Switch Study to Evaluate F/TAF in HIV-1 Infected Adults Who Are Virologically Suppressed on Regimens Containing ABC/3TC

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of switching abacavir/lamivudine (ABC/3TC) fixed-dose combination (FDC) tablets to emtricitabine/tenofovir alafenamide (F/TAF) FDC tablets versus maintaining ABC/3TC in human immunodeficiency virus type 1 (HIV-1) infected adults who are virologically suppressed on regimens containing ABC/3TC.

Official Title
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A Phase 3b, Randomized, Double-Blind, Switch Study to Evaluate F/TAF in HIV-1 Infected Subjects Who Are Virologically Suppressed on Regimens Containing ABC/3TC

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: F/TAF
* Drug: ABC/3TC
* Drug: ABC/3TC Placebo
* Drug: F/TAF Placebo
* Drug: 3rd ARV agent


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: The ability to understand and sign a written informed consent form On antiretroviral regimen containing ABC/3TC FDC in combination with one 3rd agent for ≥ 6 consecutive months prior to screening Plasma HIV-1 RNA levels < 50 copies/mL for ≥ 6 months preceding the screening visit (measured at least twice using the same assay) and without experiencing 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 ECG Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the Cockcroft Gault formula for creatinine clearance Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN) Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin Adequate hematologic function Serum amylase ≤ 5 × ULN Females of childbearing potential and males must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following the last dose of study drug Key Exclusion Criteria: A new AIDS-defining condition diagnosed within the 30 days prior to screening Hepatitis B surface antigen (HBsAg) positive Individuals experiencing decompensated cirrhosis Individuals receiving ongoing treatment with bisphosphonate to treat bone disease (eg, osteoporosis) Pregnant or lactating females 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 Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements Participation in any other clinical trial (including observational trials) without prior approval Medications excluded due to the potential for interaction with emtricitabine (FTC), TAF, ABC or 3TC Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: F/TAF (Double-Blind)<br>F/TAF + ABC/3TC placebo + allowed 3rd antiretroviral (ARV) agent for 96 weeks After Week 96, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments have been unblinded. | Drug: F/TAF<br>* 200/10 mg FDC tablet (with boosted 3rd ARV agents) or 200/25 mg FDC tablet (with unboosted 3rd ARV agents) administered orally once daily<br>* Other names: Descovy®;Drug: ABC/3TC Placebo<br>* Tablets administered orally once daily<br>Drug: 3rd ARV agent<br>* An allowed 3rd ARV agent of the participant's pre-existing regimen may include one of the following boosted ARV agents: ritonavir boosted lopinavir (LPV/r), atazanavir (ATV) + ritonavir (RTV), ATV + cobicistat (COBI) or ATV/COBI FDC, darunavir (DRV) + RTV, DRV+COBI or DRV/COBI FDC; or, one of the following unboosted ARV agents: efavirenz (EFV), rilpivirine (RPV), raltegravir (RAL), dolutegravir (DTG), maraviroc (MVC), or nevirapine (NVP).<br>|
| Active Comparator: ABC/3TC (Double-Blind)<br>ABC/3TC + F/TAF placebo + allowed 3rd ARV agent for 96 weeks After Week 96, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments have been unblinded. | Drug: ABC/3TC<br>* 600/300 mg FDC tablets administered orally once daily<br>Drug: F/TAF Placebo<br>* Tablets administered orally once daily<br>Drug: 3rd ARV agent<br>* An allowed 3rd ARV agent of the participant's pre-existing regimen may include one of the following boosted ARV agents: ritonavir boosted lopinavir (LPV/r), atazanavir (ATV) + ritonavir (RTV), ATV + cobicistat (COBI) or ATV/COBI FDC, darunavir (DRV) + RTV, DRV+COBI or DRV/COBI FDC; or, one of the following unboosted ARV agents: efavirenz (EFV), rilpivirine (RPV), raltegravir (RAL), dolutegravir (DTG), maraviroc (MVC), or nevirapine (NVP).<br>|
| Experimental: Open-Label F/TAF<br>After the unblinding visit, in countries where F/TAF FDC is not commercially available, participants (except in certain countries such as the UK) will be given the option to receive open-label F/TAF (200/10 mg or 200/25 mg) FDC and attend study visits every 12 weeks until it becomes commercially available, or until Gilead terminates the study in that country. | Drug: F/TAF<br>* 200/10 mg FDC tablet (with boosted 3rd ARV agents) or 200/25 mg FDC tablet (with unboosted 3rd ARV agents) administered orally once daily<br>* Other names: Descovy®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm | 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 status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm | 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 status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. | Week 96 | 
| Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm | The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. | Week 48 | 
| Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm | The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. | Week 96 | 
| Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm | 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 status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. | Week 48 | 
| Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm | 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 status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. | Week 96 | 
| Change From Baseline in CD4 Cell Count at Week 48 |  | Baseline; Week 48 | 
| Change From Baseline in CD4 Cell Count at Week 96 |  | Baseline; Week 96 | 
| Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 |  | Baseline; Week 48 | 
| Percent Change From Baseline in Hip BMD at Week 96 |  | Baseline; Week 96 | 
| Percent Change From Baseline in Spine BMD at Week 48 |  | Baseline; Week 48 | 
| Percent Change From Baseline in Spine BMD at Week 96 |  | Baseline; Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, HIV-1 Positive, Virologically-Suppressed