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

A Phase I Study of Intravaginally Administered Artesunate In Women With High Grade Cervical Intraepithelial Neoplasia (CIN2/3)

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Outpatient Center
    • Towson, Maryland, United States, 21204
      • Greater Baltimore Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious Adverse Events	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.	41 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral Clearance of HPV	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.	41 weeks
Histologic Regression of CIN2/3	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.	41 weeks

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Frantz Viral Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): November 6, 2018

Study Registration Dates

• First Submitted: January 13, 2015
• First Submitted That Met QC Criteria: February 2, 2015
• First Posted (Estimate): February 3, 2015

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Treatment; cervical dysplasia; HPV; CIN; cervix; vaginal suppository; preinvasive; Cornelia Trimble; abnormal pap
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms; Carcinoma in Situ; Cervical Intraepithelial Neoplasia; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Artesunate
• Other Study ID Numbers: J1498; IRB00045376 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No