High-Grade Anal Intraepithelial Neoplasia Clinical Trial
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.
| Status | Recruiting |
| Enrollment | 21 |
| Est. completion date | June 2025 |
| Est. primary completion date | June 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. - Lipid profile abnormalities - total cholesterol greater than 240 mg/dL - low density lipoproteins (LDL) greater than 160 mg/dL - high density lipoproteins (HDL) less than 40 mg/dL - triglycerides greater than 500 mg/dL - Have received topical therapy for anal dysplasia previously - Participants who need to take drugs that are contraindicated with lopinavir/ritonavir |
| Country | Name | City | State |
|---|---|---|---|
| United States | UW Digestive Health Center Anoscopy Clinic | Madison | Wisconsin |
| Lead Sponsor | Collaborator |
|---|---|
| University of Wisconsin, Madison | Wisconsin Partnership Program |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | |
| Primary | 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 | 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. | week 12, week 40 | |
| Secondary | Number of Participants in the Expansion Cohort Determined clear of HPV by PCR test | HPV clearance determined by quantitative polymerase chain reaction (PCR) test. | week 12, week 40 | |
| Secondary | 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. | week 12, week 40 | |
| Secondary | Number of Tissue Samples with evidence of autophagy measured by presence of LC3ß and p62 | Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with LC3ß and p62 indicate evidence of autophagy. | week 12, week 40 | |
| Secondary | 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. | week 12, week 40 | |
| Secondary | 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. | week 12, week 40 | |
| Secondary | Number of Tissue Samples with p53 expression | Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). | week 12, week 40 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Not yet recruiting |
NCT04055142 -
Clinical Trial for Evaluating the Efficacy and Safety of Electrocoagulation vs Topic Sinecatechins vs Topic Cidofovir Within the Treatment to High-grade Anal Intraepithelial Neoplasia in HIV Homosexual Males
|
Phase 3 |