Use of ACU-D1 in HPV Associated Vulvar and Perianal Lesions in People With HIV

NCT06233331 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00006195
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Human Papilloma Virus; Human Immunodeficiency Virus; Anal Intraepithelial Neoplasia; High-Grade Squamous Intraepithelial Lesions

Keywords

HIV; HPV; Anal Intraepithelial Neoplasia

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, week 4

Secondary Outcomes (4)

• Ability of ACU-D1 to induce p53 and p21 in HPV lesions

  Baseline, week 4

• Safety of ACU-D1: Time of maximum observed concentration (tmax)

  Before ointment application (0hr), 0.25 hour, 0.50 hour, 1hour, 1.5 hour, 2 hour, 4, 8 hour and 12 hour

• Safety of ACU-D1: Maximum concentration (Cmax)

  Before ointment application (0hr), 0.25 hour, 0.50 hour, 1hour, 1.5 hour, 2 hour, 4, 8 hour and 12 hour

• Safety of ACU-D1: Area under the concentration-time curve for the last measurable concentration (AUC0-last)

  Before ointment application (0hr), 0.25 hour, 0.50 hour, 1hour, 1.5 hour, 2 hour, 4, 8 hour and 12 hour

Study Arms (3)

Level 1

EXPERIMENTAL

Initial three study participants will be enrolled in Dose Level 1, 2.5% ACU-D1 twice daily for 4 weeks.

Drug: Dose Level 1 ACU-D1 ointment; Procedure: Vulvar/ Perianal Biopsy

Level 2

EXPERIMENTAL

If there are no DLTs to Dose Level 1 then, 3 new study participants will proceed to Dose Level 2 at 5% ACU-D1.

Drug: Dose Level 2 ACU-D1 ointment; Procedure: Vulvar/ Perianal Biopsy

Level 3

EXPERIMENTAL

If there are no DLTs to Dose Level 2 then, 3 new study participants will proceed to Dose Level 3 at 10 % ACU-D1.

Drug: Dose Level 3 ACU-D1 ointment; Procedure: Vulvar/ Perianal Biopsy

Interventions

Dose Level 1 ACU-D1 ointment DRUG

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.

Level 1

Dose Level 2 ACU-D1 ointment DRUG

Level 2 will consist of 5% ACU-D1 ointment, used twice daily for 4 weeks.

Level 2

Dose Level 3 ACU-D1 ointment DRUG

Level 3 will consist of 10% ACU-D1 ointment, used twice daily for 4 weeks.

Level 3

Vulvar/ Perianal Biopsy PROCEDURE

3 vulvar or perianal biopsies are to be performed at the screening as well as at the end of the study (week 4).

Level 1; Level 2; Level 3

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 and contact information
• No risk factors or clinical suspicion for micro-invasive disease and absence of medical condition that interferes with the conduct of the study in the investigator's opinion

You may not qualify if:

• Currently pregnant (confirmed by collecting urine for HCG pregnancy test) or lactating

Sponsors & Collaborators

• Emory University: lead
• Georgia Center for Oncology Research & Education: collaborator

Study Sites (1)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Squamous Intraepithelial Lesions

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms

Study Officials

• Lisa Flowers, MD, MPH

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisa Flowers, MD, MPH

CONTACT

678-596-3554; Lflowe2@emory.edu

Nadine Campbell, MD

CONTACT

404-251-8794; nadine.campbell@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This study utilizes a dose escalation phase across a total of 3 dose escalation levels using a standard 3+3 design. Initial three study participants will be enrolled in Dose Level 1 for 4 weeks. If there are no dose-limiting toxicities (DLTs) then 3 new study participants will proceed to Dose level 2. If these 3 study participants do not demonstrate any DLTs then the last 3 study participants will proceed to Dose level 3 for 4 weeks.

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: January 31, 2024
• Study Start: November 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 6, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After analyses have been completed

Locations

US (1)