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

NCT03100045 — Phase 1, Completed, 18 participants, Johns Hopkins University

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

Registry	NCT03100045, acronym ART-AIN
Status	Completed
Phase	Phase 1
Study type	Interventional; non randomized, sequential, masking: none, treatment
Enrollment	18 (Actual)
Sponsor	Johns Hopkins University (Other); collaborators: Frantz Viral Therapeutics, LLC, University of Wisconsin, Madison
Conditions	HPV-Related Anal Intraepithelial Neoplasia, AIN2/3, Artesunate, Alternative Treatment, Anal Dysplasia, Precancerous Conditions, Human Papilloma Virus
Interventions	Artesunate Suppositories (Drug)
Dates	start 2017-04-20, primary completion 2021-10-06, completion 2021-10-06, first posted 2017-04-04, last updated 2021-11-03
Locations	2 sites in United States

-Summary

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

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+Detailed description

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.

+Arms and interventions

Arm	Type	Interventions	Description
ART 200 mg, 2 cycles	Experimental	Drug: Artesunate Suppositories	Two five-day cycles of Artesunate suppositories, 200 mg/day
ART 200 mg, 3 cycles	Experimental	Drug: Artesunate Suppositories	Three five-day cycles of Artesunate suppositories, 200 mg/day
ART 400 mg, 2 cycles	Experimental	Drug: Artesunate Suppositories	Two five-day cycles of Artesunate suppositories, 400 mg/day
ART 400 mg, 3 cycles	Experimental	Drug: Artesunate Suppositories	Three five-day cycles of Artesunate suppositories, 400 mg/day
ART 600 mg, 2 cycles	Experimental	Drug: Artesunate Suppositories	Two five-day cycles of Artesunate suppositories, 600 mg/day
ART 600 mg, 3 cycles	Experimental	Drug: Artesunate Suppositories	Three five-day cycles of Artesunate suppositories, 600 mg/day

Artesunate Suppositories (Drug), also known as Artemisinin: Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia

+Outcome measures

Primary outcomes

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

Secondary outcomes

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

+Eligibility

Sex: All, ages: 18 Years to 100 Years

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

+Locations (2)

Facility	City	Country	Status
Johns Hopkins Hospital	Baltimore, Maryland	United States
University of Wisconsin Carbone Cancer Center	Madison, Wisconsin	United States

+Investigators

Sandy H Fang, MD, Principal investigator, Johns Hopkins University