Lopinavir/Ritonavir in PLWH With High-Grade AIN

NCT05334004 | Recruiting Phase 1 DMC FDA Drug

• 5 other identifiers: 2023-0052SMPH/SURGERY/COLON RECTProtocol Version 2/24/20262022-0468 [former]UW22123
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

High-Grade Anal Intraepithelial Neoplasia

Outcome Measures

Primary Outcomes (2)

• 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.

  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)

  up to 5 weeks

Secondary Outcomes (7)

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

  week 12, week 40

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

  week 12, week 40

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

  week 12, week 40

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

  week 12, week 40

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

  week 12, week 40

Study Arms (6)

Cohort 1: Lopinavir/Ritonavir 200mg/50mg (2 cycles)

EXPERIMENTAL

Cohort 1 will receive two 5-day cycles of the low dose of the suppository (Lopinavir/Ritonavir (200mg/50mg)) in Weeks 0 and 2

Drug: Lopinavir / Ritonavir

Cohort 1b: Lopinavir/Ritonavir 200mg/50mg (3 cycles)

EXPERIMENTAL

Cohort 1b will receive three 5-day cycles of the low dose of the suppository (Lopinavir/Ritonavir (200mg/50mg)) in Weeks 0, 2, and 4 if Cohort 2 has one dose-limiting toxicity (DLT).

Drug: Lopinavir / Ritonavir

Cohort 2: Lopinavir/Ritonavir 400mg/100mg (2 cycles)

EXPERIMENTAL

Cohort 2 will receive two 5-day cycles of the higher dose of the suppository (Lopinavir/Ritonavir (400mg/100mg)) in Weeks 0 and 2, if Cohort 1 dose is safe.

Drug: Lopinavir / Ritonavir

Cohort 2b: Lopinavir/Ritonavir 400mg/100mg (3 cycles)

EXPERIMENTAL

Cohort 2b will receive three 5-day cycle of the higher dose of the suppository (Lopinavir/Ritonavir (400mg/100mg)) in Weeks 0, 2 and 4 if Cohort 3 has one DLT.

Drug: Lopinavir / Ritonavir

Cohort 3: Lopinavir/Ritonavir 600mg/150mg (2 cycles)

EXPERIMENTAL

Cohort 3 will receive two 5-day cycles of the highest dose of the suppository (Lopinavir/Ritonavir (600mg/150mg)) in Weeks 0 and 2, if the Cohort 2 dose is safe.

Drug: Lopinavir / Ritonavir

Cohort 4: Lopinavir/Ritonavir 600mg/150mg (3 cycles)

EXPERIMENTAL

Cohort 4 will receive three 5-day cycles of the highest dose of the suppository (Lopinavir/Ritonavir (600mg/150mg)) in Weeks 0, 2, and 4, if the Cohort 3 dose is safe.

Drug: Lopinavir / Ritonavir

Interventions

Lopinavir / Ritonavir DRUG

Human Immunodeficiency Virus (HIV) antiviral, given via suppository

Cohort 1: Lopinavir/Ritonavir 200mg/50mg (2 cycles); Cohort 1b: Lopinavir/Ritonavir 200mg/50mg (3 cycles); Cohort 2: Lopinavir/Ritonavir 400mg/100mg (2 cycles); Cohort 2b: Lopinavir/Ritonavir 400mg/100mg (3 cycles); Cohort 3: Lopinavir/Ritonavir 600mg/150mg (2 cycles); Cohort 4: Lopinavir/Ritonavir 600mg/150mg (3 cycles)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Wisconsin Partnership Program: collaborator

Study Sites (1)

UW Digestive Health Center Anoscopy Clinic

Madison, Wisconsin, 53705, United States

RECRUITING

MeSH Terms

Interventions

Lopinavir

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Evie Carchman, MD, FACS

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Connect, MD, FACS

CONTACT

800-622-8922; clinicaltrials@cancer.wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: modified 3+3 design with increasing concentrations of study drug and thorough assessment of potential toxicities.

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 19, 2022
• Study Start: December 19, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 22, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)