Artesunate Vaginal Inserts for the Treatment of Cervical Intraepithelial Neoplasia (CIN2/3) (ART-CIN_IIB)
Primary Purpose
CIN 2/3, HPV Infection, Pre-Cancerous Dysplasia
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Artesunate vaginal insert
Placebo vaginal insert
Sponsored by
About this trial
This is an interventional treatment trial for CIN 2/3 focused on measuring treatment study, cancer prevention, non-surgical, HPV related disease, CIN, topical treatment, vaginal inserts, artesunate, artemisinin, non-invasive, high risk HPV, vaginal suppository
Eligibility Criteria
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 week 28 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
Sites / Locations
- University of MichiganRecruiting
- Cleveland Clinic Fairview HospitalRecruiting
- Cleveland Clinic FoundationRecruiting
- Hillcrest HospitalRecruiting
- The Harris Health System (L.B.J Hospital)Recruiting
- University of Texas, M.D. AndersonRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Artesunate vaginal insert
Placebo vaginal inserts
Arm Description
Participants will receive three 5-day cycles of artesunate vaginal inserts, 200mg/day, at week 0, week 2, week 4.
Participants will receive three 5-day cycles of placebo vaginal inserts, at week 0, week 2, and week 4.
Outcomes
Primary Outcome Measures
Proportion of participants with histologic regression by week 17
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
Number of participants who have achieved clearance of detectable human papilloma virus (HPV) by week 17
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.
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
Full Information
NCT ID
NCT04098744
First Posted
September 19, 2019
Last Updated
September 7, 2023
Sponsor
Frantz Viral Therapeutics, LLC
Collaborators
Amarex Clinical Research, M.D. Anderson Cancer Center, Harris Health System (L.B.J. Hospital), The Cleveland Clinic, University of Michigan, Morehouse School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT04098744
Brief Title
Artesunate Vaginal Inserts for the Treatment of Cervical Intraepithelial Neoplasia (CIN2/3)
Acronym
ART-CIN_IIB
Official Title
A Phase II Double Blind, Placebo-controlled, Randomized Trial of Artesunate Vaginal Inserts for the Treatment of Patients With Cervical Intraepithelial Neoplasia (CIN2/3)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 9, 2020 (Actual)
Primary Completion Date
July 31, 2024 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Frantz Viral Therapeutics, LLC
Collaborators
Amarex Clinical Research, M.D. Anderson Cancer Center, Harris Health System (L.B.J. Hospital), The Cleveland Clinic, University of Michigan, Morehouse School of Medicine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CIN 2/3, HPV Infection, Pre-Cancerous Dysplasia, Cervical Dysplasia, HPV Related Disease
Keywords
treatment study, cancer prevention, non-surgical, HPV related disease, CIN, topical treatment, vaginal inserts, artesunate, artemisinin, non-invasive, high risk HPV, vaginal suppository
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Participants, study team, and sponsor are blinded to the treatment assignment.
Allocation
Randomized
Enrollment
78 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Artesunate vaginal insert
Arm Type
Experimental
Arm Description
Participants will receive three 5-day cycles of artesunate vaginal inserts, 200mg/day, at week 0, week 2, week 4.
Arm Title
Placebo vaginal inserts
Arm Type
Placebo Comparator
Arm Description
Participants will receive three 5-day cycles of placebo vaginal inserts, at week 0, week 2, and week 4.
Intervention Type
Drug
Intervention Name(s)
Artesunate vaginal insert
Other Intervention Name(s)
Artesunic acid, DHA, artemisinin
Intervention Description
Artesunate formulated as vaginal inserts, 200mg
Intervention Type
Drug
Intervention Name(s)
Placebo vaginal insert
Intervention Description
Placebo for artesunate vaginal inserts
Primary Outcome Measure Information:
Title
Proportion of participants with histologic regression by week 17
Description
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
Time Frame
17 weeks
Secondary Outcome Measure Information:
Title
Number of participants who have achieved clearance of detectable human papilloma virus (HPV) by week 17
Description
Number of participants who had HPV strains detected at study entry which become undetectable by week 17
Time Frame
17 weeks
Title
Number of participants who have achieved clearance of detectable human papilloma virus (HPV) after three 5-day cycles of artesunate and the LEEP procedure.
Description
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
Time Frame
40 weeks
Other Pre-specified Outcome Measures:
Title
Number of participants with Treatment-Emergent Adverse Events (TEAE)
Description
Number of participants who had adverse events, as defined by CTCAE v5.0, related to the study intervention
Time Frame
6 weeks
Title
Number of participants who withdrew from the study due to TEAEs
Description
Number of participants who were withdrawn from the study due to adverse events related to the study drug
Time Frame
6 weeks
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
This study is for women only as it is a treatment for cervical intraepithelial neoplasia (CIN2/3)
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mihaela Plesa, BA, CCRP
Phone
440-255-1155
Ext
100
Email
mplesa@frantzgroup.com
First Name & Middle Initial & Last Name or Official Title & Degree
Ahmad Bayat, MD
Phone
(301) 956-2523
Email
ahmadb@amarexcro.com
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth Haro
Phone
734-277-9808
Email
FAMMED-MISSH@med.umich.edu
First Name & Middle Initial & Last Name & Degree
Diane Harper, MD
Facility Name
Cleveland Clinic Fairview Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44111
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Donna White
Phone
216-445-8090
Email
whited11@ccf.org
First Name & Middle Initial & Last Name & Degree
Megan Park
Phone
216-445-8090
Email
parkm2@ccf.org
First Name & Middle Initial & Last Name & Degree
Chad Michener, MD
First Name & Middle Initial & Last Name & Degree
Mariam AlHilli, MD
First Name & Middle Initial & Last Name & Degree
Steven Waggonner, MD
First Name & Middle Initial & Last Name & Degree
Robert DeBernardo, MD
First Name & Middle Initial & Last Name & Degree
Roberto Vargas, MD
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Donna White
Phone
216-445-8090
Email
whited11@ccf.org
First Name & Middle Initial & Last Name & Degree
Megan Park
Phone
216-445-8090
Email
parkm2@ccf.org
First Name & Middle Initial & Last Name & Degree
Chad Michener, MD
First Name & Middle Initial & Last Name & Degree
Mariam AlHilli, MD
First Name & Middle Initial & Last Name & Degree
Steven Waggonner, MD
First Name & Middle Initial & Last Name & Degree
Robert DeBernardo, MD
First Name & Middle Initial & Last Name & Degree
Roberto Vargas, MD
Facility Name
Hillcrest Hospital
City
Mayfield Heights
State/Province
Ohio
ZIP/Postal Code
44124
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Donna White
Phone
216-445-8090
Email
whited11@ccf.org
First Name & Middle Initial & Last Name & Degree
Megan Park
Phone
216-445-8090
Email
parkm2@ccf.org
First Name & Middle Initial & Last Name & Degree
Chad Michener, MD
First Name & Middle Initial & Last Name & Degree
Mariam AlHilli, MD
First Name & Middle Initial & Last Name & Degree
Steven Waggonner, MD
First Name & Middle Initial & Last Name & Degree
Robert DeBernardo, MD
First Name & Middle Initial & Last Name & Degree
Roberto Vargas, MD
First Name & Middle Initial & Last Name & Degree
Lindsey Beffa, MD
Facility Name
The Harris Health System (L.B.J Hospital)
City
Houston
State/Province
Texas
ZIP/Postal Code
77026
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica Gallegos
Phone
713-563-4580
Email
jrgalleg@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Cindy Melendez
Phone
713-563-4582
Email
cvmelend@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Andrea Milbourne, MD
First Name & Middle Initial & Last Name & Degree
Kathleen Schmeler, MD
Facility Name
University of Texas, M.D. Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica Gallegos
Phone
713-563-4580
Email
jrgalleg@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Cindy Melendez
Phone
713-563-4582
Email
cvmelend@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Andrea Milbourne, MD
First Name & Middle Initial & Last Name & Degree
Kathleen Schmeler, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Artesunate Vaginal Inserts for the Treatment of Cervical Intraepithelial Neoplasia (CIN2/3)
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