currently pregnant (confirmed by collecting urine for HCG pregnancy test) or lactating
Sequential
Dose Level 1 ACU-D1 ointment
DrugACU-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.
Dose Level 2 ACU-D1 ointment
DrugLevel 2 will consist of 5% ACU-D1 ointment, used twice daily for 4 weeks.
Dose Level 3 ACU-D1 ointment
DrugLevel 3 will consist of 10% ACU-D1 ointment, used twice daily for 4 weeks.
Vulvar/ Perianal Biopsy
Procedure/Surgery3 vulvar or perianal biopsies are to be performed at the screening as well as at the end of the study (week 4).
Maximum tolerated dose (MTD) of ACU-D1
Subjects will be monitored during the trial for adverse events, tolerability and compliance using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The dose level at which no more than 33% of study participants have a DLT will be considered the maximum tolerated dose.
Ability of ACU-D1 to induce p53 and p21 in HPV lesions
The biopsies collected at the the 1st study visit and at the last study visit (week 4) mark will be examined using immunohistochemistry to determine gene activity and be used for other biomolecular assays
Safety of ACU-D1: Time of maximum observed concentration (tmax)
Pharmacokinetic studies will be performed on 3 participants after the 4th week of 10% ACU-D1 ointment application. As part of the studies, these 3 subjects will be admitted to the Grady satellite of the Atlanta Clinical and Translational Science Institute (ACTSI) where blood and urine samples will be collected in quick succession.
Safety of ACU-D1: Maximum concentration (Cmax)
Pharmacokinetic studies will be performed on 3 participants after the 4th week of 10% ACU-D1 ointment application. As part of the studies, these 3 subjects will be admitted to the Grady satellite of the Atlanta Clinical and Translational Science Institute (ACTSI) where blood and urine samples will be collected in quick succession.
Safety of ACU-D1: Area under the concentration-time curve for the last measurable concentration (AUC0-last)
Pharmacokinetic studies will be performed on 3 participants after the 4th week of 10% ACU-D1 ointment application. As part of the studies, these 3 subjects will be admitted to the Grady satellite of the Atlanta Clinical and Translational Science Institute (ACTSI) where blood and urine samples will be collected in quick succession.
Click on the lead sponsor to view all of their trials.
Emory University
Lead sponsor
Georgia Center for Oncology Research & Education
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
