Effect of Tenofovir on Genital Herpes Simplex Virus (HSV) Shedding

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
CONRAD
Gilead Sciences
Information provided by (Responsible Party):
Anna Wald, University of Washington
ClinicalTrials.gov Identifier:
NCT01448616
First received: September 14, 2011
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

The investigators propose a randomized, double blind, placebo-controlled, cross-over trial to evaluate the effect of oral and topical (vaginal gel) tenofovir on genital herpes simplex virus (HSV) shedding among herpes simplex virus type-2 (HSV-2) seropositive, human immunodeficiency virus (HIV) seronegative women. The investigators hypothesize that tenofovir will reduce genital HSV shedding compared to placebo.


Condition Intervention Phase
Herpes Simplex Type II
Drug: Tenofovir
Drug: placebo gel
Drug: tenofovir disoproxil fumarate (TDF)
Drug: placebo tablets
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Tenofovir on Genital HSV Shedding: a Randomized, Double-blind, Placebo-controlled Clinical Trial

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • HSV shedding [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    The within-person changes in rate of HSV shedding during tenofovir administration arm compared with the rate of HSV shedding during placebo administration


Secondary Outcome Measures:
  • within-person changes in copy numbers of HSV [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    The within-person changes in copy numbers of HSV during tenofovir administration compared with placebo on the days that shedding is observed

  • Average copy numbers of HSV [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    The average copy over all days including days with no detection

  • Lesion rate [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    The rate of days with lesions during tenofovir administration compared with placebo

  • Shedding on no lesion days [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    The rate of HSV shedding on days without lesions

  • Number of participants with adverse events (AEs) as a measure of safety and tolerability. [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]
    Nature, frequency, duration, severity and causality of adverse events (AEs)


Estimated Enrollment: 55
Study Start Date: February 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Run-in Phase
Women will first participate in a run-in phase with twice daily swabbing.
Experimental: Study Drug Phase
Participants will be randomized 2:2:1 to one of three groups: 1) oral tenofovir and placebo gel, 2) oral placebo and tenofovir gel, or 3) oral placebo and placebo gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drug will be administered daily.
Drug: Tenofovir
Tenofovir 1% gel (w/w) is a gel formulation of tenofovir. Study participants are instructed to insert one dose (the entire contents of one applicator) of product into the vagina once each day. They are instructed to insert their gel as close to the same time each day as possible.
Drug: placebo gel

Study participants are instructed to insert one dose (the entire contents of one applicator) of product into the vagina once each day. They are instructed to insert their gel as close to the same time each day as possible.

The placebo gel (known as the 'universal' placebo gel) is formulated to minimize any possible effects — negative or positive — on study endpoints.

Drug: tenofovir disoproxil fumarate (TDF)
Oral tenofovir will be administered as tablets. TDF (Viread®) tablets contain 300 mg of tenofovir disoproxil fumarate, which is equivalent to 245 mg of tenofovir disoproxil. Study participants are instructed to take the one tablet, by mouth, once each day without regard to meals.
Drug: placebo tablets
TDF placebo tablets are film-coated and contain denatonium benzoate, a bittering agent, in addition to other inactive ingredients. Study participants are instructed to take the one tablet, by mouth, once each day without regard to meals.

Detailed Description:

The investigators propose a randomized, double-blind, placebo-controlled, cross-over study of 55 adult, healthy women who are HSV-2 seropositive and HIV-1 seronegative. Women will first participate in a run-in phase with twice daily swabbing. Following 4 weeks of swabbing, participants will be randomized 2:2:1 to one of three groups: 1) oral tenofovir and placebo gel, 2) oral placebo and tenofovir gel, or 3) oral placebo and placebo gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drug will be administered daily.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women age 18-50
  • HSV-2 seropositive by the University of Washington (UW) Western blot
  • History of recurrent genital herpes, with more than 4 recurrences but less than 10 in the last year or, if currently on suppressive therapy, with more than 4 recurrences but less than 10 in the year prior to starting suppressive therapy
  • HIV negative
  • General good health
  • Willing to not use antiviral therapy (other than the study drug) for the duration of the study
  • Willing to obtain a swab from genital secretions twice daily for the duration of the study
  • Willing to use effective birth control
  • Able to provide written informed consent at screening and enrollment

Exclusion Criteria:

  • HIV positive or at high risk for HIV acquisition (intravenous drug user or HIV+ sex partner)
  • Hepatitis B (HepB) antigen (Ag) positive, or at high risk for HepB acquisition and not vaccinated
  • Have a history of adverse reaction to tenofovir and/or adefovir
  • Immunosuppressive medications, except for intranasal or topical (not high potency) steroids.
  • Any kidney disease, or renal insufficiency, defined as serum creatinine >1.5 mg/dl. Participants with a prior history of a single episode of pyelonephritis will be eligible.
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times upper limit of normal
  • Pregnancy, as confirmed by a urine pregnancy test, planning to become pregnant during the course of the trial, or breast-feeding.
  • Serious medical conditions or active infections
  • Any other conditions that in the judgment of the investigator would preclude successful completion of the clinical trial.
  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: NCT01448616

Locations
United States, Washington
University of Washington Virology Research Clinic
Seattle, Washington, United States, 98104
Sponsors and Collaborators
University of Washington
CONRAD
Gilead Sciences
Investigators
Principal Investigator: Anna Wald, MD, MPH University of Washington
  More Information

No publications provided

Responsible Party: Anna Wald, Professor, University of Washington
ClinicalTrials.gov Identifier: NCT01448616     History of Changes
Other Study ID Numbers: 41250-A
Study First Received: September 14, 2011
Last Updated: June 3, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Herpes Simplex
DNA Virus Infections
Herpesviridae Infections
Skin Diseases
Skin Diseases, Infectious
Skin Diseases, Viral
Virus Diseases
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014