Overview

This trial is active, not recruiting.

Condition hiv-1 infection
Treatments ftc/tdf, f/taf, allowed third antiretroviral agent, placebo to match ftc/tdf, placebo to match f/taf
Phase phase 3
Sponsor Gilead Sciences
Start date May 2014
End date August 2015
Trial size 665 participants
Trial identifier NCT02121795, 2013-005138-39, GS-US-311-1089

Summary

This study will evaluate the efficacy and safety of switching from emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) fixed dose combination (FDC) to emtricitabine/tenofovir alafenamide (F/TAF) FDC versus maintaining a treatment regimen of FTC/TDF FDC in HIV-1 positive participants who are virologically suppressed on regimens containing FTC/TDF. Efficacy will be determined by the proportion of participants with HIV-1 RNA < 50 copies/mL at Week 48.

This study will consist of a 96 week double-blind treatment period. After Week 96, all participants will continue on blinded study drug treatment and attend visits every 12 weeks until treatment assignments are unblinded. All participants will return for an unblinding visit and will be given the option to receive open-label F/TAF and attend visits every 12 weeks until F/TAF is commercially available, or the sponsor terminates the F/TAF clinical development program.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Participants will receive emtricitabine 200 mg/tenofovir alafenamide 10 mg or 25 mg (F/TAF) plus placebo to match FTC/TDF, while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks. Dosing of F/TAF will be dependent on the third agent of the participants' pre-existing treatment regimen.
f/taf
F/TAF FDC tablet administered orally once daily
allowed third antiretroviral agent
An allowed third antiretroviral agent of the participant's pre-existing regimen may include one of the following: ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, ritonavir-boosted darunavir, efavirenz (as individual agent only), rilpivirine (as individual agent only), nevirapine, raltegravir, dolutegravir, and maraviroc.
placebo to match ftc/tdf
Placebo to match FTC/TDF FDC tablets administered orally once daily
(Active Comparator)
Participants will receive emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg (FTC/TDF) plus placebo to match F/TAF, while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks.
ftc/tdf Truvada®
FTC/TDF FDC tablets administered orally once daily
allowed third antiretroviral agent
An allowed third antiretroviral agent of the participant's pre-existing regimen may include one of the following: ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, ritonavir-boosted darunavir, efavirenz (as individual agent only), rilpivirine (as individual agent only), nevirapine, raltegravir, dolutegravir, and maraviroc.
placebo to match f/taf
Placebo to match F/TAF FDC tablets administered orally once daily

Primary Outcomes

Measure
Proportion of participants with HIV-1 RNA < 50 copies/mL as defined by the FDA snapshot analysis
time frame: Week 48

Secondary Outcomes

Measure
Percent change from baseline in hip bone mineral density (BMD)
time frame: Baseline to Week 48
Percent change from baseline in spine BMD
time frame: Baseline to Week 48
Proportion of participants with HIV-1 RNA < 50 copies/mL as defined by the FDA snapshot analysis
time frame: Week 96
Proportion of participants with HIV-1 RNA < 20 copies/mL as defined by the FDA snapshot analysis
time frame: Weeks 48 and 96
Change from baseline in CD4+ cell count
time frame: Baseline to Weeks 48 and 96
Percent change from baseline in hip and spine BMD
time frame: Baseline to Week 96

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures - Currently receiving antiretroviral regimen containing FTC/TDF in combination with one third agent for ≥ 6 consecutive months prior to screening. - Plasma HIV-1 RNA levels < 50 copies/mL for at least 6 months preceding the screening visit (measured at least twice using the same assay) and not experienced two consecutive HIV-1 RNA above detectable levels after achieving a confirmed (two consecutive) HIV-1 RNA below detectable levels on the current regimen in the past year. - Plasma HIV-1 RNA should be < 50 copies/mL at the screening visit. - Normal electrocardiogram (ECG) - Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × the upper limit of the normal range (ULN) - Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin (individuals with documented Gilbert's syndrome or with Atazanavir-associated hyperbilirubinemia may have total bilirubin up to 5 x ULN) - Adequate hematologic function - Serum amylase ≤ 5 × ULN - Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active, or practice abstinence from screening throughout the duration of the study treatment and for 30 days following the last dose of the study drug. - Females who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range. - Females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing. - Males must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose. Exclusion Criteria: - A new AIDS-defining condition diagnosed within the 30 days prior to screening - Hepatitis C virus (HCV) antibody positive and HCV RNA detectable - Individuals experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.) - Individuals receiving ongoing treatment with bisphosphonate to treat bone disease (eg, osteoporosis) - Females who are breastfeeding - Positive serum pregnancy test - Have an implanted defibrillator or pacemaker - Current alcohol or substance use judged by the investigator to potentially interfere with study compliance - A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. - Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 Visit - Individuals receiving ongoing therapy with any of the medications not to be used with FTC, TAF, TDF or other antiretroviral third agents.

Additional Information

Official title A Phase 3, Randomized, Double-Blind, Switch Study to Evaluate F/TAF in HIV-1 Positive Subjects Who Are Virologically Suppressed on Regimens Containing FTC/TDF
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by Gilead Sciences.