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
Conditions
Keywords
topical treatment, ointment, non-surgical, vulvar cancer prevention, high-risk HPV, human papillomavirus, HPV, vulvar HSIL, High grade lesions
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.
Interventions
topical ointment, as a non-surgical treatment
DRUGPlacebo ointment
topical placebo ointment
Sponsors
The Cleveland Clinic
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
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with complete histologic response | 18 weeks | Number of participants who have complete histologic response following topical artesunate ointment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Contacts
Primary ContactMihaela Plesa
Backup ContactAhmad Bayat, MD
Outcome results
None listed