Artesunate Vaginal Inserts for the Treatment of Cervical Intraepithelial Neoplasia (CIN2/3)

Study Overview
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Brief Summary
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This is a phase II double blind, placebo-controlled, randomized study of Artesunate vaginal inserts for the treatment of women who have cervical high grade intraepithelial neoplasia (CIN2/3).

Detailed Description
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Eligible participants in this study are randomized 2:1 to receive either artesunate or placebo vaginal inserts for the treatment of CIN2/3. Both groups receive three 5-day cycles of the respective drug, at weeks 0, 2, and 4. Dosing visits can be done as telehealth visits (medication is mailed to the patient's home). Participants are followed after receiving artesunate at weeks 6, 17, and 40. All participants undergo a LEEP procedure at week 17. Primary Objective: To evaluate the histopathologic response to three 5-day cycles of artesunate vaginal inserts in adult females with biopsy-proven HPV-associated CIN 2/3. Secondary Objectives: To evaluate the safety of artesunate vaginal inserts for the treatment of CIN2/3 To evaluate the viral clearance after three 5-day cycles of artesunate vaginal inserts in adult females with biopsy-proven HPV-associated CIN 2/3. To evaluate viral clearance after three 5-day cycles of artesunate and the LEEP procedure

Official Title
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A Phase II Double Blind, Placebo-controlled, Randomized Trial of Artesunate Vaginal Inserts for the Treatment of Patients With Cervical Intraepithelial Neoplasia (CIN2/3)

Conditions
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CIN 2/3, HPV Infection, Pre-Cancerous Dysplasia, Cervical Dysplasia, HPV Related Disease

Intervention / Treatment
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* Drug: Artesunate vaginal insert
* Drug: Placebo vaginal insert


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult females age ≥ 25 years Capable of informed consent Any HPV genotype detectable by DNA test/HPV genotyping Colposcopically-directed, histologically confirmed tissue diagnosis of cervical high grade squamous intraepithelial lesions (CIN2, CIN3, or CIN2/3) Women of childbearing potential agree to use birth control through week17 of the study. Weight ≥ 50kg Exclusion Criteria: Pregnant and nursing women Active autoimmune disease Taking immunosuppressive medication HIV seropositivity Immunocompromised subjects Evidence of concurrent cervical adenocarcinoma in situ Concurrent malignancy except for nonmelanoma skin lesions, because treatment for other cancers have systemic effects

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 100 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Artesunate vaginal insert<br>Participants will receive three 5-day cycles of artesunate vaginal inserts, 200mg/day, at week 0, week 2, week 4. | Drug: Artesunate vaginal insert<br>* Artesunate formulated as vaginal inserts, 200mg<br>* Other names: artemisinin;|
| Placebo Comparator: Placebo vaginal inserts<br>Participants will receive three 5-day cycles of placebo vaginal inserts, at week 0, week 2, and week 4. | Drug: Placebo vaginal insert<br>* Placebo for artesunate vaginal inserts<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with histologic regression by week 17 | Number of participants who undergo histologic regression to cervical intraepithelial neoplasia (CIN) 1 or less by week 17, following three 5-day cycles of artesunate vaginal inserts, as determined by the LEEP histopathologic analysis | 17 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who have achieved clearance of detectable human papilloma virus (HPV) by week 17 | Number of participants who had HPV strains detected at study entry which become undetectable by week 17 | 17 weeks | 
| Number of participants who have achieved clearance of detectable human papilloma virus (HPV) after three 5-day cycles of artesunate and the LEEP procedure. | Number of participants who had HPV strains detected at study entry which become undetectable after three 5-day cycles of artesunate and the LEEP procedure | 40 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CIN, treatment study, cancer prevention, non-surgical, HPV related disease, topical treatment, vaginal inserts, artesunate, artemisinin, non-invasive, high risk HPV, vaginal suppository