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NCT Number: NCT05334004

Lopinavir/Ritonavir in PLWH With High-Grade AIN

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.

Recruiting

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Key information

Conditions

High-Grade Anal Intraepithelial Neoplasia

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

UW Digestive Health Center Anoscopy Clinic

Madison, Wisconsin, 53705, United States

Location status: Recruiting

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Lopinavir / Ritonavir

Drug

Human Immunodeficiency Virus (HIV) antiviral, given via suppository

Primary outcomes

  1. 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)

    Time frame: up to 5 weeks

    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.

  2. Rate of Grade 3 or above Toxicities in any Organ System in the Escalation Cohorts

    Time frame: up to 5 weeks

    Grade 3 or above as delineated in Common Terminology Criteria for Adverse Events v 5.0 (CTCAE)

Secondary outcomes

  1. Number of Participants in the Expansion Cohort Who Experience Regression of AIN2/3 Determined by Pathology

    Time frame: week 12, week 40

    Efficacy of intra-anal topical lopinavir/ritonavir administration determined by pathology, based on the regression of AIN2/3 at study weeks 16, 28, and 40. Regression defined as either AIN1 or no AIN lesion detected by High resolution anoscopy (HRA)/biopsy and anal cytology. Down grade of disease from AIN2/3 to AIN1 or normal.

  2. Number of Participants in the Expansion Cohort Determined clear of HPV by PCR test

    Time frame: week 12, week 40

    HPV clearance determined by quantitative polymerase chain reaction (PCR) test.

  3. Number of Tissue Samples with evidence of apoptosis measured by presence of Activated Caspase 3

    Time frame: week 12, week 40

    Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with activated caspase 3 indicate evidence of apoptosis.

  4. Number of Tissue Samples with evidence of autophagy measured by presence of LC3β and p62

    Time frame: week 12, week 40

    Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with LC3β and p62 indicate evidence of autophagy.

  5. Number of Tissue Samples with evidence of cellular proliferation measured by presence of Ki-67

    Time frame: week 12, week 40

    Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with Ki-67 indicate evidence of cellular proliferation.

  6. Number of Tissue Samples with evidence of HPV positivity measured by presence of p16

    Time frame: week 12, week 40

    Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with p16 indicate evidence of HPV positivity.

  7. Number of Tissue Samples with p53 expression

    Time frame: week 12, week 40

    Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue).

Study contacts

Contact information is provided by the study sponsor or research team.

Cancer Connect, MD, FACS

CONTACT

[email protected]

800-622-8922

Sponsors and collaborators

Lead sponsor

University of Wisconsin, Madison

Other

Collaborators

  • Wisconsin Partnership Program

Registry information

Official study title

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)

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
Apr 19, 2022
Registry last updated
May 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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