Switch Study to Evaluate F/TAF in HIV-1 Positive Participants Who Are Virologically Suppressed on Regimens Containing FTC/TDF

Phase 3

Completed

Conditions: HIV-1 Infection

Interventions: Drug: FTC/TDF
Drug: F/TAF
Drug: Allowed third antiretroviral agent
Drug: FTC/TDF Placebo
Drug: F/TAF Placebo

Registration Number: NCT02121795

Lead Sponsor: Gilead Sciences

Brief Summary: This study will evaluate the efficacy of switching from emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) fixed dose combination (FDC) to emtricitabine/tenofovir alafenamide (F/TAF) FDC in HIV-1 positive participants who are virologically suppressed on regimens containing FTC/TDF.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 668

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.

Key

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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FTC/TDF + 3rd Agent	Allowed third antiretroviral agent	Participants will receive FTC/TDF plus F/TAF placebo while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks.
F/TAF + 3rd Agent	Allowed third antiretroviral agent	Participants will receive F/TAF (200/25 mg or 200/10 mg) plus FTC/TDF placebo 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 + 3rd Agent	FTC/TDF Placebo	Participants will receive F/TAF (200/25 mg or 200/10 mg) plus FTC/TDF placebo 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.
FTC/TDF + 3rd Agent	F/TAF Placebo	Participants will receive FTC/TDF plus F/TAF placebo while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks.
FTC/TDF + 3rd Agent	FTC/TDF	Participants will receive FTC/TDF plus F/TAF placebo while remaining on an allowed third antiretroviral agent of the participant's pre-existing treatment regimen, for 96 weeks.
F/TAF + 3rd Agent	F/TAF	Participants will receive F/TAF (200/25 mg or 200/10 mg) plus FTC/TDF placebo 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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis	Week 48	The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Secondary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in Spine BMD at Week 96	Baseline; Week 96	Spine BMD was assessed by DXA scan.
Change From Baseline in CD4+ Cell Count at Week 96	Baseline; Week 96
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the FDA Snapshot Analysis	Week 48	The percentage of participants achieving HIV-1 RNA \< 20 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Change From Baseline in CD4+ Cell Count at Week 48	Baseline; Week 48
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 as Defined by the FDA Snapshot Analysis	Week 96	The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Percentage Change From Baseline in Hip BMD at Week 96	Baseline; Week 96	Hip BMD was assessed by DXA scan.
Percentage Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48	Baseline; Week 48	Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the FDA Snapshot Analysis	Week 96	The percentage of participants achieving HIV-1 RNA \< 20 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Percentage Change From Baseline in Spine BMD at Week 48	Baseline; Week 48	Spine BMD was assessed by DXA scan.

Trial Locations

Locations (77): University of Alabama at Birmingham
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Birmingham, Alabama, United States
Spectrum Medical Group
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Phoenix, Arizona, United States
Pacific Oaks Medical Group
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Beverly Hills, California, United States
Kaiser Permanente
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Hayward, California, United States
Tarrant County ID Associates
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Los Angeles, California, United States
Southern California Men's Medical Group
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Los Angeles, California, United States
Highland Hospital - Alameda Health System (formerly Alameda County medical Center)
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Oakland, California, United States
Kaiser Permanente Sacramento Medical Center
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Sacramento, California, United States
La Playa Medical Group and Clinical Research
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San Diego, California, United States
Kaiser Permanente Medical Group San Francisco
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San Francisco, California, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States