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

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

• Artesunate vaginal insert (Drug), also known as Artesunic acid, DHA, artemisinin: Artesunate formulated as vaginal inserts, 200mg
• Placebo vaginal insert (Drug): Placebo for artesunate vaginal inserts

Primary outcomes

• 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 outcomes

• 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

Other outcomes

• Number of participants with Treatment-Emergent Adverse Events (TEAE) [6 weeks]: Number of participants who had adverse events, as defined by CTCAE v5.0, related to the study intervention
• Number of participants who withdrew from the study due to TEAEs [6 weeks]: Number of participants who were withdrawn from the study due to adverse events related to the study drug

Sex: Female, ages: 25 Years to 100 Years

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