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

Sponsor

Frantz Viral Therapeutics, LLC (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06075264

Collaborator

The Cleveland Clinic (Other)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Artesunate ointment Drug: Placebo ointment	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

27 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double-blind, placebo-controlled randomized trialDouble-blind, placebo-controlled randomized trial

Masking:

Double (Participant, Investigator)

Masking Description:

Double-blind, placebo controlled

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Artesunate ointment Artesunate formulated as topical ointment, 40% Four 5-day cycles of artesunate ointment every 2 weeks	Drug: Artesunate ointment topical ointment, as a non-surgical treatment Other Names: Artesunic acid Dihydroartemisinin (DHA) Artemisinin
Placebo Comparator: Placebo ointment Placebo ointment Four 5-day cycles of placebo ointment every 2 weeks	Drug: Placebo ointment topical placebo ointment Other Names: Placebo to artesunate ointment

Arm

Intervention/Treatment

Active Comparator: Artesunate ointment

Artesunate formulated as topical ointment, 40% Four 5-day cycles of artesunate ointment every 2 weeks

Drug: Artesunate ointment

topical ointment, as a non-surgical treatment

Other Names:

Artesunic acid

Dihydroartemisinin (DHA)

Artemisinin

Placebo Comparator: Placebo ointment

Placebo ointment Four 5-day cycles of placebo ointment every 2 weeks

Drug: Placebo ointment

topical placebo ointment

Other Names:

Placebo to artesunate ointment

Outcome Measures

Primary Outcome Measures

Number of participants with complete histologic response [18 weeks]
Number of participants who have complete histologic response following topical artesunate ointment

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Fairview Hospital	Cleveland	Ohio	United States	44111
2	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
3	Hillcrest Hospital	Mayfield Heights	Ohio	United States	44124