Phase II Study of Artesunate Ointment for the Treatment of Vulvar High Grade Squamous Intraepithelial Lesions (Vulvar HSIL, VIN2/3)

A Phase II Double-blind, Placebo-controlled, Randomized Trial of Topical Artesunate Ointment for the Treatment of Patients With Vulvar High-grade Squamous Intraepithelial Lesions (Vulvar HSIL)

This is a phase II double-blind, placebo-controlled study of artesunate ointment for the treatment of HPV-associated vulvar HSIL (usual type vulvar intraepithelial neoplasia 2/3).

Eligible participants in this study are randomized 2:1 to receive either artesunate or placebo ointment for the treatment of vulvar HSIL. Both groups receive four 5-day cycles of topical ointment, at weeks 0, 2, 4, and 6. Dosing visits may be done in person or as telehealth (ointment may be shipped directly to the patient). Participants are followed closely with vulvar examinations or colposcopies at weeks 8, 18, 6-months and 12-months.

Inclusion Criteria:

• Adult women age ≥ 18 years

• Capable of informed consent

• Able to collaborate with planned follow-up (transportation, compliance history, etc)

• Biopsy diagnosis of high-grade vulvar dysplasia (VIN2, VIN3, VIN2/3, HSIL), including both new and recurrent disease. A biopsy diagnosis of vulvar high-grade squamous intraepithelial lesion within the previous 3 months which was not excised or otherwise treated may be accepted for study entry.

• Positive HPV test at study entry (any genotype).

• Women of childbearing potential agree to use birth control during the dosing phase (through week 8).

• Laboratory values at Screening of:

  • Serum alanine transaminase (SGPT/ALT) < 5 x upper limit of normal (ULN)
  • Serum aspartate transaminase (SGOT/AST) < 5 x ULN
  • Serum Bilirubin (total) < 2.5 x ULN
  • Serum Creatinine ≤ 1.5 x ULN

• Weight ≥ 50kg

Exclusion Criteria:

• Pregnant and nursing women
• Concurrent anal, vulvar, or cervical cancer
• HIV-positive participants with a CD4 count < 200
• Participants infected with HIV-1 if not on a stable, suppressive antiretroviral therapy (ART) regimen.
• Unwillingness to undergo an excisional procedure at week 18 to either remove HSIL lesions, or to document histologic regression at a site where HSIL was present at study entry.
• Currently receiving systemic chemotherapy or radiation therapy for another cancer.
• Concomitant use of Efavirenz for HIV antiretroviral treatment
• Concomitant use of strong UGT inhibitors
• Concomitant use of imiquimod, cidofovir, or 5-fluorouracil (5-FU) for the duration of the study
• Concurrent dermatological conditions affecting the vulva (e.g., herpetic lesion, Crohn's disease, hidradenitis suppurativa) or vulvar dermatoses (e.g., lichen sclerosis or planus, atopic dermatitis, genital atrophy).
• Concurrent treatment with systemic corticosteroids