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

Phase 1

Completed

• Conditions: HPV-Related Anal Intraepithelial Neoplasia; AIN2/3; Artesunate; Alternative Treatment; Anal Dysplasia; Precancerous Conditions; Human Papilloma Virus
• Interventions: Drug: Artesunate Suppositories

• Registration Number: NCT03100045
• Lead Sponsor: Johns Hopkins University

Brief Summary

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

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 Timeline

• Study First Submitted: 2017-03-29
• Study First Submitted QC: 2017-04-03
• Study First Posted: 2017-04-04
• Study Start: 2017-04-20
• Primary Completion: 2021-10-06
• Study Completion: 2021-10-06
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-02
• Last Update Posted: 2021-11-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ART 600 mg, 3 cycles	Artesunate Suppositories	Three five-day cycles of Artesunate suppositories, 600 mg/day
ART 400 mg, 2 cycles	Artesunate Suppositories	Two five-day cycles of Artesunate suppositories, 400 mg/day
ART 400 mg, 3 cycles	Artesunate Suppositories	Three five-day cycles of Artesunate suppositories, 400 mg/day
ART 600 mg, 2 cycles	Artesunate Suppositories	Two five-day cycles of Artesunate suppositories, 600 mg/day
ART 200 mg, 2 cycles	Artesunate Suppositories	Two five-day cycles of Artesunate suppositories, 200 mg/day
ART 200 mg, 3 cycles	Artesunate Suppositories	Three five-day cycles of Artesunate suppositories, 200 mg/day

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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

Trial Locations

Locations (2)

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

University of Wisconsin Carbone Cancer Center; 🇺🇸 Madison, Wisconsin, United States