Lopinavir/Ritonavir in PLWH With High-Grade AIN
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Lopinavir / Ritonavir.
- Who it may be relevant to
- Registry conditions: High-Grade Anal Intraepithelial Neoplasia. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official 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)
Overview
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
Interventions
- Drug Lopinavir / Ritonavir
Human Immunodeficiency Virus (HIV) antiviral, given via suppository
Primary outcome measures
- 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]
- Rate of Grade 3 or above Toxicities in any Organ System in the Escalation Cohorts [Time frame: up to 5 weeks]
Secondary outcome measures (7)
- 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
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Prevention
Study locations
United States · 1 center
- UW Digestive Health Center Anoscopy Clinic — Madison
Identifiers
NCT: NCT05334004 · 2023-0052 · SMPH/SURGERY/COLON RECT · Protocol Version 2/24/2026 · 2022-0468 [former] · UW22123