Intravaginal Artesunate for the Treatment of HPV+ High Grade Cervical Intraepithelial Neoplasia (CIN2/3)

Phase 1

Completed

• Conditions: Cervical Intraepithelial Neoplasia Grade 2/3; High-risk HPV (Any Strain)
• Interventions: Drug: Artesunate Suppositories

• Registration Number: NCT02354534
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

This phase I research protocol is designed to assess immunogenicity and clinical endpoints in patients with human papillomavirus (HPV) 16 cervical intraepithelial neoplasia (CIN)2/3. The protocol tests the use of artesunate in suppository formulation applied intravaginally in patients with cervical dysplasia (CIN2/3).

The primary endpoint is to determine and evaluate the safety, tolerability, and feasibility of intravaginal administration of artesunate in health women with CIN2/3.

Detailed Description

Phase I open-label dose escalation study of intravaginal artesunate, formulated in suppositories, in adult females with biopsy-confirmed CIN2/3. Thirty (30) subjects will undergo up to a total of three cycles of intravaginal artesunate. The first cycle will be initiated on Day 0, the second at Week 4, and the third and final cycle at week 8.

Study Timeline

• Study First Submitted: 2015-01-13
• Study Start: 2015-02
• Study First Submitted QC: 2015-02-02
• Study First Posted: 2015-02-03
• Primary Completion: 2018-07
• Study Completion: 2018-11-06
• Status Verified: 2021-03
• Results First Submitted: 2021-03-08
• Results First Submitted QC: 2021-03-08
• Results First Posted: 2021-04-02
• Last Update Submitted: 2021-04-06
• Last Update Posted: 2021-04-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

• ≥ 18 years
• Capable of informed consent
• HPV-positive by DNA test
• Histologically confirmed CIN 2, CIN 3, or CIN 2/3
• Body weight ≥ 50 kg
• Immune competent

Exclusion Criteria

• Pregnant and nursing women
• HIV seropositive
• Active autoimmune disease
• Taking immunosuppressive medication
• Evidence of concurrent adenocarcinoma in situ
• Concurrent malignancy except for nonmelanoma skin lesions

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
50 mg Artesunate suppositories, 1 cycle	Artesunate Suppositories	Subjects enrolled in this cohort will receive 1 five day cycle of Artesunate suppositories prior to therapeutic resection of their lesion (if clinically indicated).
200 mg Artesunate suppositories, 1 cycle	Artesunate Suppositories	Subjects enrolled in this cohort will receive 1 five day cycle of Artesunate suppositories prior to therapeutic resection of their lesion (if clinically indicated).
200 mg Artesunate suppositories,2 cycles	Artesunate Suppositories	Subjects enrolled in this cohort will receive 2 five day cycles of Artesunate suppositories prior to therapeutic resection of their lesion (if clinically indicated).
200 mg Artesunate suppositories,3 cycles	Artesunate Suppositories	Subjects enrolled in this cohort will receive 3 five day cycles of Artesunate suppositories prior to therapeutic resection of their lesion (if clinically indicated).

Primary Outcome Measures

Name	Time	Method
Number of Participants With Serious Adverse Events	41 weeks	Number of participants with serious adverse events or dose limiting toxicities related to the study intervention assessed using Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria.

Secondary Outcome Measures

Name	Time	Method
Viral Clearance of HPV	41 weeks	Number of participants whose human papillomavirus (HPV) genotypes present at study entry become undetectable without surgical intervention. HPV genotyping detects strains of HPV present at each timepoint. For this outcome, we evaluated whether strains of HPV detected at study entry became undetectable during the study participation.
Histologic Regression of CIN2/3	41 weeks	Number of participants who had histologic regression from cervical intraepithelial neoplasia (CIN) 2/3 to CIN 1 or less, as assessed by colposcopically-directed biopsies. Histologic regression is defined as disappearance of the high grade lesion (CIN2/3) without surgical intervention.

Trial Locations

Locations (3)

Johns Hopkins Outpatient Center; 🇺🇸 Baltimore, Maryland, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States

Greater Baltimore Medical Center; 🇺🇸 Towson, Maryland, United States