Artesunate Vaginal Inserts for the Treatment of Cervical Intraepithelial Neoplasia (CIN2/3)

Phase 2

Recruiting

• Conditions: Cervical Dysplasia; HPV Related Disease; HPV Infection; Pre-Cancerous Dysplasia; CIN 2/3
• Interventions: Drug: Artesunate vaginal insert; Drug: Placebo vaginal insert

• Registration Number: NCT04098744
• Lead Sponsor: Frantz Viral Therapeutics, LLC

Brief Summary

This is a phase II double blind, placebo-controlled, randomized study of Artesunate vaginal inserts for the treatment of women who have cervical high grade intraepithelial neoplasia (CIN2/3).

Detailed Description

Eligible participants in this study are randomized 2:1 to receive either artesunate or placebo vaginal inserts for the treatment of CIN2/3. Both groups receive three 5-day cycles of the respective drug, at weeks 0, 2, and 4. Dosing visits can be done as telehealth visits (medication is mailed to the patient's home). Participants are followed after receiving artesunate at weeks 6, 17, and 40. All participants undergo a LEEP procedure at week 17.

Primary Objective: To evaluate the histopathologic response to three 5-day cycles of artesunate vaginal inserts in adult females with biopsy-proven HPV-associated CIN 2/3.

Secondary Objectives:

* To evaluate the safety of artesunate vaginal inserts for the treatment of CIN2/3

* To evaluate the viral clearance after three 5-day cycles of artesunate vaginal inserts in adult females with biopsy-proven HPV-associated CIN 2/3.

* To evaluate viral clearance after three 5-day cycles of artesunate and the LEEP procedure

Study Timeline

• Study First Submitted: 2019-09-19
• Study First Submitted QC: 2019-09-19
• Study First Posted: 2019-09-23
• Study Start: 2020-09-09
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-12
• Last Update Posted: 2024-11-13
• Primary Completion: 2025-07-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 78

Inclusion Criteria

• Adult females age ≥ 25 years
• Capable of informed consent
• Any HPV genotype detectable by DNA test/HPV genotyping
• Colposcopically-directed, histologically confirmed tissue diagnosis of cervical high grade squamous intraepithelial lesions (CIN2, CIN3, or CIN2/3)
• Women of childbearing potential agree to use birth control through week17 of the study.
• Weight ≥ 50kg

Exclusion Criteria

• Pregnant and nursing women
• Active autoimmune disease
• Taking immunosuppressive medication
• HIV seropositivity
• Immunocompromised subjects
• Evidence of concurrent cervical adenocarcinoma in situ
• Concurrent malignancy except for nonmelanoma skin lesions, because treatment for other cancers have systemic effects

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Artesunate vaginal insert	Artesunate vaginal insert	Participants will receive three 5-day cycles of artesunate vaginal inserts, 200mg/day, at week 0, week 2, week 4.
Placebo vaginal inserts	Placebo vaginal insert	Participants will receive three 5-day cycles of placebo vaginal inserts, at week 0, week 2, and week 4.

Primary Outcome Measures

Name	Time	Method
Proportion of participants with histologic regression by week 17	17 weeks	Number of participants who undergo histologic regression to cervical intraepithelial neoplasia (CIN) 1 or less by week 17, following three 5-day cycles of artesunate vaginal inserts, as determined by the LEEP histopathologic analysis

Secondary Outcome Measures

Name	Time	Method
Number of participants who have achieved clearance of detectable human papilloma virus (HPV) by week 17	17 weeks	Number of participants who had HPV strains detected at study entry which become undetectable by week 17
Number of participants who have achieved clearance of detectable human papilloma virus (HPV) after three 5-day cycles of artesunate and the LEEP procedure.	40 weeks	Number of participants who had HPV strains detected at study entry which become undetectable after three 5-day cycles of artesunate and the LEEP procedure

Trial Locations

Locations (7)

Florida Gynecologic Oncology; 🇺🇸 Fort Myers, Florida, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Cleveland Clinic Fairview Hospital; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Hillcrest Hospital; 🇺🇸 Mayfield Heights, Ohio, United States

The Harris Health System (L.B.J Hospital); 🇺🇸 Houston, Texas, United States

University of Texas, M.D. Anderson; 🇺🇸 Houston, Texas, United States