Intra-Anally Administered Artesunate in Patients With High-Grade Anal Intraepithelial Neoplasia (AIN 2/3)

Study Overview
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Brief Summary
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This open label study investigates a novel non-surgical approach to the treatment of HPV-associated anal intraepithelial neoplasia, using Artesunate suppositories.

Detailed Description
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Patients diagnosed with AIN 2/3 will be enrolled sequentially in treatment cohorts receiving different doses of Artesunate suppositories administered trans-anally. Doses of escalation will be 200 mg, 400 mg, and 600 mg. Treatment cohorts will consist of 2 or 3 cycles at each dose level. Suppositories will be administered daily for 5 days. Five days constitutes 1 cycle. Up to 3 cycles will be administered at Weeks 0, 2, and 4.

Official Title
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A Phase I Study of Intra-Anally Administered Artesunate in Patients With High-Grade Anal Intraepithelial Neoplasia (AIN 2/3)

Conditions
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HPV-Related Anal Intraepithelial Neoplasia, AIN2/3, Artesunate, Alternative Treatment, Anal Dysplasia, Precancerous Conditions, Human Papilloma Virus

Intervention / Treatment
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* Drug: Artesunate Suppositories


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Biopsy-confirmed high-grade anal dysplasia (AIN 2, AIN 3, HSIL) by high resolution anoscopy (HRA) Female of childbearing potential: negative urine pregnancy test Able to provide informed consent Patients who have the ability to collaborate with planned follow-up (transportation, compliance history, etc.). Weight ≥50 kg. Exclusion Criteria: Diagnosis of low-grade anal dysplasia (AIN 1, LSIL) by high resolution anoscopy Known anal, vulvar, cervical, or penile cancer CD4 count < 200 at the time of consideration for entry into this study Unable to provide informed consent Currently receiving systemic chemotherapy or radiation therapy for another cancer. Patients who are on medical treatment with systemic immunosuppressants or steroids (e.g., active autoimmune disease) Extensive anal condyloma precludes the ability for the clinician to visualize HSIL during HRA

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

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: Sequential Assignment
Interventional Model Description: Subjects will be enrolled sequentially in each treatment cohort.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ART 200 mg, 2 cycles<br>Two five-day cycles of Artesunate suppositories, 200 mg/day | Drug: Artesunate Suppositories<br>* Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia<br>* Other names: Artemisinin;|
| Experimental: ART 200 mg, 3 cycles<br>Three five-day cycles of Artesunate suppositories, 200 mg/day | Drug: Artesunate Suppositories<br>* Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia<br>* Other names: Artemisinin;|
| Experimental: ART 400 mg, 2 cycles<br>Two five-day cycles of Artesunate suppositories, 400 mg/day | Drug: Artesunate Suppositories<br>* Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia<br>* Other names: Artemisinin;|
| Experimental: ART 400 mg, 3 cycles<br>Three five-day cycles of Artesunate suppositories, 400 mg/day | Drug: Artesunate Suppositories<br>* Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia<br>* Other names: Artemisinin;|
| Experimental: ART 600 mg, 2 cycles<br>Two five-day cycles of Artesunate suppositories, 600 mg/day | Drug: Artesunate Suppositories<br>* Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia<br>* Other names: Artemisinin;|
| Experimental: ART 600 mg, 3 cycles<br>Three five-day cycles of Artesunate suppositories, 600 mg/day | Drug: Artesunate Suppositories<br>* Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia<br>* Other names: Artemisinin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (Safety and tolerability) of Artesunate suppositories for the treatment of anal intraepithelial neoplasia (AIN2/3) | Number of patients with serious adverse events or dose limiting toxicities related to the study medication, according to CTCAE4.0 | 6 weeks from the date of the first dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with histologic regression of anal intraepithelial neoplasia (AIN2/3) to AIN1 or less | Number of patients with no AIN2/3 as assessed by high resolution anoscopy and biopsy | 16 weeks | 
| Number of patients with histologic regression of anal intraepithelial neoplasia (AIN2/3) to AIN1 or less | Number of patients with no AIN2/3 as assessed by high resolution anoscopy and biopsy | 28 weeks | 
| Number of patients with viral clearance of human papillomavirus (HPV) virus measured by HPV genotyping | Number of patients with HPV genotypes present at study entry which become undetectable during the study window | 40 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anal precancer, HPV, suppository, Artesunate, artemisinin, anal dysplasia, treatment, alternative treatment, Johns Hopkins, Sandy Fang, Frantz Viral Therapeutics, Wisconsin, Evie Carchman