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

• ClinicalTrials.gov Identifier: NCT03100045
• Recruitment Status: Active, not recruiting
• First Posted: April 4, 2017
• Last Update Posted: April 12, 2021
• Sponsor: Johns Hopkins University
• Collaborators: Frantz Viral Therapeutics, LLC; University of Wisconsin, Madison
• Information provided by (Responsible Party): Johns Hopkins University

Tracking Information

• First Submitted Date: March 29, 2017
• First Posted Date: April 4, 2017
• Last Update Posted Date: April 12, 2021
• Actual Study Start Date: April 20, 2017
• Estimated Primary Completion Date: October 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 22, 2018)

Incidence of treatment-emergent adverse events (Safety and tolerability) of Artesunate suppositories for the treatment of anal intraepithelial neoplasia (AIN2/3) [ Time Frame: 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

Original Primary Outcome Measures (submitted: April 3, 2017)

• Regression of anal intraepithelial neoplasia (AIN2/3) to Anal Intraepithelial Neoplasia (AIN1) or less [ Time Frame: 16 weeks ]
  Clearance of AIN2/3 disease
• Clearance of human papillomavirus (HPV) virus measured by HPV genotyping [ Time Frame: 40 weeks ]
  Clearance of HPV virus in anal specimens collected sequentially

Current Secondary Outcome Measures (submitted: September 27, 2020)

• Number of patients with histologic regression of anal intraepithelial neoplasia (AIN2/3) to AIN1 or less [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 40 weeks ]
  Number of patients with HPV genotypes present at study entry which become undetectable during the study window

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Intra-Anally Administered Artesunate in Patients With High-Grade Anal Intraepithelial Neoplasia (AIN 2/3)
• Official Title: A Phase I Study of Intra-Anally Administered Artesunate in Patients With High-Grade Anal Intraepithelial Neoplasia (AIN 2/3)
• 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 Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Subjects will be enrolled sequentially in each treatment cohort.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

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

Intervention

Drug: Artesunate Suppositories

Artesunate suppositories for the treatment of (AIN2/3) Anal Intraepithelial Neoplasia

Other Name: Artemisinin

Study Arms

• Experimental: ART 200 mg, 2 cycles
  Two five-day cycles of Artesunate suppositories, 200 mg/day
  Intervention: Drug: Artesunate Suppositories
• Experimental: ART 200 mg, 3 cycles
  Three five-day cycles of Artesunate suppositories, 200 mg/day
  Intervention: Drug: Artesunate Suppositories
• Experimental: ART 400 mg, 2 cycles
  Two five-day cycles of Artesunate suppositories, 400 mg/day
  Intervention: Drug: Artesunate Suppositories
• Experimental: ART 400 mg, 3 cycles
  Three five-day cycles of Artesunate suppositories, 400 mg/day
  Intervention: Drug: Artesunate Suppositories
• Experimental: ART 600 mg, 2 cycles
  Two five-day cycles of Artesunate suppositories, 600 mg/day
  Intervention: Drug: Artesunate Suppositories
• Experimental: ART 600 mg, 3 cycles
  Three five-day cycles of Artesunate suppositories, 600 mg/day
  Intervention: Drug: Artesunate Suppositories

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 3, 2017): 18
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 31, 2021
• Estimated Primary Completion Date: October 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03100045
• Other Study ID Numbers: IRB00090922
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Johns Hopkins University
• Study Sponsor: Johns Hopkins University

Collaborators

• Frantz Viral Therapeutics, LLC
• University of Wisconsin, Madison

Investigators

• Principal Investigator: Sandy H Fang, MD; Johns Hopkins University

• PRS Account: Johns Hopkins University
• Verification Date: April 2021