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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202011810125237 Date of Registration: 26/11/2020
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Kisumu Combined Ring Study
Official scientific title Phase IIa, 90-Day Safety, Adherence, and Acceptability Study of Intravaginal Rings Releasing Tenofovir with and without Levonorgestrel among Women in Western Kenya
Brief summary describing the background and objectives of the trial This study is a Phase IIa, randomized, placebo-controlled, three-arm trial to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, acceptability, and adherence to a novel 90-day MPT intravaginal ring (TFV/LNG) and a 90-day single agent IVR (TFV only). A total of approximately 50 eligible participants at a single study site will be randomized 2:2:1 to receive TFV/LNG, TFV only, or placebo IVR. Participants are expected to complete ten (10) unique scheduled study visits and one (1) follow-up contact, where primary and secondary endpoints will be collected over a follow-up period of approximately 4-5 months after randomization and initiation of the IVR.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations,Obstetrics and Gynecology,Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied Fertility-female,HIV/AIDS
Purpose of the trial Prevention
Anticipated trial start date 08/06/2018
Actual trial start date
Anticipated date of last follow up 21/06/2019
Actual Last follow-up date
Anticipated target sample size (number of participants) 50
Actual target sample size (number of participants)
Recruitment status Completed
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
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Tenofovir disoproxil fumarate and Levonorgestrel TFV/LNG IVR (1.15g/6.0mg), delivering 8-10mg/20μg daily 90 days Intra Vaginal Ring 20
Experimental Group Tenofovir 1.41g delivering 8-10mg daily 8-10mg daily Intra vaginal Ring 20
Control Group Placebo Non Eluting 90 days Intra Vaginal Ring 10 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Female, aged 18-34 years, inclusive • General good health (by history and per clinician discretion) without any clinically significant systemic disease (including, but not limited to significant liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease, osteoporosis or bone disease, and diabetes), uterus, and cervix • Not pregnant or planning to become pregnant • Pre-screening (Visit 0) HIV risk score ≤4 (on HIV risk assessment tool developed for women in sub-Saharan Africa (included in Appendix II) • Currently having regular menstrual cycles (approximately 24-35 days) OR with a history of having regular menstrual cycles before contraceptive use, by report, and resumed some menstruation or spotting (with biochemical confirmation of ovulation) • Willing to undergo Visual Inspection with Lugol’s Iodine (VILI) for cervical abnormalities during pelvic exam at Visit 1 o Women with an abnormal VILI will be linked directly to cervical cancer screening through Papanicolaou smear testing and will not be eligible for enrollment unless cervical cancer screening is negative • Willing to abstain from use of vaginal products other than the study product, including tampons (except for during menses) , menstrual cups, vaginally inserted cloths or other materials, spermicides, lubricants, and douches for the whole study • Willing to abstain from any vaginal intercourse starting 48 hours before CM collection, as possible, and 48 hours before Visits 4 and 7 • Vaginal and cervical anatomy that, in the opinion of the clinician, lends itself to easy genital tract sample collection and is absent of vesicles and ulcers • No use of hormonal contraceptives within the following periods specified for each type of contraception method: o Oral contraceptives (combined or progestin-only), contraceptive patch or contraceptive vaginal ring at least two (2) months prior to Visit 1 o Last DMPA injection received at least four (4) months prior to Visit 1 and has resumed re • Body mass index (BMI) ≥30 kg/m • History of hysterectomy • Currently pregnant or within less than three (3) calendar months of the last pregnancy outcome. Note: If recently pregnant, must have had at least two spontaneous menses since pregnancy outcome • Currently breastfeeding or having breastfed an infant in the last two (2) months, or planning to breastfeed during the course of the study • Contraindication to any study products—LNG, TFV, or excipient ingredients • Contraindication to LNG (detailed in Appendix VI and the standard operating procedures (SOP) manual, which is consistent with WHO guidelines http://apps.who.int/iris/bitstream/10665/181468/1/9789241549158_eng.pdf?ua=1 • In the last three (3) months, diagnosed with or treated for any STI or pelvic inflammatory disease o Note: Women with a history of genital herpes or condylomata who have been asymptomatic for at least six (6) months may be considered for eligibility if pelvic exam shows no vesicles or open lesions. • Positive test for HIV-1 (in accordance with national testing algorithm, Appendix IV), syphilis, Trichomonas vaginalis (TV), Neisseria gonorrhea (GC), Chlamydia trachomatis (CT) or HBsAg o NOTE: Women who test positive for HIV-1, syphilis, TV, GC, or CT will be treated for the STI at no cost at the CRC according to the 2015 Kenya National AIDS and STI Control Programme Algorithms for Managing Common STI Syndromes (https://aidsfree.usaid.gov/sites/default/files/hts_policy_kenya_2015.pdf); they will also receive face-to-face counseling, but will not be eligible to take part in the study. • Nugent score greater than or equal to 7 or a symptomatic BV clinical diagnosis as defined by Amsel’s criteria o Must have 3 of the 4 signs for a diagnosis of BV using Amsel’s criteria  Discharge, white & homogeneous  Elevated pH, >4.5  Amine odor present  20% clue cells present on wet mount • Chronic or acute vulvar or vaginal symptoms (pain, irritation, spotting/bleeding, discharge, etc.) Adolescent: 13 Year(s)-17 Year(s),Adult: 18 Year(s)-44 Year(s) 18 Year(s) 34 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 08/06/2018 KEMRI Scientifics and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
Nairobi, off Mbagathi way Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To evaluate genital and systemic safety of the TFV/LNG and TFV IVRs compared to the placebo during and after 90-days of use among women in Western Kenya end of study
Secondary Outcome • Pharmacokinetics (PK) and pharmacodynamics (PD) of the IVR active pharmaceutical agents o To evaluate PK of TFV o To evaluate PK of LNG o To evaluate PD surrogate markers of contraceptive efficacy of LNG o To evaluate PD surrogate markers of microbicidal efficacy of TFV • To assess biological (microbiological/immunological) effects of IVRs on the female genital tract • To assess subjective and objective measures of tolerability • To assess subjective and objective measures of adherence • To assess acceptability (through quantitative data collection methods end of study
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kenya Medical Research Institute Kisumu Clinical Research Site JOOTRH Hospital Off Kakamega road PO BOX 1578 40100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
United States Agency for International Development 1001 Pennsylvania Ave NW Washington, DC Washington 20004 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor United States Centers for Disease Control and Prevention 1600 Clifton Rd., MS-E45, Atlanta Atlanta 30333 United States of America Funding Agency
COLLABORATORS
Name Street address City Postal code Country
Kenya Medical Research Institute Center for Global Health Research Kisumu, Off Kakakmega Road Kisumu 40100 Kenya
University Of washington Global Health, International Clinical Research Center 325 9th Avenue Seattle 98104 United States of America
CONRAD 1911 North Fort Myer Drive Arlington suite 900 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Victor Mudhune Vmudhune@kemricdc.org +254722687430 Kisumu, off Kakamega Road
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya Pharmacist
Role Name Email Phone Street address
Public Enquiries Beatrice Nyagol bnyagol@kemricdc.org +254720582681 Kisumu along Kakakmega road
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya Study Clinician
Role Name Email Phone Street address
Scientific Enquiries Beatrice Njoroge Betnjoroge@yahoo.com +254722800693 Mbagathi way Nairobi
City Postal code Country Position/Affiliation
Nairobi 40100 Kenya Medical Officers
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes CONRAD will share some study findings with the US FDA in advance of their dissemination to all other sources. Findings of this study will then be shared with study participants, members of the local community, at professional conferences, and in peer-reviewed journals, as appropriate. Publication of the results of this study will be governed by CONRAD and CDC policies. Any presentation, abstract, or manuscript will be submitted to CONRAD and CDC for review prior to submission. Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol Sharing of data will begin immediately after the data analyisis is complete, this is after approximately 1 year of study completion A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by United States Law. This website will not include information that can identify you. At most, the website will include a summary of the results. You can search this website at any time.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
http://www.ClinicalTrials.gov 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