AIN 2/3, Anal Dysplasia, Anal High Grade Squamous Intraepithelial Lesion, Anal Precancerous Condition, HPV Disease, HPV Infection
Conditions
Keywords
human papillomavirus, non-surgical, topical treatment, anal HSIL, anal cancer prevention, treatment study, cancer prevention, high-risk HPV, HPV16, suppository
Brief 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.
Interventions
DRUGArtesunate
artesunate formulated as intra-anal suppositories
DRUGPlacebo
placebo intra-anal suppository
Sponsors
Amarex CRO
University of California, San Francisco
Anal Dysplasia Clinic MidWest
Laser Surgery Care
Frantz Viral Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, 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. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with complete and partial response by week 18 | 18 weeks | Number of participants who achieve complete or partial response after 4 5-day cycles of artesunate as determined by HRA-directed biopsy(ies) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants who have achieved clearance of detectable human papilloma virus (HPV) over the study window | 42 weeks | Number of participants who had HPV strains detected at study entry which become undetectable within the study window |
| Number of participants with complete and partial response after week 18 but over the study window | 30 weeks | Number of participants who achieve complete or partial response after week 18, as documented by HRA-directed biopsy(ies) |
| Number of participants who achieve complete and partial response of peri-anal HSIL, following 4 cycles of intra-anal artesunate suppositories, as determined by HRA-directed biopsy | 42 weeks | Number of participants who had both peri-anal and intra-anal HSIL, whose peri-anal HSIL achieves complete or partial response following 4 cycles of intra-anal artesunate suppositories |
| Number of participants who undergo complete response who maintain their response over the study window | 42 weeks | Number of participants who complete or partial response who maintain this response over the study window |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Treatment-Emergent Adverse Events (TEAE) | 12 weeks | Number of participants who had adverse events, as defined by CTCAE v5.0, related to the study intervention |
| Number of participants who withdrew from the study due to TEAEs | 12 weeks | Number of participants who were withdrawn from the study due to adverse events related to the study drug |
| Changes in vital signs over the study window | 42 weeks | Number of participants who had clinically significant changes in vital signs |
| Changes in physical examination abnormalities | 42 weeks | Number of participants who had clinically significant changes in physical examination abnormalities |
| Clinically significant changes in ECG between baseline and post dosing | 8 weeks | Number of participants who had clinical significant changes in ECG between pre-dosing and post dosing |
Countries
United States
Outcome results
None listed