Anal High-grade Squamous Intraepithelial Lesion, Anal HSIL, Anal HPV Infection, AIN
Conditions
Keywords
intra-anal, topical, non-surgical
Brief summary
This is a phase II double blind, placebo-controlled, randomized study of artesunate ointment 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 ointment for the treatment of anal HSIL. Both groups receive four 5-day cycles of ointment, at weeks 0, 2, 4, and 6. 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 ointment 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 ointment To evaluate complete and partial intra-anal response To evaluate complete and partial peri-anal response To evaluate persistence of response throughout the study window Safety: To evaluate the safety of artesunate ointment for the treatment of intra-anal HSIL.
Interventions
Four 5-day cycles of artesunate ointment given at weeks 0, 2, 4, 6
DRUGPlacebo
Four 5-day cycles of placebo ointment given at weeks 0, 2, 4, 6
Sponsors
Laser Surgery Care, LLC
Anal Dysplasia Clinic MidWest
Frantz Viral Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-blind, placebo-controlled
Intervention model description
Double blind, placebo-controlled randomized trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. * Positive anal human papillomavirus (HPV) test. * 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). Participants using nasal steroid treatments for allergic conditions may participate in the study. * Concomitant use of strong UGT (Uridine-diphosphate-glucuronosyltransferase) inhibitors * Concomitant use of imiquimod or 5-fluorouracil (5-FU) for the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete and partial response by week 18 | 18 weeks | Number of participants with complete and partial response after four 5-day cycles of artesunate ointment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HPV clearance | 42 weeks | Number of participants who do not have detectable HPV infection |
| Complete and partial response after week 18 | 30 weeks | Number of participants with complete and partial response after week 18 |
| Complete and partial peri-anal response after intra-anal ointment application | 42 weeks | Number of participants who have complete and partial peri-anal response after 4 5-day cycles of intra-anal ointment |
| Persistence of response | 42 weeks | Number of participants who have complete response and do not have recurrence of anal HSIL |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety of intra-anal artesunate ointment | 42 weeks | Number of participants who do not have any drug-related serious adverse events |
Countries
United States
Contacts
Primary ContactMihaela Plesa
Backup ContactAhmad Bayat, MD
Outcome results
None listed