Artesunate Ointment for the Treatment of High Grade Vulvar Intraepithelial Neoplasia (HSIL VIN2/3) (ART-VIN)

A Phase I Proof-of-Concept Study of Artesunate Ointment for the Treatment of Patients With High-Grade Vulvar Intraepithelial Neoplasia (HSIL VIN 2/3)

This is a Phase I, proof-of-concept treatment study to evaluate the safety, tolerability and feasibility of topical artesunate ointment to treat high grade vulvar intraepithelial neoplasia (HSIL VIN2/3).

Study Overview

• Status: Completed
• Conditions: Vulvar Diseases; Vulvar Dysplasia; HPV-Related Vulvar Intraepithelial Neoplasia; Preinvasive Vulvar Disease; Vulva Intraepithelial Neoplasia
• Intervention / Treatment: Drug: artesunate ointment 40%

Detailed Description

Phase I open-label dose escalation study of topical artesunate, formulated as ointment, in the treatment of adult females with biopsy-confirmed HSIL VIN2/3. Fifteen (15) subjects will undergo up to a total of three cycles of topical artesunate. The first cycle will be initiated on Day 0, the second at Week 2, and the third and final cycle at week 4.

Primary Objective:

To evaluate the safety and tolerability of artesunate ointment applied topically on VIN2/3 lesions

To measure the effect of artesunate ointment on histologic regression of HSIL/VIN2/3 to VIN1 or less, confirmed by a colposcopically-directed biopsy, at study week 15.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Outpatient Center
  • Ohio
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Fairview Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation - Main Campus
    • Mayfield Heights, Ohio, United States, 44124
      • Cleveland Clinic - Hillcrest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Colposcopically-directed biopsy diagnosis of high-grade vulvar dysplasia (VIN2, VIN3, VIN2/3, HSIL), including both new and recurrent disease.
• Females of childbearing potential: negative urine pregnancy test
• Ability to provide informed consent
• Ability to collaborate with planned follow-up (transportation, compliance history, etc.)
• Use of contraception through the study exit visit (week 28)

Exclusion Criteria:

• Concomitant use of any topical immune modulating agents e.g. imiquimod, Aldara ®
• Cluster of differentiation 4 (CD4) count < 200 at the time of screening for eligibility.
• Unable to provide informed consent
• Currently receiving systemic chemotherapy or radiation therapy for another cancer.
• Pregnant females
• Concurrent dermatological disorders involving the vulva (i.e., herpes, ulceration secondary to Crohn's disease) or vulvar dermatosis (i.e., lichen planus, lichen sclerosus, or lichen simplex chronicus);
• Women weighing less than 50 kg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Artesunate ointment 40%, 1 cycle; Patients enrolled in this treatment group will receive one 5-day cycle of artesunate ointment applied topically to the vulva at week 0.	Drug: artesunate ointment 40%; artesunate formulated as an ointment to be applied topically to the vulva
Experimental: Artesunate ointment 40%, 2 cycles; Patients enrolled in this treatment group will receive two 5-day cycles of artesunate ointment applied topically to the vulva at weeks 0 and 2.	Drug: artesunate ointment 40%; artesunate formulated as an ointment to be applied topically to the vulva
Experimental: Artesunate ointment 40%, 3 cycles; Patients enrolled in this treatment group will receive three 5-day cycles of artesunate ointment applied topically to the vulva at weeks 0, 2, and 4.	Drug: artesunate ointment 40%; artesunate formulated as an ointment to be applied topically to the vulva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of artesunate ointment applied topically on VIN2/3 lesions as assessed by number of participants experiencing serious adverse events or dose-limiting toxicities	Number of participants with study-related serious adverse events or dose-limiting toxicities assessed using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) criteria	15 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of artesunate ointment as assessed by number of participants with regression to VIN1 or less at week 15	Number of participants with histologic regression of HSIL/VIN2/3 to VIN1 or less on colposcopically-directed biopsy, at study week 15 after receiving artesunate ointment therapy.	15 weeks

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Frantz Viral Therapeutics, LLC
• Investigators: Principal Investigator: Cornelia L Trimble, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2019
• Primary Completion (Actual): August 31, 2022
• Study Completion (Actual): December 3, 2024

Study Registration Dates

• First Submitted: January 2, 2019
• First Submitted That Met QC Criteria: January 2, 2019
• First Posted (Actual): January 3, 2019

Study Record Updates

• Last Update Posted (Actual): December 4, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: treatment; non-surgical; alternative; artesunate; cancer prevention; pre-invasive disease
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Genital Diseases, Female; Neoplasms, Glandular and Epithelial; Carcinoma; Neoplasms; Carcinoma in Situ; Vulvar Diseases; Anti-Infective Agents; Antineoplastic Agents; Antiviral Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Artesunate
• Other Study ID Numbers: J18169; IRB00196703 (Other Identifier: Johns Hopkins Medicine); IRB 19 1353 (Other Identifier: Cleveland Clinic Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No