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

Phase 2

Recruiting

• Conditions: HPV Infection; VIN 3 of Usual Type; VIN Grade 2; VIN Grade 3; High Grade Intraepithelial Neoplasia; Vulvar Diseases; Vulvar HSIL; VIN 2 of Usual Type; Vin II; Vin III
• Interventions: Drug: Artesunate ointment; Drug: Placebo ointment

• Registration Number: NCT06075264
• Lead Sponsor: Frantz Viral Therapeutics, LLC

Brief Summary

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).

Detailed Description

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.

Study Timeline

• Study First Submitted: 2023-10-04
• Study First Submitted QC: 2023-10-04
• Study First Posted: 2023-10-10
• Study Start: 2023-12-06
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-17
• Last Update Posted: 2024-12-19
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 27

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Artesunate ointment	Artesunate ointment	Artesunate formulated as topical ointment, 40% Four 5-day cycles of artesunate ointment every 2 weeks
Placebo ointment	Placebo ointment	Placebo ointment Four 5-day cycles of placebo ointment every 2 weeks

Primary Outcome Measures

Name	Time	Method
Number of participants with complete histologic response	18 weeks	Number of participants who have complete histologic response following topical artesunate ointment

Secondary Outcome Measures

Name	Time	Method
Number of participants who have achieved viral clearance	Week 18	Number of participants who achieve clearance of HPV genotypes present at screening. These genotypes become undetectable over the study window.
Number of participants who show partial response	Week 18	Number of participants with documented partial response following topical artesunate
Number of participants who have durable response	Week 18	Number of participants with documented complete response who do not have recurrence of their vulvar HSIL over the study window
Incidence of Treatment-Emergent Adverse Events (TEAE)	8 weeks	Number of participants who report artesunate-related serious adverse events

Trial Locations

Locations (5)

Florida Gynecologic Oncology; 🇺🇸 Fort Myers, Florida, United States

Ascension St. Vincent; 🇺🇸 Indianapolis, Indiana, United States

Cleveland Clinic Fairview Hospital; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Hillcrest Hospital; 🇺🇸 Mayfield Heights, Ohio, United States