Lopinavir/Ritonavir in PLWH With High-Grade AIN

University of Wisconsin (UW)

Status and phase: Enrolling; Phase 1

Conditions: High-Grade Anal Intraepithelial Neoplasia

Treatments: Drug: Lopinavir / Ritonavir

Study type: Interventional

Funder types: Other

Identifiers

NCT05334004

2023-0052

Protocol Version 3/21/2025 (Other Identifier)

2022-0468 [former] (Other Identifier)

UW22123 (Other Identifier)

SMPH/SURGERY/COLON RECT (Other Identifier)

Details and patient eligibility

About

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.

Full 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

Enrollment: 21 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• willing to provide informed consent
• greater than or equal to 18 years of age
• Diagnosis of biopsy-confirmed HGAIN
• Human immunodeficiency virus (HIV)-positive with CD4 count greater than 200 cells/mm^3 at screening and virologically suppressed on HIV-1 antiretroviral therapy (ART) within last 12 months
• 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.
• Have received topical therapy for anal dysplasia previously

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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21 participants in 6 patient groups

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

Experimental group

Description:

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

Treatment:

Drug: Lopinavir / Ritonavir

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

Experimental group

Description:

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).

Treatment:

Drug: Lopinavir / Ritonavir

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

Experimental group

Description:

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.

Treatment:

Drug: Lopinavir / Ritonavir

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

Experimental group

Description:

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.

Treatment:

Drug: Lopinavir / Ritonavir

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

Experimental group

Description:

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.

Treatment:

Drug: Lopinavir / Ritonavir

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

Experimental group

Description:

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.

Treatment:

Drug: Lopinavir / Ritonavir