Intravaginal Artesunate for the Treatment of HPV+ High Grade Cervical Intraepithelial Neoplasia (CIN2/3)

Study Overview
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Brief Summary
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This phase I research protocol is designed to assess immunogenicity and clinical endpoints in patients with human papillomavirus (HPV) 16 cervical intraepithelial neoplasia (CIN)2/3. The protocol tests the use of artesunate in suppository formulation applied intravaginally in patients with cervical dysplasia (CIN2/3). The primary endpoint is to determine and evaluate the safety, tolerability, and feasibility of intravaginal administration of artesunate in health women with CIN2/3.

Detailed Description
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Phase I open-label dose escalation study of intravaginal artesunate, formulated in suppositories, in adult females with biopsy-confirmed CIN2/3. Thirty (30) subjects will undergo up to a total of three cycles of intravaginal artesunate. The first cycle will be initiated on Day 0, the second at Week 4, and the third and final cycle at week 8.

Official Title
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A Phase I Study of Intravaginally Administered Artesunate In Women With High Grade Cervical Intraepithelial Neoplasia (CIN2/3)

Conditions
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Cervical Intraepithelial Neoplasia Grade 2/3, High-risk HPV (Any Strain)

Intervention / Treatment
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* Drug: Artesunate Suppositories


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years Capable of informed consent HPV-positive by DNA test Histologically confirmed CIN 2, CIN 3, or CIN 2/3 Body weight ≥ 50 kg Immune competent Exclusion Criteria: Pregnant and nursing women HIV seropositive Active autoimmune disease Taking immunosuppressive medication Evidence of concurrent adenocarcinoma in situ Concurrent malignancy except for nonmelanoma skin lesions

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg Artesunate suppositories, 1 cycle<br>Subjects enrolled in this cohort will receive 1 five day cycle of Artesunate suppositories prior to therapeutic resection of their lesion (if clinically indicated). | Drug: Artesunate Suppositories<br> <br> |
| Experimental: 200 mg Artesunate suppositories, 1 cycle<br>Subjects enrolled in this cohort will receive 1 five day cycle of Artesunate suppositories prior to therapeutic resection of their lesion (if clinically indicated). | Drug: Artesunate Suppositories<br> <br> |
| Experimental: 200 mg Artesunate suppositories,2 cycles<br>Subjects enrolled in this cohort will receive 2 five day cycles of Artesunate suppositories prior to therapeutic resection of their lesion (if clinically indicated). | Drug: Artesunate Suppositories<br> <br> |
| Experimental: 200 mg Artesunate suppositories,3 cycles<br>Subjects enrolled in this cohort will receive 3 five day cycles of Artesunate suppositories prior to therapeutic resection of their lesion (if clinically indicated). | Drug: Artesunate Suppositories<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious Adverse Events | Number of participants with serious adverse events or dose limiting toxicities related to the study intervention assessed using Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria. | 41 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral Clearance of HPV | Number of participants whose human papillomavirus (HPV) genotypes present at study entry become undetectable without surgical intervention. HPV genotyping detects strains of HPV present at each timepoint. For this outcome, we evaluated whether strains of HPV detected at study entry became undetectable during the study participation. | 41 weeks | 
| Histologic Regression of CIN2/3 | Number of participants who had histologic regression from cervical intraepithelial neoplasia (CIN) 2/3 to CIN 1 or less, as assessed by colposcopically-directed biopsies. Histologic regression is defined as disappearance of the high grade lesion (CIN2/3) without surgical intervention. | 41 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical dysplasia, HPV, Treatment, preinvasive, cervix, vaginal suppository, Cornelia Trimble, abnormal pap, CIN