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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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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

Intervention / Treatment
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* Drug: Artesunate ointment
* Drug: Placebo ointment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, placebo-controlled randomized trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Artesunate ointment<br>Artesunate formulated as topical ointment, 40% Four 5-day cycles of artesunate ointment every 2 weeks | Drug: Artesunate ointment<br>* topical ointment, as a non-surgical treatment<br>* Other names: Artemisinin;|
| Placebo Comparator: Placebo ointment<br>Placebo ointment Four 5-day cycles of placebo ointment every 2 weeks | Drug: Placebo ointment<br>* topical placebo ointment<br>* Other names: Placebo to artesunate ointment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with complete histologic response | Number of participants who have complete histologic response following topical artesunate ointment | 18 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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topical treatment, ointment, non-surgical, vulvar cancer prevention, high-risk HPV, human papillomavirus, HPV, vulvar HSIL, High grade lesions