Artesunate Suppositories for the Treatment of HIV-negative Patients With Intra-anal HSIL

Trial Title: Artesunate Suppositories for the Treatment of HIV-negative Patients With Intra-anal HSIL

NCT ID: NCT05555862

Condition: Anal High Grade Squamous Intraepithelial Lesion
Anal Precancerous Condition
AIN 2/3
HPV Infection
Anal Dysplasia
HPV Disease

Conditions: Official terms:
Papillomavirus Infections
Precancerous Conditions
Squamous Intraepithelial Lesions of the Cervix
Carcinoma, Squamous Cell
Carcinoma in Situ
Artesunate
Artenimol
Artemisinins
Artemisinin

Conditions: Keywords:
human papillomavirus
non-surgical
topical treatment
anal HSIL
anal cancer prevention
treatment study
cancer prevention
high-risk HPV
HPV16
suppository

Study type: Interventional

Study phase: Phase 2

Overall status: Active, not recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: Double blind, placebo controlled randomized trial

Primary purpose: Treatment

Masking: Double (Participant, Investigator)

Masking description: Double-blind, placebo-controlled

Intervention:

Intervention type: Drug
Intervention name: Artesunate
Description: artesunate formulated as intra-anal suppositories
Arm group label: Artesunate suppositories

Other name: Artesunic acid

Other name: dihydroartemisinin (DHA)

Other name: artemisinin

Intervention type: Drug
Intervention name: Placebo
Description: placebo intra-anal suppository
Arm group label: Placebo suppositories

Summary: This is a phase II double blind, placebo-controlled, randomized study of Artesunate suppositories for the treatment of HIV-negative men and women who have anal high grade squamous intraepithelial lesions (anal HSIL)

Detailed description: Eligible participants in this study are randomized 2:1 to receive either artesunate or placebo suppositories for the treatment of anal HSIL. Both groups receive four 5-day cycles of suppositories, at weeks 0, 2, 4, and 6. At least two of the dosing visits are done in person. The remaining dosing visits may be done as telehealth visits (suppositories are mailed to the patient's home). Participants are followed closely with anoscopy or high resolution anoscopy (HRA) at weeks 8, 18, 30, and 42. After the week 18 HRA visit, participants who have at least partial response will be followed with HRA at week 30. Participants who are found to be non-responders at week 18 will undergo standard of care ablation. Participants who are found to have anal HSIL at weeks 30 or 42 will be followed according to standard of care procedures. Primary Objective: To evaluate the complete and partial histopathologic response to four 5-day cycles of artesunate suppositories in adult patients with biopsy-proven HPV-associated intra-anal HSIL (18 weeks). Secondary Objectives: Efficacy: - To evaluate the viral clearance after four 5-day cycles of artesunate suppositories in adults with biopsy-proven HPV-associated intra-anal anal HSIL over the study window (42 weeks) - To evaluate complete and partial intra-anal histopathologic response after the week 18 time point but over the study window (30 weeks). - To evaluate complete and partial peri-anal histopathologic response following artesunate suppositories over the course of the study (42 weeks). - To evaluate persistence of response throughout the study window (42 weeks) Safety: To evaluate the safety of artesunate suppositories for the treatment of intra-anal HSIL.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Adult men and women age ≥ 18 years - Capable of informed consent - Biopsy-confirmed intra-anal high-grade dysplasia (AIN 2, AIN 3, anal HSIL) by HRA. Patients must have residual anal HSIL lesions after diagnostic biopsies, as documented by HRA. This includes patients who are newly diagnosed with anal HSIL as well as those who have recurrent anal HSIL after medical therapy or surgical therapy. Patients who have intra-anal HSIL and also have peri-anal HSIL may be enrolled in the study. - Women of childbearing potential agree to use birth control for the duration of the study. - Laboratory values at Screening of: 1. Serum alanine transaminase (SGPT/ALT) < 5 x upper limit of normal (ULN) 2. Serum aspartate transaminase (SGOT/AST) < 5 x ULN 3. Serum Bilirubin (total) < 2.5 x ULN 4. Serum Creatinine ≤ 1.5 x ULN - Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator. - Weight ≥ 50kg Exclusion Criteria: - Pregnant and nursing women - Diagnosis of low-grade anal dysplasia (AIN 1, LSIL), without the concomitant diagnosis of anal HSIL, by HRA - Concurrent anal, vulvar, cervical, or penile cancer - HIV seropositivity - Currently receiving systemic chemotherapy or radiation therapy for another cancer. - Patients who are on medical treatment with systemic immunosuppressants or steroids (e.g., active autoimmune disease) - Concomitant use of strong Uridine glucuronyl transferases (UGT) inhibitors - Concomitant use of imiquimod or 5-fluorouracil (5-FU) for the duration of the study

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Anal Neoplasia and Cancer Research and Education Center

Address:
City: San Francisco
Zip: 94115
Country: United States

Facility:
Name: Anal Dysplasia Clinic MidWest

Address:
City: Chicago
Zip: 60614
Country: United States

Facility:
Name: Laser Surgery Care

Address:
City: New York
Zip: 10011
Country: United States

Start date: February 10, 2023

Completion date: December 31, 2024

Lead sponsor:
Agency: Frantz Viral Therapeutics, LLC
Agency class: Industry

Collaborator:
Agency: Amarex CRO
Agency class: Other

Collaborator:
Agency: University of California, San Francisco
Agency class: Other

Collaborator:
Agency: Anal Dysplasia Clinic MidWest
Agency class: Other

Collaborator:
Agency: Laser Surgery Care
Agency class: Other

Source: Frantz Viral Therapeutics, LLC

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05555862