Clinical trial NCT06075264: Phase II Study of Artesunate Ointment for the Treatment of Vulvar High Grade Squamous Intraepithelial Lesions (Vulvar HSIL, VIN2/3)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Vulvar Diseases
HPV Infection
Vulvar HSIL
Pre-Cancerous Dysplasia
HPV Disease
VIN, Usual Type
VIN 2 of Usual Type
VIN 3 of Usual Type
Vin II
Vin III
VIN Grade 2
VIN Grade 3
High Grade Intraepithelial Neoplasia
Keywords: topical treatment
ointment
non-surgical
vulvar cancer prevention
high-risk HPV
human papillomavirus
HPV
vulvar HSIL
High grade lesions
Lead sponsor: Frantz Viral Therapeutics, LLC
Sponsor class: INDUSTRY
Collaborators: name: The Cleveland Clinic
First posted: 2023-10-10
Enrollment: 27
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, placebo-controlled randomized trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with complete histologic response
timeFrame: 18 weeks
Secondary outcomes:
measure: Number of participants who have achieved viral clearance
timeFrame: Week 18
measure: Number of participants who show partial response
timeFrame: Week 18
measure: Number of participants who have durable response
timeFrame: Week 18
measure: Incidence of Treatment-Emergent Adverse Events (TEAE)
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Gynecologic Oncology
state: Florida
city: Indianapolis
country: United States
facility: Ascension St. Vincent
state: Indiana
city: Cleveland
country: United States
facility: Cleveland Clinic Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Hospital
state: Ohio
Study officials:
References: