RecruitingInterventionalPhase 1

A Phase I Study of Intra-anally Administered Lopinavir/Ritonavir in People Living With HIV (PLWH) With High-Grade Anal Intraepithelial Neoplasia (AIN 2/3)

NCT ID: NCT05334004Sponsor: University of Wisconsin, MadisonLast updated: 2026-05-15

Summary

This study is being done to assess the safety of lopinavir/ritonavir in patients with PLWH with AIN. 30 participants will be recruited and can expect to be on active study for approximately 3 months and long term follow up for 40 weeks.

Detailed description

This is a Phase I modified 3 + 3 design, in which the maximum tolerated dose (MTD) will be identified. The 3 + 3 dose escalation will consist of 6 dose levels (18 participants; planned escalation described in arms below) in combination with variation in dosing schedules of the drug lopinavir/ritonavir. This design also allows for some possible intermediate doses to be examined if dose-limiting toxicities (DLTs) occur and de-escalation is needed. An expansion cohort of 12 participants will occur at the MTD. Once the MTD is determined, then secondary outcomes will be evaluated. Primary Objective * To evaluate the safety and tolerability of intra-anal administration of lopinavir/ritonavir, administered via suppository with 3 different schedules, in PLWH with high-grade anal intraepithelial neoplasia (HGAIN) (AIN 2/3). Secondary Objectives * To measure the effect of intra-anal topical lopinavir/ritonavir administration * To evaluate clearance of human papillomavirus (HPV) * To elucidate the mechanism of action of protease inhibitors

Arms & interventions

DrugLopinavir / Ritonavir
Human Immunodeficiency Virus (HIV) antiviral, given via suppository

Outcome measures

Primary

Maximum Tolerated Dose (MTD) as determined by the number of participants at each dose level in the escalation cohorts who experienced a dose-limiting toxicity (DLT)
The MTD is the highest explored dose of lopinavir/ritonavir is the dose at which less than 33% of patients experienced a DLT. A DLT is defined as any toxicity at least possibly related to ritonavir/lopinavir with a drug-related Grade greater than or equal to 3.
Time frame: up to 5 weeks
Rate of Grade 3 or above Toxicities in any Organ System in the Escalation Cohorts
Grade 3 or above as delineated in Common Terminology Criteria for Adverse Events v 5.0 (CTCAE)
Time frame: up to 5 weeks

Secondary

Number of Participants in the Expansion Cohort Who Experience Regression of AIN2/3 Determined by Pathology
Time frame: week 12, week 40
Number of Participants in the Expansion Cohort Determined clear of HPV by PCR test
Time frame: week 12, week 40
Number of Tissue Samples with evidence of apoptosis measured by presence of Activated Caspase 3
Time frame: week 12, week 40
Number of Tissue Samples with evidence of autophagy measured by presence of LC3β and p62
Time frame: week 12, week 40
Number of Tissue Samples with evidence of cellular proliferation measured by presence of Ki-67
Time frame: week 12, week 40
Number of Tissue Samples with evidence of HPV positivity measured by presence of p16
Time frame: week 12, week 40
Number of Tissue Samples with p53 expression
Time frame: week 12, week 40

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: * willing to provide informed consent * greater than or equal to 18 years of age * Diagnosis of biopsy-confirmed HGAIN * willing to comply with all study procedures Exclusion Criteria: * Diagnosis of low-grade anal dysplasia (AIN, low-grade squamous intraepithelial lesion (LSIL)) by HRA. * CD4 count less than 200 cells/mm\^3 at the time of consideration for entry into the study * unable to provide informed consent * Pregnant or breastfeeding female * Currently receiving systemic chemotherapy or radiation therapy for another cancer.

Study locations (1)

UW Digestive Health Center Anoscopy Clinic

Madison, Wisconsin, 53705

Recruiting