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

This study has been completed.

Sponsor:

Collaborators:

The University of Texas Medical Branch, Galveston

Oak Crest Institute of Science

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

Information provided by (Responsible Party):

Auritec Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT02431273

First received: August 4, 2014

Last updated: January 31, 2017

Last verified: January 2017

History of Changes

Purpose

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).

Condition	Intervention	Phase
Human Immunodeficiency Virus (HIV) Prophylaxis	Drug: TDF IVR Drug: TDF-FTC IVR Drug: TDF-FTC-MVC IVR	Early Phase 1


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: No masking Primary Purpose: Prevention
Official Title:	Open-Label Safety and Pharmacokinetic Study of Single (TDF), Dual (TDF-FTC), and Triple ARV IVR (TDF-FTC-MVC) in Healthy Women

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Further study details as provided by Auritec Pharmaceuticals:

Primary Outcome Measures:

Safety of the Single, Dual and Triple ARV IVRs. [ Time Frame: Days 0-21 following insertion of each IVR. ]
Number of Participants with Adverse Events (AEs) will be recorded. Safety parameters that will be monitored for each IVR combination and the grading scale for each parameter will follow the Female Genital Grading Table for Use in Microbicide Studies. AEs not included in that table will be graded using the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014.
Pharmacokinetics of the Single, Dual and Triple ARV IVRs. [ Time Frame: Days 0-21 following insertion of each IVR. ]
Drug concentrations in plasma and cervicovaginal fluids will be evaluated for each IVR combination.

Secondary Outcome Measures:

Acceptability of the IVRs. [ Time Frame: Days 0-21 following insertion of each IVR. ]
Acceptability and comfort will be assessed.


Enrollment:	6
Actual Study Start Date:	June 2015
Study Completion Date:	December 2016
Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: TDF (Single IVR) All subjects will be asked to wear "Single" (TDF) IVRs for 7 days.	Drug: TDF IVR Other Name: Single IVR
Experimental: 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.	Drug: TDF-FTC IVR Other Name: Dual IVR
Experimental: 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.	Drug: TDF-FTC-MVC IVR Other Name: Triple IVR

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.

Eligibility


Ages Eligible for Study:	18 Years to 45 Years (Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02431273

Locations


United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77555-0587

Sponsors and Collaborators

Auritec Pharmaceuticals

The University of Texas Medical Branch, Galveston

Oak Crest Institute of Science

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

Investigators


Principal Investigator:	Kathleen L Vincent, MD	University of Texas Medical Branch (UTMB)

More Information


Responsible Party:	Auritec Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT02431273 History of Changes
Other Study ID Numbers:	ARV-IVR 01 2R44HD075636-02 ( U.S. NIH Grant/Contract )
Study First Received:	August 4, 2014
Last Updated:	January 31, 2017

Keywords provided by Auritec Pharmaceuticals:


TDF FTC MVC TDF-FTC	TDF-FTC-MVC IVR ARV

Additional relevant MeSH terms:


Immunologic Deficiency Syndromes Acquired Immunodeficiency Syndrome HIV Infections Immune System Diseases Lentivirus Infections Retroviridae Infections	RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases

ClinicalTrials.gov processed this record on July 14, 2017

To Top