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

A Phase II Double Blind, Placebo-controlled, Randomized Trial of Artesunate Suppositories for the Treatment of HIV-negative Patients With Anal High-grade Squamous Intraepithelial Lesions (Anal HSIL)

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)

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.

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