Artesunate Suppositories for the Treatment of HIV-negative Patients With Intra-anal HSIL (anal HSIL HIV-)

A Phase II Double Blind, Placebo-controlled, Randomized Trial of Artesunate Suppositories for the Treatment of HIV-negative Patients With Anal High-grade Squamous Intraepithelial Lesions (Anal HSIL)

This is a phase II double blind, placebo-controlled, randomized study of Artesunate suppositories for the treatment of HIV-negative men and women who have anal high grade squamous intraepithelial lesions (anal HSIL)

Study Overview

• Status: Active, not recruiting
• Conditions: HPV Infection; Anal Dysplasia; Anal High Grade Squamous Intraepithelial Lesion; Anal Precancerous Condition; AIN 2/3; HPV Disease
• Intervention / Treatment: Drug: Artesunate; Drug: Placebo

Detailed Description

Eligible participants in this study are randomized 2:1 to receive either artesunate or placebo suppositories for the treatment of anal HSIL. Both groups receive four 5-day cycles of suppositories, at weeks 0, 2, 4, and 6. At least two of the dosing visits are done in person. The remaining dosing visits may be done as telehealth visits (suppositories are mailed to the patient's home). Participants are followed closely with anoscopy or high resolution anoscopy (HRA) at weeks 8, 18, 30, and 42. After the week 18 HRA visit, participants who have at least partial response will be followed with HRA at week 30.

Participants who are found to be non-responders at week 18 will undergo standard of care ablation.

Participants who are found to have anal HSIL at weeks 30 or 42 will be followed according to standard of care procedures.

Primary Objective: To evaluate the complete and partial histopathologic response to four 5-day cycles of artesunate suppositories in adult patients with biopsy-proven HPV-associated intra-anal HSIL (18 weeks).

Secondary Objectives:

Efficacy:

• To evaluate the viral clearance after four 5-day cycles of artesunate suppositories in adults with biopsy-proven HPV-associated intra-anal anal HSIL over the study window (42 weeks)
• To evaluate complete and partial intra-anal histopathologic response after the week 18 time point but over the study window (30 weeks).
• To evaluate complete and partial peri-anal histopathologic response following artesunate suppositories over the course of the study (42 weeks).
• To evaluate persistence of response throughout the study window (42 weeks)

Safety:

To evaluate the safety of artesunate suppositories for the treatment of intra-anal HSIL.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mihaela Plesa; Phone Number: 440-255-1155; Email: mplesa@frantzgroup.com
• Study Contact Backup: Name: Ahmad Bayat, MD; Phone Number: 301-956-2523; Email: ahmadb@amarexcro.com

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • Anal Neoplasia and Cancer Research and Education Center
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Anal Dysplasia Clinic MidWest
      • Contact: Sarah Coria; Phone Number: 312-623-2625; Email: scoriama@adcmidwest.com
  • New York
    • New York, New York, United States, 10011
      • Laser Surgery Care
      • Sub-Investigator: Joseph Terlizzi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult men and women age ≥ 18 years
• Capable of informed consent
• Biopsy-confirmed intra-anal high-grade dysplasia (AIN 2, AIN 3, anal HSIL) by HRA. Patients must have residual anal HSIL lesions after diagnostic biopsies, as documented by HRA. This includes patients who are newly diagnosed with anal HSIL as well as those who have recurrent anal HSIL after medical therapy or surgical therapy. Patients who have intra-anal HSIL and also have peri-anal HSIL may be enrolled in the study.
• Women of childbearing potential agree to use birth control for the duration of the study.

• Laboratory values at Screening of:

  1. Serum alanine transaminase (SGPT/ALT) < 5 x upper limit of normal (ULN)
  2. Serum aspartate transaminase (SGOT/AST) < 5 x ULN
  3. Serum Bilirubin (total) < 2.5 x ULN
  4. Serum Creatinine ≤ 1.5 x ULN
• Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator.
• Weight ≥ 50kg

Exclusion Criteria:

• Pregnant and nursing women
• Diagnosis of low-grade anal dysplasia (AIN 1, LSIL), without the concomitant diagnosis of anal HSIL, by HRA
• Concurrent anal, vulvar, cervical, or penile cancer
• HIV seropositivity
• 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)
• Concomitant use of strong Uridine glucuronyl transferases (UGT) inhibitors
• Concomitant use of imiquimod or 5-fluorouracil (5-FU) for the duration of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Artesunate suppositories; Four 5-day cycles of artesunate suppositories	Drug: Artesunate; artesunate formulated as intra-anal suppositories; Other Names: Artesunic acid; dihydroartemisinin (DHA); artemisinin
Placebo Comparator: Placebo suppositories; Four 5-day cycles of placebo suppositories	Drug: Placebo; placebo intra-anal suppository

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with complete and partial response by week 18	Number of participants who achieve complete or partial response after 4 5-day cycles of artesunate as determined by HRA-directed biopsy(ies)	18 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who have achieved clearance of detectable human papilloma virus (HPV) over the study window	Number of participants who had HPV strains detected at study entry which become undetectable within the study window	42 weeks
Number of participants with complete and partial response after week 18 but over the study window	Number of participants who achieve complete or partial response after week 18, as documented by HRA-directed biopsy(ies)	30 weeks
Number of participants who achieve complete and partial response of peri-anal HSIL, following 4 cycles of intra-anal artesunate suppositories, as determined by HRA-directed biopsy	Number of participants who had both peri-anal and intra-anal HSIL, whose peri-anal HSIL achieves complete or partial response following 4 cycles of intra-anal artesunate suppositories	42 weeks
Number of participants who undergo complete response who maintain their response over the study window	Number of participants who complete or partial response who maintain this response over the study window	42 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Treatment-Emergent Adverse Events (TEAE)	Number of participants who had adverse events, as defined by CTCAE v5.0, related to the study intervention	12 weeks
Number of participants who withdrew from the study due to TEAEs	Number of participants who were withdrawn from the study due to adverse events related to the study drug	12 weeks
Changes in vital signs over the study window	Number of participants who had clinically significant changes in vital signs	42 weeks
Changes in physical examination abnormalities	Number of participants who had clinically significant changes in physical examination abnormalities	42 weeks
Clinically significant changes in ECG between baseline and post dosing	Number of participants who had clinical significant changes in ECG between pre-dosing and post dosing	8 weeks

Collaborators and Investigators

• Sponsor: Frantz Viral Therapeutics, LLC
• Collaborators: University of California, San Francisco; Laser Surgery Care; Amarex CRO; Anal Dysplasia Clinic MidWest
• Investigators: Principal Investigator: Joel Palefsky, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2023
• Primary Completion (Estimated): February 28, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: September 22, 2022
• First Submitted That Met QC Criteria: September 22, 2022
• First Posted (Actual): September 27, 2022

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: topical treatment; HPV16; human papillomavirus; non-surgical; cancer prevention; suppository; treatment study; anal HSIL; anal cancer prevention; high-risk HPV
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Cervical Diseases; Uterine Diseases; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Neoplasms, Squamous Cell; Uterine Cervical Dysplasia; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Carcinoma in Situ; Carcinoma, Squamous Cell; Precancerous Conditions; Papillomavirus Infections; Squamous Intraepithelial Lesions of the Cervix; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Artesunate; Artenimol; Artemisinins; Artemisinin
• Other Study ID Numbers: ART-AIN IIB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No protected health information (PHI) will be shared with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No