Tenofovir/Levonorgestrel Intravaginal Ring and Tenofovir Intravaginal Ring

NCT03762382 | Unknown Phase 2 FDA Drug

• 3 other identifiers: Protocol B17-144RFA-PS-17-005AID-OAA-A-14-000010
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV; Contraception; Prevention; Anti-Retroviral Agent

Keywords

Intravaginal Ring; HIV Prevention; Tenofovir; Levonorgestrel; Pregnancy Prevention

Outcome Measures

Primary Outcomes (5)

• 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

  Change from Baseline to up to 90 days of IVR use

• Safety Laboratory Assessments- Serum chemistry

  Number of participants with abnormal serum chemistry

  Change from Baseline to up to 90 days of IVR use

• Safety Laboratory Assessments- lipids

  Number of participants with abnormal lipids

  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

  Change from Baseline to up to 90 days of IVR use

• Mucosal safety

  Changes in cervicovaginal mucosa by visual inspection

  Change from Baseline to up to 90 days of IVR use

Secondary Outcomes (17)

• Maximum blood concentrations (Cmax)

  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

  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)

  Baseline, Day 90 of IVR use

• Percent (%) inhibition of HSV resulting from product use (Anti-HSV activity)

  Baseline, Day 90 of IVR use

• Cervical mucus assessment and quality score

  Menstrual cycle 1, day 14; Menstrual cycle 3, day 14 (anticipated cycle length is 28 days)

Other Outcomes (1)

• Qualitative assessment of acceptability and adherence influences through In-depth interviews

  Between Menstrual cycle 2, day 21-25 and Menstrual cycle 3, day 14 (anticipated cycle length is 28 days)

Study Arms (3)

TFV/LNG IVR (10mg/20μg) (Continuous)

EXPERIMENTAL

Tenofovir/Levonorgestrel Intravaginal Ring

Drug: TFV/LNG IVR

TFV IVR (10mg) (Continuous)

EXPERIMENTAL

Tenofovir Intravaginal Ring

Drug: TFV IVR

Placebo IVR (Non-eluting)

PLACEBO COMPARATOR

Placebo Intravaginal Ring

Drug: Placebo IVR

Interventions

TFV/LNG IVR DRUG

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.

Also known as: Tenofovir/Levonorgestrel Intravaginal Ring

TFV/LNG IVR (10mg/20μg) (Continuous)

TFV IVR DRUG

TFV IVR is an intravaginal ring that releases approximately 8-10mg/day of TFV to be used for 90 continuous days.

Also known as: Tenofovir Intravaginal Ring

TFV IVR (10mg) (Continuous)

Placebo IVR DRUG

Placebo IVR is an intravaginal ring containing no active experimental ingredients to be used for 90 continuous days.

Placebo IVR (Non-eluting)

Eligibility Criteria

• Age: 18 Years - 34 Years
• Gender Eligibility Details: Healthy, non-pregnant females of reproductive potential, ovulating and not using non-study hormonal contraception during the study period.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• CONRAD: lead
• Kenya Medical Research Institute: collaborator
• University of Washington: collaborator
• Centers for Disease Control and Prevention: collaborator

Study Sites (1)

Kenya Medical Research Institute, Center for Global Health Research

Kisumu, Kisumu County, 40100, Kenya

Location

Related Publications (4)

• 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.

  PMID: 29953547 BACKGROUND

• Mugo 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.

  PMID: 37383290 DERIVED

• McLellan-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.

  PMID: 36162740 DERIVED

• Dabee 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.

  PMID: 35835755 DERIVED

MeSH Terms

Interventions

Tenofovir

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Nelly R. Mugo, MBChB

  University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: December 3, 2018
• Study Start: December 12, 2018
• Primary Completion: August 20, 2019
• Study Completion: April 1, 2020
• Last Updated: January 14, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

KE (1)