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

Sponsor

Johns Hopkins University (Other)

Overall Status

Completed

CT.gov ID

NCT03100045

Collaborator

Frantz Viral Therapeutics, LLC (Industry), University of Wisconsin, Madison (Other)

Enrollment

Locations

Arms

53.6

Actual Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
HPV-Related Anal Intraepithelial Neoplasia AIN2/3 Artesunate Alternative Treatment Anal Dysplasia Precancerous Conditions Human Papilloma Virus	Drug: Artesunate Suppositories	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Subjects will be enrolled sequentially in each treatment cohort.Subjects will be enrolled sequentially in each treatment cohort.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 20, 2017

Actual Primary Completion Date :

Oct 6, 2021

Actual Study Completion Date :

Oct 6, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ART 200 mg, 2 cycles Two five-day cycles of Artesunate suppositories, 200 mg/day	Drug: Artesunate Suppositories Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia Other Names: Artemisinin
Experimental: ART 200 mg, 3 cycles Three five-day cycles of Artesunate suppositories, 200 mg/day	Drug: Artesunate Suppositories Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia Other Names: Artemisinin
Experimental: ART 400 mg, 2 cycles Two five-day cycles of Artesunate suppositories, 400 mg/day	Drug: Artesunate Suppositories Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia Other Names: Artemisinin
Experimental: ART 400 mg, 3 cycles Three five-day cycles of Artesunate suppositories, 400 mg/day	Drug: Artesunate Suppositories Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia Other Names: Artemisinin
Experimental: ART 600 mg, 2 cycles Two five-day cycles of Artesunate suppositories, 600 mg/day	Drug: Artesunate Suppositories Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia Other Names: Artemisinin
Experimental: ART 600 mg, 3 cycles Three five-day cycles of Artesunate suppositories, 600 mg/day	Drug: Artesunate Suppositories Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia Other Names: Artemisinin

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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