Clinical Trials

MainTitle

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

This study has been completed
Sponsor
Auritec Pharmaceuticals

Collaborator
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: June 25, 2019
Last Verified: June 2019
History of Changes
Purpose

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).

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

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: None (Open Label)
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

Further study details as provided by Auritec Pharmaceuticals:

Primary Outcome Measures

  • Number of Participants With Specific Graded Adverse Events in Single, Dual, and Triple Antiretroviral (ARV) Intravaginal Rings (IVRs) [ Time Frame: Days 0-21 following insertion of each IVR. ]
    Number of Adverse Events (AEs) was recorded. Safety parameters were monitored for each IVR combination and the grading scale for each parameter followed the Female Genital Grading Table for Use in Microbicide Studies. AEs not included in that table were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014 (Grade 1 = mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Potentially Life-Threatening).
  • Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Fluid (CVF) [ Time Frame: Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal). ]
    Drug concentrations [tenofovir (TFV), tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)] in cervicovaginal fluids (CVF) for each IVR combination.
  • Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Cervicovaginal Lavage (CVL) [ Time Frame: Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal). ]
    Drug concentrations [tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)] in cervicovaginal lavage (CVL) were evaluated for each IVR combination.
  • Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Vaginal Tissue [ Time Frame: Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal). ]
    Drug concentrations [tenofovir disoproxil fumarate (TDF), tenofovir (TFV), tenofovir diphosphate (TFV-DP), emtricitabine (FTC) and maraviroc (MVC)] in vaginal tissue (VT) were evaluated for each IVR combination.
  • Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Plasma [ Time Frame: Time points at which outcome measure was assessed are Days 2 (after IVR insertion) and 7 (day of IVR removal). ]
    Drug concentrations [tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)] in plasma were evaluated for each IVR combination.
  • Pharmacokinetics of the Single, Dual and Triple ARV IVRs: Terminal Half-life [ Time Frame: Time points at which outcome measure was assessed are Day 7 (day of IVR removal) and daily up to 14 days. ]
    Drug concentrations [tenofovir disoproxil fumarate (TDF), emtricitabine (FTC) and maraviroc (MVC)] in terminal half-life were evaluated for each IVR combination.
Secondary Outcome Measures:
  • Acceptability of the IVRs [ Time Frame: Days 0-21 following insertion of each IVR. ]
    Acceptability of the IVRs was assessed through reported willingness to use the IVR for 28 days in a real-world setting on a likert scale, 1 being "not at all confident" to 5 being "completely confident" for Periods 1 and 2.

Enrollment: 10
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

Eligibility

Ages Eligible for Study: 18 Years to 45 Years  
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

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

More Information


Responsible Party: Auritec Pharmaceuticals  
ClinicalTrials.gov Identifier: NCT02431273   History of Changes  
Other Study ID Numbers: ARV-IVR 01  
  2R44HD075636-02  
Study First Received: August 4, 2014  
Last Updated: June 25, 2019  

Keywords provided by Auritec Pharmaceuticals:

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

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections

ClinicalTrials.gov processed this data on June 02, 2020
This information is provided by ClinicalTrials.gov.