High-Grade Anal Intraepithelial NeoplasiaPhase 1NCT05334004
Lopinavir/Ritonavir in PLWH With High-Grade AIN
A Phase 1 study testing Lopinavir / Ritonavir in people with High-Grade Anal Intraepithelial Neoplasia, run by University of Wisconsin, Madison at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High-Grade Anal Intraepithelial Neoplasia
- What is being tested?
- Lopinavir / Ritonavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Dec 2023to Jun 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UW Digestive Health Center Anoscopy Clinic
Madison, Wisconsin, 53705
About this study
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)
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.
Read the 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
- Being tested
- Lopinavir / Ritonavir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lopinavir / RitonavirDrug
Human Immunodeficiency Virus (HIV) antiviral, given via suppository
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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). Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Lopinavir / Ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: up to 5 weeks
Secondary outcomes (7)
Number of Participants in the Expansion Cohort Who Experience Regression of AIN2/3 Determined by Pathology
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.
Measured: week 12, week 40
Number of Participants in the Expansion Cohort Determined clear of HPV by PCR test
HPV clearance determined by quantitative polymerase chain reaction (PCR) test.
Measured: week 12, week 40
Number of Tissue Samples with evidence of apoptosis measured by presence of Activated Caspase 3
Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with activated caspase 3 indicate evidence of apoptosis.
Measured: week 12, week 40
Number of Tissue Samples with evidence of autophagy measured by presence of LC3β and p62
Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with LC3β and p62 indicate evidence of autophagy.
Measured: week 12, week 40
Number of Tissue Samples with evidence of cellular proliferation measured by presence of Ki-67
Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with Ki-67 indicate evidence of cellular proliferation.
Measured: week 12, week 40
Number of Tissue Samples with evidence of HPV positivity measured by presence of p16
Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with p16 indicate evidence of HPV positivity.
Measured: week 12, week 40
Number of Tissue Samples with p53 expression
Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue).
Measured: week 12, week 40
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2022
- Study start19 Dec 2023
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High-Grade Anal Intraepithelial NeoplasiaStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- modified 3+3 design with increasing concentrations of study drug and thorough assessment of potential toxicities.
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Wisconsin Partnership Program
- Responsible party
- Sponsor
- Investigators
- Evie Carchman, MD, FACS, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05334004
- Sponsor's protocol ID
- 2023-0052
- Other IDs
- SMPH/SURGERY/COLON RECT, Protocol Version 2/24/2026, 2022-0468 [former], UW22123
- Status last verified
- May 2026
- First submitted
- 1 Apr 2022
- Last updated
- 15 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05334004
- Acronym / sponsor ID
- 2023-0052
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Wisconsin Partnership Program
- Study start
- 19 Dec 2023 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 19 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- modified 3+3 design with increasing concentrations of study drug and thorough assessment of potential toxicities.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Lopinavir/Ritonavir 200mg/50mg (2 cycles) | Experimental | Drug: Lopinavir / RitonavirCohort 1 will receive two 5-day cycles of the low dose of the suppository (Lopinavir/Ritonavir (200mg/50mg)) in Weeks 0 and 2 |
| Cohort 1b: Lopinavir/Ritonavir 200mg/50mg (3 cycles) | Experimental | Drug: Lopinavir / RitonavirCohort 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). |
| Cohort 2: Lopinavir/Ritonavir 400mg/100mg (2 cycles) | Experimental | Drug: Lopinavir / RitonavirCohort 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. |
| Cohort 2b: Lopinavir/Ritonavir 400mg/100mg (3 cycles) | Experimental | Drug: Lopinavir / RitonavirCohort 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. |
| Cohort 3: Lopinavir/Ritonavir 600mg/150mg (2 cycles) | Experimental | Drug: Lopinavir / RitonavirCohort 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. |
| Cohort 4: Lopinavir/Ritonavir 600mg/150mg (3 cycles) | Experimental | Drug: Lopinavir / RitonavirCohort 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lopinavir / RitonavirHuman Immunodeficiency Virus (HIV) antiviral, given via suppository | Drug | 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) |
Primary outcome
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.
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)
7 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2026.
- Individual participant dataSharing planned: No
Related trials for High-Grade Anal Intraepithelial Neoplasia
RecruitingPhase 2
CASCADE 2002: PROTECT Study, "PRObiotics to TrEat Anal preCancer Trial
HSIL, High Grade Squamous Intraepithelial Lesion, HPV-Related Squamous Cell Carcinoma
Recruiting
Screening Women With Prior HPV for Anal Neoplasia
HPV-related Lower Genital Tract Neoplasias, HPV-related Anal Neoplasias
Active, not recruiting
Screening Algorithms for Cervical and Anal High-Grade Squamous Intraepithelial Lesions in People With HIV in Mexico and Puerto Rico
AIDS-Related Anal Carcinoma, AIDS-Related Cervical Carcinoma
RecruitingPhase 1
Safety of Anal Curcumin
Anal High Grade Squamous Intraepithelial Lesion
Not yet recruitingPhase 1
Use of ACU-D1 in HPV Associated Vulvar and Perianal Lesions in People With HIV
Human Papilloma Virus, Human Immunodeficiency Virus
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Evie Carchman, MD, FACS principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lopinavir / Ritonavir in people with High-Grade Anal Intraepithelial Neoplasia, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cancer Connect, MD, FACS (800-622-8922, clinicaltrials@cancer.wisc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2026.