Effect of Tenofovir on Genital Herpes Simplex Virus (HSV) Shedding - Full Text View

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:

MedlinePlus related topics: Genital Herpes Herpes Simplex

Drug Information available for: Formic acid Tenofovir Tenofovir Disoproxil Fumarate

U.S. FDA Resources

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:	December 2013
Estimated Primary Completion Date:	December 2013 (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.

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01448616

Contacts

Contact: Virology Research Clinic

(206) 520-4340

Locations

United States, Washington
University of Washington Virology Research Clinic	Recruiting
Seattle, Washington, United States, 98104
Contact: Virology Research Clinic 206-520-4340
Principal Investigator: Anna Wald, MD, MPH

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, Principal Investigator, University of Washington
ClinicalTrials.gov Identifier:	NCT01448616 History of Changes
Other Study ID Numbers:	41250-A
Study First Received:	September 14, 2011
Last Updated:	March 12, 2013
Health Authority:	United States: Institutional Review Board United States: Food and Drug Administration

Additional relevant MeSH terms:

Herpes Genitalis
Herpes Simplex
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Genital Diseases, Male
Genital Diseases, Female
Skin Diseases, Viral
Skin Diseases, Infectious
Skin Diseases

Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on May 22, 2013