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

Herpes Simplex Type II Clinical Trial

Official title:

Effect of Tenofovir on Genital HSV Shedding: a Randomized, Double-blind, Placebo-controlled Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01448616
• Other study ID #: 41250
• Status: Completed
• Phase: Phase 4
• Start date: February 2012
• Est. completion date: June 2015

Study information

• Verified date: February 2023
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Herpes Simplex
• Herpes Simplex Type II

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	University of Washington Virology Research Clinic	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
University of Washington	CONRAD, Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HSV Shedding Rate in Those Receiving Oral TDF, Vaginal TFV, or Double Placebo	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.	Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase
Secondary	Within-person Changes in Log-copy Numbers of HSV	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.	Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase
Secondary	Genital Lesion Rate	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.	Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase
Secondary	Asymptomatic Shedding (Shedding on Days Without Genital Lesions)	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.	Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase