Study to Evaluate Switching From a TDF-Containing Combination Regimen to a TAF-Containing Fixed Dose Combination (FDC) in Virologically-Suppressed, HIV-1 Positive Participants

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the non-inferiority of switching to a tenofovir alafenamide (TAF)-containing fixed dose combination (FDC) relative to maintaining tenofovir disoproxil fumarate (TDF)-containing combination regimens in virologically suppressed HIV-infected participants as determined by having HIV-1 RNA < 50 copies/mL at Week 48.

Official Title
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A Phase 3, Open-Label Study to Evaluate Switching From a TDF-Containing Combination Regimen to a TAF-Containing Combination Single Tablet Regimen (STR) in Virologically-Suppressed, HIV-1 Positive Subjects

Conditions
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HIV, HIV Infections

Intervention / Treatment
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* Drug: E/C/F/TAF
* Drug: E/C/F/TDF
* Drug: EFV/FTC/TDF
* Drug: RTV
* Drug: ATV
* Drug: FTC/TDF
* Drug: COBI


Participation Criteria
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Eligibility Criteria
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Key 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 therapy consisting of E/C/F/TDF, EFV/FTC/TDF, RTV+ATV+FTC/TDF, or COBI+ATV+FTC/TDF for ≥ 6 consecutive months preceding the final visit in their earlier study Completion of the Week 144 visit in studies GS-US-236-0102, GS-US-236-0103, GS-US-216-0114, or completion of the Week 96 visit in study GS-US-264-0110 (only participants on an EFV-based regimen), or completion of studies GS-US-236-0104, GS-US-216-0105 Plasma human immunodeficiency virus type 1-ribonucleic acid (HIV-1 RNA) concentrations at undetectable levels for at least 6 consecutive months prior to the screening visit and have HIV RNA < 50 copies/mL at the screening visit Normal echocardiograph (ECG) Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) ≤ 5 × upper limit of the normal range (ULN) Direct bilirubin ≤ 1.5 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 sexual abstinence from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drug if receiving EFV/FTC/TDF regimen, and 30 days for those assigned to all other regimens. Female participants 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 Female participants 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 Key Exclusion Criteria: A new acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening Hepatitis B surface antigen position Hepatitis C antibody positive Participants experiencing decompensated cirrhosis 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 subject study compliance History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial Participants receiving ongoing therapy with drugs not to be used with elvitegravir (EVG), COBI, FTC, TDF, ATV, RTV, EFV, and TAF or participants with any known allergies to the excipients of E/C/F/TDF, E/C/F/TAF, EFV/FTC/TDF, ATV, COBI, RTV, or FTC/TDF 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E/C/F/TAF<br>Randomized Phase: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) for up to 96 weeks. Extension Phase: After completing 96 weeks of randomized treatment, all participants will be given the opportunity to receive open-label E/C/F/TAF until it becomes commercially available, or until Gilead elects to terminate the development of E/C/F/TAF. | Drug: E/C/F/TAF<br>* 150/150/200/10 mg FDC tablet administered orally once daily<br>* Other names: EVG/COBI/FTC/TAF; Genvoya®;|
| Active Comparator: Stay on Baseline Treatment Regimen (SBR)<br>Randomized Phase: Participants stayed on their baseline emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)-containing regimen E/C/F/TDF; efavirenz (EFV)/FTC/TDF; ritonavir (RTV)-boosted atazanavir (ATV)+FTC/TDF; or cobicistat (COBI-boosted ATV+FTC/TDF) administered according to prescribing information for up to 96 weeks. Extension Phase: After completing 96 weeks of randomized treatment (SBR), all participants will be given the opportunity to receive open-label E/C/F/TAF until it becomes commercially available, or until Gilead elects to terminate the development of E/C/F/TAF. | Drug: E/C/F/TDF<br>* 150/150/200/300 mg FDC tablet administered orally once daily<br>* Other names: Stribild®;Drug: EFV/FTC/TDF<br>* 600/200/300 mg FDC tablet administered orally once daily<br>* Other names: Atripla®;Drug: RTV<br>* 100 mg tablet administered orally once daily<br>* Other names: Norvir®;Drug: ATV<br>* 300 mg capsule administered orally once daily<br>* Other names: Reyataz®;Drug: FTC/TDF<br>* 200/300 mg tablet administered orally once daily<br>* Other names: Truvada®;Drug: COBI<br>* 150 mg tablet administered orally once daily<br>* Other names: GS-9350;|

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 | The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient'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 |
| --- | --- | --- |
| Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 | Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan. BMD is calculated as grams per square centimeter (g/cm^2); the mean (SD) percentage change is presented. | Baseline; Week 48 | 
| Percent Change From Baseline in Spine BMD at Week 48 | Spine BMD was assessed by DXA scan. BMD is calculated as g/cm^2; the mean (SD) percentage change is presented. | Baseline; Week 48 | 
| Change From Baseline in Serum Creatinine at Week 48 |  | Baseline; Week 48 | 
| Change From Baseline in the Overall EFV-related Symptom Assessment Score at Week 48 | The mean (SD) change of the overall EFV-related symptom assessment score is presented. The overall symptom score (ranging from 0 to 20) is the sum of the individual symptom scores ranging from 0 (no symptoms) to 4 (most severe symptoms) from the 5 EFV-related symptom assessments (dizziness, trouble sleeping, impaired concentration, sleepiness, and abnormal or vivid dream). A negative change from baseline indicates improvement. EFV-Related Symptom Analysis Set: participants who received EFV/FTC/TDF as prior treatment, received at least 1 dose of study drug, and completed EFV-related symptom assessments at the baseline visit and at least 1 postbaseline visit. | Baseline; Week 48 | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 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 patient'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 | The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient'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 | The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a patient'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 Cluster Determinant 4 (CD4) Cell Count at Week 48 | The analysis of CD4 cell count included values up to 1 day after the last dose date of randomized study drug.The change from baseline in CD4 cell count for the full analysis set was based on observed data (ie, Missing = Excluded) for the total and by the prior treatment regimen. | Baseline; Week 48 | 
| Change From Baseline in CD4 Cell Count at Weeks 96 | The analysis of CD4 cell count included values up to 1 day after the last dose date of randomized study drug.The change from baseline in CD4 cell count for the full analysis set was based on observed data (ie, Missing = Excluded) for the total and by the prior treatment regimen. | 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 Infected, Virologically-Suppressed