HIVPhase 2NCT03762382
Tenofovir/Levonorgestrel Intravaginal Ring and Tenofovir Intravaginal Ring
A Phase 2 study testing TFV/LNG IVR and TFV IVR in people with HIV and Contraception, run by CONRAD at 1 site in Kenya.
Trial summary
The purpose of the study is to evaluate the safety, pharmacokinetics and pharmacodynamics of, and the tolerability and acceptance of an intravaginal ring (IVR) delivering both tenofovir and levonorgestrel (TFV/LNG) and an IVR delivering TFV only, compared to a placebo IVR, in women in Western Kenya. Read more about this study
- Who is it for?
- Ages 18 to 34 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV, Contraception, Prevention
- What is being tested?
- TFV/LNG IVR and TFV IVR
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteKenya
- Study dates
- 12 Dec 2018to Apr 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 34 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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 HIV risk score ≤4
- 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
Show all 19Show fewer
- 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 certain study visits
- 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:
- Oral contraceptives (combined or progestin-only), contraceptive patch or contraceptive vaginal ring in at least two (2) months
- Last DMPA injection received at least four (4) months ago and has resumed regular menstruation
- Hormonal IUD/IUS removed at least four (4) months ago and has resumed regular menstruation
- Hormonal implant removed at least six (6) months ago and has resumed regular menstruation
- Willing to refrain from using any hormonal contraceptives for the entire study and to use only study-provided non-spermicidal male condoms with or without a study-provided Cu-IUD
- P4 ≥3.0 ng/ml
- Estimated glomerular filtration rate (eGFR) ≥90ml/min/1.73m2
- Willing to give voluntary consent and sign/mark an informed consent form
- Willing and able to comply with protocol requirements
Who cannot join
- 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.
- 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
Show all 20Show fewer
- In the last three (3) months, diagnosed with or treated for any STI or pelvic inflammatory disease
- Positive test for HIV-1, syphilis, Trichomonas vaginalis (TV), Neisseria gonorrhea (GC), Chlamydia trachomatis (CT) or HBsAg
- Nugent score greater than or equal to 7 or a symptomatic BV clinical diagnosis as defined by Amsel's criteria
- Suspected breast cancer or other progestin-sensitive cancer
- Suspected hepatic disease, including cirrhosis or viral hepatitis
- History of bleeding or coagulation problems
- Known current drug or alcohol abuse which could impact study compliance
- Grade 2 or higher laboratory abnormality, per the Division of AIDS, National Institute of Allergy and Infectious Disease (DAIDS) Table for Grading the Severity of Adverse Events, or clinically significant laboratory abnormality as determined by the clinician
- Use of any concomitant medications
- Participation in any other investigational trial with use of a drug/device within the last 30 days or planned participation in any other investigational trial with use of a drug/device during the study
- History of gynecological procedures (including genital piercing) on the external genitalia, vagina, or cervix within the last 14 days
- Labial elongation (due to pulling practices and use of botanicals or caustic agents)
- Abnormal finding on laboratory or physical examination or a social or medical condition in the volunteer which, in the opinion of the site co-PI(s), would make participation in the study unsafe or would complicate interpretation of data
- Currently using, or has used within the preceding one (1) month, emtricitabine/tenofovir disoproxil fumarate (TDF/FTC or Truvada®) or any other tenofovir product, and/or has plans to use a non-study tenofovir product in any form during the study
Trial locations and contacts
1 site in 1 country.
Kenya1 site
Kenya Medical Research Institute, Center for Global Health Research
Kisumu, Kisumu County, 40100
About this study
Official title: Phase IIa, 90-Day Safety, Adherence, and Acceptability Study of Intravaginal Rings Releasing Tenofovir With and Without Levonorgestrel Among Women in Western Kenya
The purpose of the study is to evaluate the safety, pharmacokinetics and pharmacodynamics of, and the tolerability and acceptance of an intravaginal ring (IVR) delivering both tenofovir and levonorgestrel (TFV/LNG) and an IVR delivering TFV only, compared to a placebo IVR, in women in Western Kenya.
Read the detailed description
This Phase 2a clinical trial will evaluate the safety, pharmacokinetics and pharmacodynamics of, and the tolerability and adherence to two novel intravaginal rings (IVRs). The tenofovir/levonorgestrel (TFV/LNG) IVR and TFV IVRs are designed to provide HIV (and HSV-2) prevention with and without contraceptive for pregnancy prevention, respectively. Women will be protected from pregnancy by abstinence from vaginal intercourse or agreeing to consistently use condoms; concurrent use of a non-hormonal copper intrauterine device is permitted.
The study will enroll healthy, HIV-negative, non-pregnant, menstruating women aged 18-34 years, inclusive, and not currently infected with hepatitis B virus, who are assessed to be at lower risk for HIV. The goal is to enroll fifty (50) women in Western Kenya. The participants will be randomized 2:2:1 to use one of the following continuous delivery IVRs: twenty (20) women to use the TFV/LNG IVR; ten (10) women to use the TFV IVR; and ten (10) women to use the placebo IVR. Participants will attend up to ten (10) routine study visits that may include physical and pelvic exams, collection of venous blood, vaginal fluid and cervical mucus, and behavioral questionnaires. A subset of twenty (20) women will participate in in-depth interviews.
- Conditions
- HIV, Contraception, Prevention, Anti-Retroviral Agent
- Being tested
- TFV/LNG IVR, TFV IVR, Placebo IVR
- Keywords
- Intravaginal Ring, HIV Prevention, Tenofovir, Levonorgestrel, Pregnancy Prevention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TFV/LNG IVRDrug
Also called Tenofovir/Levonorgestrel Intravaginal Ring
TFV/LNG IVR is an intravaginal ring that releases approximately 8-10 mg/day of TFV and approximately 20ug/day of LNG to be used for 90 continuous days.
TFV IVRDrug
Also called Tenofovir Intravaginal Ring
TFV IVR is an intravaginal ring that releases approximately 8-10mg/day of TFV to be used for 90 continuous days.
Placebo IVRDrug
Placebo IVR is an intravaginal ring containing no active experimental ingredients to be used for 90 continuous days.
| Study group | Role | What they receive |
|---|---|---|
| TFV/LNG IVR (10mg/20μg) (Continuous) | Experimental | Tenofovir/Levonorgestrel Intravaginal Ring Receives: Drug: TFV/LNG IVR |
| TFV IVR (10mg) (Continuous) | Experimental | Tenofovir Intravaginal Ring Receives: Drug: TFV IVR |
| Placebo IVR (Non-eluting) | Placebo comparator | Placebo Intravaginal Ring Receives: Drug: Placebo IVR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-emergent adverse events (TEAEs)
Participants with Grade 2 or higher local female genital TEAEs as defined by DAIDS Table for Grading the Severity of Adult and Pediatric AEs (version 2.1) and DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Addendum 1 Female Genital Grading Table for Use in Microbicide Studies
Measured: Change from Baseline to up to 90 days of IVR use
Safety Laboratory Assessments- Serum chemistry
Number of participants with abnormal serum chemistry
Measured: Change from Baseline to up to 90 days of IVR use
Safety Laboratory Assessments- lipids
Number of participants with abnormal lipids
Measured: Change from Baseline to up to 90 days of IVR use
Safety Laboratory Assessments- complete blood counts
Number of participants with abnormal complete blood counts
Measured: Change from Baseline to up to 90 days of IVR use
Mucosal safety
Changes in cervicovaginal mucosa by visual inspection
Measured: Change from Baseline to up to 90 days of IVR use
Secondary outcomes (17)
Maximum blood concentrations (Cmax)
Maximum plasma concentration of TFV and maximum serum concentration of LNG
Measured: Baseline; 6 and 24 hours post IVR insertion; Menstrual cycle 1, day 14; Menstrual cycle 1,day 21-25; Menstrual cycle 2, day 21-25; Menstrual cycle 3, day 14; Day 90 IVR use; 24 hours post-IVR use (anticipated cycle length is 28 days)
Maximum CV fluid concentration
Maximum CV fluid concentration of TFV
Measured: 6 and 24 hours post-IVR insertion; Menstrual cycle 1 day 14; Menstrual cycle 1 day 21-25; Menstrual cycle 2 day 21-25; Menstrual cycle 3, day 14; Day 90 of IVR use; and 24 hours post-IVR use (anticipated cycle length is 28 days)
Percent (%) inhibition of HIV resulting from product use (Anti-HIV activity)
Anti-HIV and anti-HSV-2 activity in CV fluid (inhibition in cell assay)
Measured: Baseline, Day 90 of IVR use
Percent (%) inhibition of HSV resulting from product use (Anti-HSV activity)
Anti-HSV-2 activity in CV fluid (inhibition in cell assay)
Measured: Baseline, Day 90 of IVR use
Cervical mucus assessment and quality score
Cervical mucus assessment and quality score (total summary score 0-15) as defined by WHO laboratory manual for the Examination and processing of human semen Fifth Edition, Appendix 5
Measured: Menstrual cycle 1, day 14; Menstrual cycle 3, day 14 (anticipated cycle length is 28 days)
Confirmation of Ovulation
Serum progesterone (P4) level.
Measured: Pre-IVR insertion; Menstrual cycle 1, day 20-25; Menstrual cycle 2, day 20-25; Day 90 of IVR use (anticipated cycle length is 28 days)
Cervicovaginal (CV) fluid cytokines-IL-1α
Changes in IL-1α in CV fluid.
Measured: Change from Baseline to Day 90 of IVR use
Cervicovaginal (CV) fluid cytokines- IL-8
Changes in IL-8 in CV fluid.
Measured: Change from Baseline to Day 90 of IVR use
Changes in endogenous vaginal bacteria
Changes in endogenous vaginal bacteria in CV fluid
Measured: Change from Baseline to Day 90 of IVR use
Changes in endogenous vaginal bacteria- Nugent score
Changes in Nugent score (score 0-10)
Measured: Change from Baseline to Day 90 of IVR use
qPCR of Ring Microbiota
Microbial growth on returned IVRs.
Measured: Day 90 of IVR use
Tolerability - Somatic and non-specific non-treatment emergent adverse events
Subjective and objective assessment of new complaints (e.g., headache, nausea, weight change, breast tenderness, etc.)
Measured: Baseline; 6 and 24 hours post-IVR insertion; Menstrual cycle 1, day 14; Menstrual cycle 1, day 21-25; Menstrual cycle 2, day 21-25; Menstrual cycle 3, day 14; 90 days of IVR use; 24 hours post IVR use (anticipated cycle length is 28 days)
Tolerability - Self-reported complaints of changes in menstrual cycle
Percentage of women with changes in regularity of menstrual cycle
Measured: Screening; Menstrual cycle 1, day 14; Menstrual cycle 1, day 21-25; Menstrual cycle 2, day 21-25; Menstrual cycle 3, day 14; Day 90 of IVR use; 24 hours post-IVR use (anticipated cycle length is 28 days)
Adherence - Drug concentrations
Plasma, serum, and vaginal fluid drug concentrations.
Measured: Baseline; 6 and 24 hours post-IVR insertion; Menstrual cycle 1, day 14; Menstrual cycle 1, day 21-25; Menstrual cycle 2, day 21-25; Menstrual cycle 3, day 14; 90 days of IVR use; 24 hours post-IVR use (anticipated cycle length is 28 days)
Adherence - Residual drug concentrations
Residual drug (TFV and LNG) concentrations in returned TFV/LNG and TFV IVRs and residual excipients in returned placebo IVRs.
Measured: Day 90 of IVR use
Adherence - Percentage of discontinuations
Percentage of IVR discontinuations
Measured: Up to Day 90 of IVR use
Acceptability - Quantitative assessment of acceptability based on Questionnaires administered pre- and post-IVR use
Changes in responses to questionnaires pre- and post-IVR use on attitudes toward and perspectives of IVR use.
Measured: Screening; 90 days of IVR use
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2018
- Study start12 Dec 2018
- Primary completion20 Aug 2019
- Study completionApr 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CONRAD
- Sponsor type
- University, hospital or other
- Collaborators
- Kenya Medical Research Institute, University of Washington, Centers for Disease Control and Prevention
- Responsible party
- Sponsor
- Investigators
- Nelly R. Mugo, MBChB, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03762382
- Sponsor's protocol ID
- Protocol B17-144
- Other IDs
- RFA-PS-17-005, AID-OAA-A-14-000010
- Status last verified
- Jan 2020
- First submitted
- 16 Nov 2018
- Last updated
- 14 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Data sharing will comply with CDC's current Policy on Public Health Research and Non-research Data Management and Access. Except for the analyses outlined in the study protocol, all future requests to perform new analyses on data or specimens from this study protocol will require (1) agreement of all Parties owning or jointly owning the data and (2) Ethics Committee approval.
Publications
Thurman AR, Schwartz JL, Brache V, Clark MR, McCormick T, Chandra N, Marzinke MA, Stanczyk FZ, Dezzutti CS, Hillier SL, Herold BC, Fichorova R, Asin SN, Rollenhagen C, Weiner D, Kiser P, Doncel GF. Randomized, placebo controlled phase I trial of safety, pharmacokinetics, pharmacodynamics and acceptability of tenofovir and tenofovir plus levonorgestrel vaginal rings in women. PLoS One. 2018 Jun 28;13(6):e0199778. doi: 10.1371/journal.pone.0199778. eCollection 2018.
PubMed 29953547Mugo NR, Mudhune V, Heffron R, Thomas KK, McLellan-Lemal E, Njoroge B, Peacock S, O'Connor SM, Nyagol B, Ouma E, Ridzon R, Wiener J, Isoherranen N, Erikson DW, Ouattara LA, Yousefieh N, Jacot TA, Haaland RE, Morrison SA, Haugen HS, Thurman AR, Allen SA, Baeten JM, Samandari T, Doncel GF. Randomized controlled phase IIa clinical trial of safety, pharmacokinetics and pharmacodynamics of tenofovir and tenofovir plus levonorgestrel releasing intravaginal rings used by women in Kenya. Front Reprod Health. 2023 Jun 13;5:1118030. doi: 10.3389/frph.2023.1118030. eCollection 2023.
PubMed 37383290McLellan-Lemal E, Deaton SR, Betts JE, Ondenge K, Mudhune V, O'Connor SM, Nyagol B, Thurman AR, Doncel GF, Allen SA, Heffron R, Mugo NR; Kisumu Combined Ring Study (KCRS) Team. Acceptability of an intravaginal ring for simultaneously preventing HIV infection and pregnancy: Qualitative findings of the Kisumu Combined Ring Study, 2019. Contemp Clin Trials. 2022 Nov;122:106935. doi: 10.1016/j.cct.2022.106935. Epub 2022 Sep 23.
PubMed 36162740Dabee S, Mugo N, Mudhune V, McLellan-Lemal E, Peacock S, O'Connor S, Njoroge B, Nyagol B, Thurman AR, Ouma E, Ridzon R, Wiener J, Haugen HS, Gasper M, Feng C, Allen SA, Doncel GF, Jaspan HB, Heffron R; Kisumu Combined Ring Study Team. Genital microbiota of women using a 90 day tenofovir or tenofovir and levonorgestrel intravaginal ring in a placebo controlled randomized safety trial in Kenya. Sci Rep. 2022 Jul 14;12(1):12040. doi: 10.1038/s41598-022-13475-9.
PubMed 35835755
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIa, 90-Day Safety, Adherence, and Acceptability Study of Intravaginal Rings Releasing Tenofovir With and Without Levonorgestrel Among Women in Western Kenya
- ClinicalTrials.gov ID
- NCT03762382
- Acronym / sponsor ID
- Protocol B17-144
- Conditions
- HIV, Contraception, Prevention, Anti-Retroviral Agent
- Keywords
- Intravaginal Ring, HIV Prevention, Tenofovir, Levonorgestrel, Pregnancy Prevention
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- CONRADUniversity, hospital or other
- Collaborators
- Kenya Medical Research Institute, University of Washington, Centers for Disease Control and Prevention
- Study start
- 12 Dec 2018 (actual)
- Primary completion
- 20 Aug 2019 (actual)
- Study completion
- Apr 2020 (estimated)
- First posted
- 3 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to evaluate the safety, pharmacokinetics and pharmacodynamics of, and the tolerability and acceptance of an intravaginal ring (IVR) delivering both tenofovir and levonorgestrel (TFV/LNG) and an IVR delivering TFV only, compared to a placebo IVR, in women in Western Kenya.
Detailed description
This Phase 2a clinical trial will evaluate the safety, pharmacokinetics and pharmacodynamics of, and the tolerability and adherence to two novel intravaginal rings (IVRs). The tenofovir/levonorgestrel (TFV/LNG) IVR and TFV IVRs are designed to provide HIV (and HSV-2) prevention with and without contraceptive for pregnancy prevention, respectively. Women will be protected from pregnancy by abstinence from vaginal intercourse or agreeing to consistently use condoms; concurrent use of a non-hormonal copper intrauterine device is permitted.
The study will enroll healthy, HIV-negative, non-pregnant, menstruating women aged 18-34 years, inclusive, and not currently infected with hepatitis B virus, who are assessed to be at lower risk for HIV. The goal is to enroll fifty (50) women in Western Kenya. The participants will be randomized 2:2:1 to use one of the following continuous delivery IVRs: twenty (20) women to use the TFV/LNG IVR; ten (10) women to use the TFV IVR; and ten (10) women to use the placebo IVR. Participants will attend up to ten (10) routine study visits that may include physical and pelvic exams, collection of venous blood, vaginal fluid and cervical mucus, and behavioral questionnaires. A subset of twenty (20) women will participate in in-depth interviews.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| TFV/LNG IVR (10mg/20μg) (Continuous) | Experimental | Drug: TFV/LNG IVRTenofovir/Levonorgestrel Intravaginal Ring |
| TFV IVR (10mg) (Continuous) | Experimental | Drug: TFV IVRTenofovir Intravaginal Ring |
| Placebo IVR (Non-eluting) | Placebo comparator | Drug: Placebo IVRPlacebo Intravaginal Ring |
Who may qualify
- Ages
- 18 to 34 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- 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 HIV risk score ≤4
- 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)
Key exclusion criteria (20 listed)
- 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.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TFV/LNG IVRAlso: Tenofovir/Levonorgestrel Intravaginal RingTFV/LNG IVR is an intravaginal ring that releases approximately 8-10 mg/day of TFV and approximately 20ug/day of LNG to be used for 90 continuous days. | Drug | TFV/LNG IVR (10mg/20μg) (Continuous) |
| TFV IVRAlso: Tenofovir Intravaginal RingTFV IVR is an intravaginal ring that releases approximately 8-10mg/day of TFV to be used for 90 continuous days. | Drug | TFV IVR (10mg) (Continuous) |
| Placebo IVRPlacebo IVR is an intravaginal ring containing no active experimental ingredients to be used for 90 continuous days. | Drug | Placebo IVR (Non-eluting) |
Primary outcome
Treatment-emergent adverse events (TEAEs)
Time frame: Change from Baseline to up to 90 days of IVR use
Participants with Grade 2 or higher local female genital TEAEs as defined by DAIDS Table for Grading the Severity of Adult and Pediatric AEs (version 2.1) and DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Addendum 1 Female Genital Grading Table for Use in Microbicide Studies
Safety Laboratory Assessments- Serum chemistry
Time frame: Change from Baseline to up to 90 days of IVR use
Number of participants with abnormal serum chemistry
Safety Laboratory Assessments- lipids
Time frame: Change from Baseline to up to 90 days of IVR use
Number of participants with abnormal lipids
Safety Laboratory Assessments- complete blood counts
Time frame: Change from Baseline to up to 90 days of IVR use
Number of participants with abnormal complete blood counts
Mucosal safety
Time frame: Change from Baseline to up to 90 days of IVR use
Changes in cervicovaginal mucosa by visual inspection
17 secondary outcomes
Maximum blood concentrations (Cmax)
Time frame: Baseline; 6 and 24 hours post IVR insertion; Menstrual cycle 1, day 14; Menstrual cycle 1,day 21-25; Menstrual cycle 2, day 21-25; Menstrual cycle 3, day 14; Day 90 IVR use; 24 hours post-IVR use (anticipated cycle length is 28 days)
Maximum CV fluid concentration
Time frame: 6 and 24 hours post-IVR insertion; Menstrual cycle 1 day 14; Menstrual cycle 1 day 21-25; Menstrual cycle 2 day 21-25; Menstrual cycle 3, day 14; Day 90 of IVR use; and 24 hours post-IVR use (anticipated cycle length is 28 days)
Percent (%) inhibition of HIV resulting from product use (Anti-HIV activity)
Time frame: Baseline, Day 90 of IVR use
Percent (%) inhibition of HSV resulting from product use (Anti-HSV activity)
Time frame: Baseline, Day 90 of IVR use
Cervical mucus assessment and quality score
Time frame: Menstrual cycle 1, day 14; Menstrual cycle 3, day 14 (anticipated cycle length is 28 days)
Confirmation of Ovulation
Time frame: Pre-IVR insertion; Menstrual cycle 1, day 20-25; Menstrual cycle 2, day 20-25; Day 90 of IVR use (anticipated cycle length is 28 days)
Cervicovaginal (CV) fluid cytokines-IL-1α
Time frame: Change from Baseline to Day 90 of IVR use
Cervicovaginal (CV) fluid cytokines- IL-8
Time frame: Change from Baseline to Day 90 of IVR use
Changes in endogenous vaginal bacteria
Time frame: Change from Baseline to Day 90 of IVR use
Changes in endogenous vaginal bacteria- Nugent score
Time frame: Change from Baseline to Day 90 of IVR use
qPCR of Ring Microbiota
Time frame: Day 90 of IVR use
Tolerability - Somatic and non-specific non-treatment emergent adverse events
Time frame: Baseline; 6 and 24 hours post-IVR insertion; Menstrual cycle 1, day 14; Menstrual cycle 1, day 21-25; Menstrual cycle 2, day 21-25; Menstrual cycle 3, day 14; 90 days of IVR use; 24 hours post IVR use (anticipated cycle length is 28 days)
Tolerability - Self-reported complaints of changes in menstrual cycle
Time frame: Screening; Menstrual cycle 1, day 14; Menstrual cycle 1, day 21-25; Menstrual cycle 2, day 21-25; Menstrual cycle 3, day 14; Day 90 of IVR use; 24 hours post-IVR use (anticipated cycle length is 28 days)
Adherence - Drug concentrations
Time frame: Baseline; 6 and 24 hours post-IVR insertion; Menstrual cycle 1, day 14; Menstrual cycle 1, day 21-25; Menstrual cycle 2, day 21-25; Menstrual cycle 3, day 14; 90 days of IVR use; 24 hours post-IVR use (anticipated cycle length is 28 days)
Adherence - Residual drug concentrations
Time frame: Day 90 of IVR use
Adherence - Percentage of discontinuations
Time frame: Up to Day 90 of IVR use
Acceptability - Quantitative assessment of acceptability based on Questionnaires administered pre- and post-IVR use
Time frame: Screening; 90 days of IVR use
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2020.
- Background: PubMed 29953547Thurman AR, Schwartz JL, Brache V, Clark MR, McCormick T, Chandra N, Marzinke MA, Stanczyk FZ, Dezzutti CS, Hillier SL, Herold BC, Fichorova R, Asin SN, Rollenhagen C, Weiner D, Kiser P, Doncel GF. Randomized, placebo controlled phase I trial of safety, pharmacokinetics, pharmacodynamics and acceptability of tenofovir and tenofovir plus levonorgestrel vaginal rings in women. PLoS One. 2018 Jun 28;13(6):e0199778. doi: 10.1371/journal.pone.0199778. eCollection 2018.
- Derived from this study: PubMed 37383290Mugo NR, Mudhune V, Heffron R, Thomas KK, McLellan-Lemal E, Njoroge B, Peacock S, O'Connor SM, Nyagol B, Ouma E, Ridzon R, Wiener J, Isoherranen N, Erikson DW, Ouattara LA, Yousefieh N, Jacot TA, Haaland RE, Morrison SA, Haugen HS, Thurman AR, Allen SA, Baeten JM, Samandari T, Doncel GF. Randomized controlled phase IIa clinical trial of safety, pharmacokinetics and pharmacodynamics of tenofovir and tenofovir plus levonorgestrel releasing intravaginal rings used by women in Kenya. Front Reprod Health. 2023 Jun 13;5:1118030. doi: 10.3389/frph.2023.1118030. eCollection 2023.
- Derived from this study: PubMed 36162740McLellan-Lemal E, Deaton SR, Betts JE, Ondenge K, Mudhune V, O'Connor SM, Nyagol B, Thurman AR, Doncel GF, Allen SA, Heffron R, Mugo NR; Kisumu Combined Ring Study (KCRS) Team. Acceptability of an intravaginal ring for simultaneously preventing HIV infection and pregnancy: Qualitative findings of the Kisumu Combined Ring Study, 2019. Contemp Clin Trials. 2022 Nov;122:106935. doi: 10.1016/j.cct.2022.106935. Epub 2022 Sep 23.
- Derived from this study: PubMed 35835755Dabee S, Mugo N, Mudhune V, McLellan-Lemal E, Peacock S, O'Connor S, Njoroge B, Nyagol B, Thurman AR, Ouma E, Ridzon R, Wiener J, Haugen HS, Gasper M, Feng C, Allen SA, Doncel GF, Jaspan HB, Heffron R; Kisumu Combined Ring Study Team. Genital microbiota of women using a 90 day tenofovir or tenofovir and levonorgestrel intravaginal ring in a placebo controlled randomized safety trial in Kenya. Sci Rep. 2022 Jul 14;12(1):12040. doi: 10.1038/s41598-022-13475-9.
- Individual participant dataSharing planned: No. Data sharing will comply with CDC's current Policy on Public Health Research and Non-research Data Management and Access. Except for the analyses outlined in the study protocol, all future requests to perform new analyses on data or specimens from this study protocol will require (1) agreement of all Parties owning or jointly owning the data and (2) Ethics Committee approval.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nelly R. Mugo, MBChB principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TFV/LNG IVR and TFV IVR in people with HIV and Contraception, run by CONRAD at 1 site in Kenya.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-emergent adverse events (TEAEs) (time frame: Change from Baseline to up to 90 days of IVR use). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03762382, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2020.