Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
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: December 2, 2015
Last verified: December 2015
  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: TDF
Drug: Placebo Vaginal Gel
Drug: Vaginal TFV Gel
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 Rate in Those Receiving Oral TDF, Vaginal TFV, or Double Placebo [ Time Frame: Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase ] [ Designated as safety issue: No ]
    The within-person changes in rate of HSV shedding during study drug administration (treatment phase) compared with the rate of HSV shedding during lead-in observation phase in the same participants. We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment. This is analyzed separately for each treatment arm and not compared between arms.


Secondary Outcome Measures:
  • Within-person Changes in Log-copy Numbers of HSV [ Time Frame: Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase ] [ Designated as safety issue: No ]

    The within-person changes in mean log-copy numbers of HSV shed during treatment phase (oral TDF, vaginal TFV, or double placebo) compared with the lead-in (observation) phase in the same participants. Each treatment arm is analyzed separately without comparison between arms.

    We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment.


  • Genital Lesion Rate [ Time Frame: Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase ] [ Designated as safety issue: No ]

    The within person change in proportion of days with lesions between the lead-in (observational) and study drug (treatment) phase for each arm separately. No between arm comparisons were performed. We include intent to treat with all randomized participants as well as per protocol (persons receiving study drug for at least 30 days with 90% or better reported compliance per returned product counts).

    We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment.


  • Asymptomatic Shedding (Shedding on Days Without Genital Lesions) [ Time Frame: Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase ] [ Designated as safety issue: No ]

    Within person changes in shedding on days without lesions between the lead-in (observational) phase and the study drug (treatment) phase. Each arm is evaluated separately and no inter arm comparisons are made.

    We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment.



Enrollment: 73
Study Start Date: February 2012
Study Completion Date: June 2015
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: TDF
Participants will take tenofovir disoproxil fumarate (TDF) tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
Drug: 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.
Other Name: Tenofovir disoproxil fumarate (TDF) oral tablets
Drug: Placebo Vaginal 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.

Other Name: Placebo gel
Experimental: Study Drug Phase: Vaginal TFV Gel
Participants will take oral placebo tablets and apply a tenofovir 1% (TFV) vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
Drug: Vaginal TFV Gel
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.
Other Name: Tenofovir 1% Vaginal Gel
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.
Other Name: Oral placebo
Placebo Comparator: Study Drug Phase: Double Placebo
Participants will take oral placebo tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
Drug: Placebo Vaginal 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.

Other Name: Placebo gel
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.
Other Name: Oral placebo

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   (Adult)
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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Anna Wald, Professor, University of Washington
ClinicalTrials.gov Identifier: NCT01448616     History of Changes
Other Study ID Numbers: 41250-J 
Study First Received: September 14, 2011
Results First Received: August 5, 2015
Last Updated: December 2, 2015
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 28, 2016