Safety and Pharmacokinetic Study of HIV Prophylaxis Using Antiretroviral Intravaginal Rings in Healthy Women

NCT ID: NCT02431273

Last Updated: 2019-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2016-12-31

Brief Summary

This study will evaluate the hypothesis that intravaginal rings (IVRs) can safely and in a sustained fashion, deliver the antiretroviral (ARV) drugs - tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and maraviroc (MVC), in healthy women when used in the following drug combinations: 1) TDF ("Single" IVR); 2) TDF-FTC ("Dual" IVR) and; 3) TDF-FTC-MVC ("Triple" IVR).

TDF = tenofovir disoproxil fumarate; FTC = emtrcitabine; MVC = maraviroc

Detailed Description

The broad long term goal of this project is to empower women to protect themselves from HIV through woman-controlled sustained local delivery of ARTs via intravaginal rings. The short-term general investigational plan is to evaluate IVRs releasing TDF, TDF-FTC and TDF-FTC-MVC in healthy women for up to 7 days in an open-label study to determine safety and drug concentrations in plasma and cervicovaginal lavage and secretions. Additional exploratory studies will be considered and planned based in part on the results obtained in this study. The long-term investigational plan is to evaluate the safety and efficacy of sustained release TDF, TDF-FTC and TDF-FTC-MVC for their ability to decrease HIV transmission to vulnerable women.

Conditions

Human Immunodeficiency Virus (HIV) Prophylaxis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

TDF (Single IVR)

All subjects will be asked to wear "Single" (TDF) IVRs for 7 days.

Group Type: EXPERIMENTAL

TDF IVR

Intervention Type: DRUG

TDF-FTC (Dual IVR)

If the TDF IVR is determined as safe, study participants will be asked to replace it with "Dual" (TDF-FTC) IVRs for 7 days. There will be follow-up visit between removal of a single IVR and replacing it with a dual IVR.

Group Type: EXPERIMENTAL

TDF-FTC IVR

Intervention Type: DRUG

TDF-FTC-MVC (Triple IVR)

If the TDF-FTC IVR is determined as safe, study participants will be asked to replace them with "Triple" (TDF-FTC-MVC) IVRs for 7 days. There will be follow-up visit between removal of a dual IVR and replacing it with a triple IVR.

Group Type: EXPERIMENTAL

TDF-FTC-MVC IVR

Intervention Type: DRUG

Interventions

TDF IVR

Intervention Type: DRUG

TDF-FTC IVR

Intervention Type: DRUG

TDF-FTC-MVC IVR

Intervention Type: DRUG

Other Intervention Names

Single IVR; Dual IVR; Triple IVR

Eligibility Criteria

Inclusion Criteria

• Provides written informed consent
• Healthy female 18-45 years of age
• HIV negative per subject report and results of screening examination
• Negative for sexually transmitted diseases in the past 3 months and at screening exam
• No history of genital herpes simplex I or II per subject report
• Currently using contraception with plans to continue throughout the study duration or having sex with females only
• Pre-menopausal with a regular menstrual cycle with at least 21 days between menses and no history of intermenstrual bleeding or with suppressed menstrual cycle by hormonal contraception such as Depo-Provera or continuous oral contraceptive agents
• Subjects must agree to abstain from vaginal, anal, and oral sex throughout the first week of each dosing period and then use condoms for vaginal/rectal intercourse until after the final visit for use of each IVR
• Subjects must agree to not douche or use any vaginal product other than the Single, Dual and Triple ARV IVRs, including lubricants, feminine hygiene products, and vaginal drying agents throughout the dosing period and until after the final visit
• Subjects must agree to blood draws and vaginal exams throughout the course of the study

Exclusion Criteria

• HIV positive by subject report or results of screening examination
• Positive history for autoimmune disease
• Abnormal genital exam defined as grade 1 or higher adverse event by DAIDS genital AE grading table
• Abnormal ALT or AST or Hepatitis B infection
• Active vaginal infection as determined by site IoR
• Abnormal renal function (defined as a creatinine clearance of <50mL/min/1.73 m2)
• Pregnant or less than 6 months post-partum or current lactation
• Current use of an IVR (i.e., Nuvaring, Estring, Femring)
• History of TDF, FTC, and MVC use and/or adverse reaction to any of these drugs
• History of adverse reaction to silicone
• History of toxic shock syndrome
• Currently receiving chemotherapy or immunosuppressive agents
• Use of investigative drugs within 30 days or 5 half-lives
• Currently using or suspected to be using non-therapeutic injection drugs

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

The University of Texas Medical Branch, Galveston

OTHER

Sponsor Role: collaborator

Oak Crest Institute of Science

OTHER

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Auritec Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kathleen L Vincent, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Medical Branch (UTMB)

Locations

University of Texas Medical Branch

Galveston, Texas, United States

Countries

United States

References

Vincent KL, Moss JA, Marzinke MA, Hendrix CW, Anton PA, Pyles RB, Guthrie KM, Dawson L, Olive TJ, Butkyavichene I, Churchman SA, Cortez JM Jr, Fanter R, Gunawardana M, Miller CS, Yang F, Rosen RK, Vargas SE, Baum MM. Safety and pharmacokinetics of single, dual, and triple antiretroviral drug formulations delivered by pod-intravaginal rings designed for HIV-1 prevention: A Phase I trial. PLoS Med. 2018 Sep 28;15(9):e1002655. doi: 10.1371/journal.pmed.1002655. eCollection 2018 Sep.

Reference Type: DERIVED

PMID: 30265679 (View on PubMed)

Moss JA, Butkyavichene I, Churchman SA, Gunawardana M, Fanter R, Miller CS, Yang F, Easley JT, Marzinke MA, Hendrix CW, Smith TJ, Baum MM. Combination Pod-Intravaginal Ring Delivers Antiretroviral Agents for HIV Prophylaxis: Pharmacokinetic Evaluation in an Ovine Model. Antimicrob Agents Chemother. 2016 May 23;60(6):3759-66. doi: 10.1128/AAC.00391-16. Print 2016 Jun.

Reference Type: DERIVED

PMID: 27067321 (View on PubMed)

Other Identifiers

2R44HD075636-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ARV-IVR 01

Identifier Type: -

Identifier Source: org_study_id