Ignite Creation Date:
2025-12-24 @ 7:55 PM
Ignite Modification Date:
2025-12-25 @ 5:30 PM
Study NCT ID:
NCT05334004
Status:
RECRUITING
Last Update Posted:
2025-05-15
First Post:
2022-04-01
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Lopinavir/Ritonavir in PLWH With High-Grade AIN
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D061466', 'term': 'Lopinavir'}], 'ancestors': [{'id': 'D011744', 'term': 'Pyrimidinones'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'modified 3+3 design with increasing concentrations of study drug and thorough assessment of potential toxicities.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 21}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-12-19', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-05', 'completionDateStruct': {'date': '2026-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-05-13', 'studyFirstSubmitDate': '2022-04-01', 'studyFirstSubmitQcDate': '2022-04-11', 'lastUpdatePostDateStruct': {'date': '2025-05-15', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-04-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'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)', 'timeFrame': 'up to 5 weeks', 'description': '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.'}, {'measure': 'Rate of Grade 3 or above Toxicities in any Organ System in the Escalation Cohorts', 'timeFrame': 'up to 5 weeks', 'description': 'Grade 3 or above as delineated in Common Terminology Criteria for Adverse Events v 5.0 (CTCAE)'}], 'secondaryOutcomes': [{'measure': 'Number of Participants in the Expansion Cohort Who Experience Regression of AIN2/3 Determined by Pathology', 'timeFrame': 'week 12, week 40', 'description': '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.'}, {'measure': 'Number of Participants in the Expansion Cohort Determined clear of HPV by PCR test', 'timeFrame': 'week 12, week 40', 'description': 'HPV clearance determined by quantitative polymerase chain reaction (PCR) test.'}, {'measure': 'Number of Tissue Samples with evidence of apoptosis measured by presence of Activated Caspase 3', 'timeFrame': 'week 12, week 40', 'description': 'Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with activated caspase 3 indicate evidence of apoptosis.'}, {'measure': 'Number of Tissue Samples with evidence of autophagy measured by presence of LC3β and p62', 'timeFrame': 'week 12, week 40', 'description': 'Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with LC3β and p62 indicate evidence of autophagy.'}, {'measure': 'Number of Tissue Samples with evidence of cellular proliferation measured by presence of Ki-67', 'timeFrame': 'week 12, week 40', 'description': 'Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with Ki-67 indicate evidence of cellular proliferation.'}, {'measure': 'Number of Tissue Samples with evidence of HPV positivity measured by presence of p16', 'timeFrame': 'week 12, week 40', 'description': 'Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue). Samples with p16 indicate evidence of HPV positivity.'}, {'measure': 'Number of Tissue Samples with p53 expression', 'timeFrame': 'week 12, week 40', 'description': 'Mechanism of action of protease inhibitors investigated with biomarker studies (immunohistochemistry and Immunofluorescence of tissue).'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['High-Grade Anal Intraepithelial Neoplasia']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nAn expansion cohort of 12 participants will occur at the MTD. Once the MTD is determined, then secondary outcomes will be evaluated.\n\nPrimary Objective\n\n* 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).\n\nSecondary Objectives\n\n* To measure the effect of intra-anal topical lopinavir/ritonavir administration\n* To evaluate clearance of human papillomavirus (HPV)\n* To elucidate the mechanism of action of protease inhibitors'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* willing to provide informed consent\n* greater than or equal to 18 years of age\n* Diagnosis of biopsy-confirmed HGAIN\n* 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\n* willing to comply with all study procedures\n\nExclusion Criteria:\n\n* Diagnosis of low-grade anal dysplasia (AIN, low-grade squamous intraepithelial lesion (LSIL)) by HRA.\n* CD4 count less than 200 cells/mm\\^3 at the time of consideration for entry into the study\n* unable to provide informed consent\n* Pregnant or breastfeeding female\n* Currently receiving systemic chemotherapy or radiation therapy for another cancer.\n* Have received topical therapy for anal dysplasia previously'}, 'identificationModule': {'nctId': 'NCT05334004', 'briefTitle': 'Lopinavir/Ritonavir in PLWH With High-Grade AIN', 'organization': {'class': 'OTHER', 'fullName': 'University of Wisconsin, Madison'}, 'officialTitle': '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)', 'orgStudyIdInfo': {'id': '2023-0052'}, 'secondaryIdInfos': [{'id': 'SMPH/SURGERY/COLON RECT', 'type': 'OTHER', 'domain': 'UW Madison'}, {'id': 'Protocol Version 3/21/2025', 'type': 'OTHER', 'domain': 'UW Madison'}, {'id': '2022-0468 [former]', 'type': 'OTHER', 'domain': 'UW Madison'}, {'id': 'UW22123', 'type': 'OTHER', 'domain': 'UWCCC ID'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Cohort 1: Lopinavir/Ritonavir 200mg/50mg (2 cycles)', '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', 'interventionNames': ['Drug: Lopinavir / Ritonavir']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 1b: Lopinavir/Ritonavir 200mg/50mg (3 cycles)', '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).', 'interventionNames': ['Drug: Lopinavir / Ritonavir']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 2: Lopinavir/Ritonavir 400mg/100mg (2 cycles)', '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.', 'interventionNames': ['Drug: Lopinavir / Ritonavir']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 2b: Lopinavir/Ritonavir 400mg/100mg (3 cycles)', '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.', 'interventionNames': ['Drug: Lopinavir / Ritonavir']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 3: Lopinavir/Ritonavir 600mg/150mg (2 cycles)', '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.', 'interventionNames': ['Drug: Lopinavir / Ritonavir']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 4: Lopinavir/Ritonavir 600mg/150mg (3 cycles)', '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.', 'interventionNames': ['Drug: Lopinavir / Ritonavir']}], 'interventions': [{'name': 'Lopinavir / Ritonavir', 'type': 'DRUG', 'description': 'Human Immunodeficiency Virus (HIV) antiviral, given via suppository', 'armGroupLabels': ['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)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '53705', 'city': 'Madison', 'state': 'Wisconsin', 'status': 'RECRUITING', 'country': 'United States', 'facility': 'UW Digestive Health Center Anoscopy Clinic', 'geoPoint': {'lat': 43.07305, 'lon': -89.40123}}], 'centralContacts': [{'name': 'Cancer Connect, MD, FACS', 'role': 'CONTACT', 'email': 'clinicaltrials@cancer.wisc.edu', 'phone': '800-622-8922'}], 'overallOfficials': [{'name': 'Evie Carchman, MD, FACS', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Wisconsin, Madison'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Wisconsin, Madison', 'class': 'OTHER'}, 'collaborators': [{'name': 'Wisconsin Partnership Program', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}