← Back to Search

Protease Inhibitor

Lopinavir/Ritonavir for Anal Intraepithelial Neoplasia

Phase 1
Recruiting
Led By Evie Carchman, MD, FACS
Research Sponsored by University of Wisconsin, Madison
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Greater than or equal to 18 years of age
Diagnosis of biopsy-confirmed HGAIN
Must not have
Participants who need to take drugs that are contraindicated with lopinavir/ritonavir
Unable to provide informed consent
Timeline
Screening 3 weeks
Treatment Varies
Follow Up week 12, week 40
Awards & highlights
All Individual Drugs Already Approved
Approved for 5 Other Conditions
No Placebo-Only Group

Summary

This trial is testing a suppository form of HIV medications lopinavir and ritonavir in patients with HIV who have a precancerous condition in the anal area. The goal is to see if these medications can safely reduce or clear the precancerous cells and HPV infection. Lopinavir and ritonavir are used together to treat HIV, with ritonavir making lopinavir more effective.

Who is the study for?
This trial is for adults over 18 with HIV who are virologically suppressed on ART, have a CD4 count above 200 cells/mm^3, and are HPV positive with high-grade anal intraepithelial neoplasia (HGAIN). It's not for those with low-grade AIN, CD4 counts under 200, abnormal lipid profiles, pregnant or breastfeeding women, anyone on chemotherapy/radiation for another cancer or who've had topical therapy for anal dysplasia.
What is being tested?
The study tests the safety of lopinavir/ritonavir in patients living with HIV who have HGAIN. Thirty participants will be involved in active study treatment for about three months and then followed up long-term for an additional forty weeks to monitor effects.
What are the potential side effects?
Potential side effects of lopinavir/ritonavir may include digestive issues like diarrhea and nausea; changes in body fat distribution; increased cholesterol or triglyceride levels; possible liver problems; immune system changes; and potential interactions with other drugs.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
Select...
I am 18 years old or older.
Select...
I have been diagnosed with high-grade anal intraepithelial neoplasia.
Select...
I have tested positive for HPV.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
Select...
I need to take medication that cannot be combined with lopinavir/ritonavir.
Select...
I am unable to understand and give consent for treatment.
Select...
I am currently undergoing chemotherapy or radiation for another cancer.
Select...
I have been diagnosed with low-grade anal dysplasia.
Select...
I have been treated with creams or ointments for anal precancer.
Select...
My cholesterol and triglyceride levels are outside the normal range.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~week 12, week 40
This trial's timeline: 3 weeks for screening, Varies for treatment, and week 12, week 40 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
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)
Heart rate
Secondary study objectives
Number of Participants in the Expansion Cohort Determined clear of HPV by PCR test
Number of Participants in the Expansion Cohort Who Experience Regression of AIN2/3 Determined by Pathology
Human papillomavirus
+4 more

Side effects data

From 2017 Phase 1 trial • 60 Patients • NCT03070470
30%
Headache
20%
Nausea
20%
Atrioventricular Block Second Degree
20%
Skin Reaction
10%
Chalazion
10%
Constipation
10%
Dizziness
10%
Vessel Puncture Site Pain
10%
Vessel Puncture Site Phlebitis
10%
Vessel Puncture Site Swelling
10%
Bradycardia
100%
80%
60%
40%
20%
0%
Study treatment Arm
Dofetilide and Diltiazem
Ranolazine
Verapamil
Lopinavir / Ritonavir
Chloroquine
Placebo

Awards & Highlights

All Individual Drugs Already Approved
Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.
Approved for 5 Other Conditions
This treatment demonstrated efficacy for 5 other conditions.
No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups
Experimental Treatment
Group I: Cohort 4: Lopinavir/Ritonavir 600mg/150mg (3 cycles)Experimental Treatment1 Intervention
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.
Group II: Cohort 3: Lopinavir/Ritonavir 600mg/150mg (2 cycles)Experimental Treatment1 Intervention
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.
Group III: Cohort 2b: Lopinavir/Ritonavir 400mg/100mg (3 cycles)Experimental Treatment1 Intervention
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.
Group IV: Cohort 2: Lopinavir/Ritonavir 400mg/100mg (2 cycles)Experimental Treatment1 Intervention
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.
Group V: Cohort 1b: Lopinavir/Ritonavir 200mg/50mg (3 cycles)Experimental Treatment1 Intervention
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).
Group VI: Cohort 1: Lopinavir/Ritonavir 200mg/50mg (2 cycles)Experimental Treatment1 Intervention
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
First Studied
Drug Approval Stage
How many patients have taken this drug
Ritonavir
FDA approved

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Common treatments for Anal Intraepithelial Neoplasia (AIN) include topical therapies, surgical excision, and antiretroviral therapies such as protease inhibitors. Protease inhibitors like Lopinavir/Ritonavir work by inhibiting the protease enzyme, which is crucial for the maturation of viral particles in HIV. This inhibition can also affect the growth and survival of HPV-infected cells, which are often implicated in AIN. Understanding these mechanisms is important for AIN patients because it highlights the potential for these drugs to not only manage HIV but also reduce the progression of HPV-related neoplasias, offering a dual benefit in treatment.
HIV aspartic peptidase inhibitors are effective drugs against the trypomastigote form of the human pathogen Trypanosoma cruzi.Drug transporter gene expression in human colorectal tissue and cell lines: modulation with antiretrovirals for microbicide optimization.Inhibition of MMP-9 expression by ritonavir or saquinavir is associated with inactivation of the AKT/Fra-1 pathway in cervical intraepithelial neoplasia cells.

Find a Location

Who is running the clinical trial?

Wisconsin Partnership ProgramOTHER
7 Previous Clinical Trials
437 Total Patients Enrolled
University of Wisconsin, MadisonLead Sponsor
1,227 Previous Clinical Trials
3,168,683 Total Patients Enrolled
Evie Carchman, MD, FACSPrincipal InvestigatorUniversity of Wisconsin, Madison

Media Library

Lopinavir / Ritonavir (Protease Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT05334004 — Phase 1
Anal Intraepithelial Neoplasia Research Study Groups: Cohort 2b: Lopinavir/Ritonavir 400mg/100mg (3 cycles), Cohort 1: Lopinavir/Ritonavir 200mg/50mg (2 cycles), Cohort 2: Lopinavir/Ritonavir 400mg/100mg (2 cycles), Cohort 3: Lopinavir/Ritonavir 600mg/150mg (2 cycles), Cohort 1b: Lopinavir/Ritonavir 200mg/50mg (3 cycles), Cohort 4: Lopinavir/Ritonavir 600mg/150mg (3 cycles)
Anal Intraepithelial Neoplasia Clinical Trial 2023: Lopinavir / Ritonavir Highlights & Side Effects. Trial Name: NCT05334004 — Phase 1
Lopinavir / Ritonavir (Protease Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT05334004 — Phase 1
~7 spots leftby Jun 2025