Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202402687748210 Date of Approval: 02/02/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title IGHID 12333 Study
Official scientific title IGHID 12333: Phase I study on the Pharmacokinetics of intravaginal, self-administered Artesunate vaginal pessaries among women in Kenya
Brief summary describing the background and objectives of the trial Lack of access to precancer treatment following screening in LMICs in part accounts for the high burden of incident cervical cancer. Preclinical data have demonstrated pro-apoptotic effects of Artesunate (AS), a commonly available drug with an excellent safety profile in oral, rectal and intravenous routes primarily used to treat malaria in LMICS. This led to a recent Phase I study in the United States that demonstrated that self-administered vaginal artesunate inserts (pessaries) are safe, well-tolerated, and demonstrate efficacy for treatment of CIN2/3. Based on the mechanism of action, the clinical safety profile, and widespread availability as a generic drug on the World Health Organization (WHO) List of Essential Medications, vaginal artesunate inserts (pessaries), if backed by data from randomized trials, may offer patient-controlled and access cervical precancer treatment method for women in LMICs who face the greatest burden of cervical cancer and have difficulty accessing skilled providers for precancer treatment. However, given that artesunate is a well-known drug used in malaria treatment, it is critical to ensure that vaginal application of the drug will not promote resistance for use in malaria treatment. Objectives: The proposed study seeks to investigate the pharmacokinetics of Artesunate (AS) and dihydroartemisinin (DHA), the active metabolite of artesunate, following intravaginal use at the dosing and frequency being studied for cervical precancer treatment. A secondary objective is to investigate safety among study participants.
Type of trial Non-Randomised
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Cancer
Sub-Disease(s) or condition(s) being studied
Purpose of the trial To determine the pharmacokinetic prophile of artesunate
Anticipated trial start date 01/04/2024
Actual trial start date
Anticipated date of last follow up 01/07/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 12
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Single Group Non-randomised Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Artesunate vaginal inserts 200 mg daily for five consecutive days 5 days Participants will self-administer 200 mg Artesunate vaginal insert (pessary) once a day for 5 consecutive days 12
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
- Age 18 years to 65 years - Negative pregnancy test at screening - Weight ≥50 Kg at study entry* - Willingness to use contraception (hormonal or barrier) during the 5-day study dosing phase if of childbearing age (less than 50 years of age) - Ability and willingness to provide informed consent - Plan to reside in the study location during the study period - Agrees for samples without identifiers to be shipped outside of Kenya for testing *Justification for weight criteria: A minimum body weight of 50Kg will meet the planned artesunate dosing of ≤4 mg/Kg for which excellent safety data is available. - Current pregnancy or breastfeeding status - History of total hysterectomy - Known allergy to Artesunate - Have a medical comorbidity that in the opinion of the investigator would interfere with study participation - Currently receiving artemisinin-based agents for malaria treatment or completed artemisinin-based treatment within the previous 3 days.* - Male at birth - Current use of efavirenz antiretroviral therapy - Positive malaria antigen test at screening *Based on dihydroartesunate (artesunate’s active metabolite) half-life of between 0.5-1.5 hours Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 65 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 19/01/2024 Amref Ethics and Scientific Review Committee
Ethics Committee Address
Street address City Postal code Country
Wilson Airport Nairobi Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Plasma concentration versus time curve (AUC) of dihydroartemisinin (DHA) following five consecutive days of self-administration of 200mg Artesunate vaginal inserts (pessaries) among healthy women in Kenya. On day 5 of dosing
Secondary Outcome 1. Plasma AUC of Artesunate following 5-day self-administration of 200mg Artesunate vaginal inserts (pessaries) 2. Maximum concentration of Artesunate (Cmax) following 5-day self-administration of 200mg Artesunate vaginal inserts (pessaries) On day 5 of dosing
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kenya Medical Research Institute Research Care and Training Program Lumumba Subcounty Hospital Kisumu Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
University of North Carolina Chapel Hill Department of Obstetrics and Gynecology 3009 Old Clinic Building Campus Box 7570 Chapel Hill NC 27599 Chapel Hill United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of North Carolina Chapel Hill Department of Obstetrics and Gynecology 3009 Old Clinic Building Campus Box 7570 Chapel Hill NC 27599 Chapel Hill NC United States of America University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Chemtai Mungo Chemtai_mungo@med.unc.edu +19199666049 3009 Old Clinic Building Campus Box 7570 Chapel Hill NC 27599
City Postal code Country Position/Affiliation
Chapel Hill NC United States of America Principal Investigator
Role Name Email Phone Street address
Public Enquiries Cirilus Ogollah cogollah@kemri-rctp.org +254724717472 Lumumba Subcounty Hospital
City Postal code Country Position/Affiliation
Kisumu Kenya Co Investigator
Role Name Email Phone Street address
Scientific Enquiries Chemtai Mungo Chemtai_mungo@med.unc.edu +19199666049 3009 Old Clinic Building Campus Box 7570 Chapel Hill NC 27599
City Postal code Country Position/Affiliation
Chapel Hill NC United States of America Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data that underlie the results reported in this article, after de-identification (text,tables,figures, and appendices) will be available.The Clinical study report will be available for researchers who provide a methodologically sound proposal immediately after study publication.This data shall only be used to achieve aims in the approved protocols. Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol Within 12 months of the study completion date Controlled
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information