Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Adults on Chronic Hemodialysis

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety and tolerability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) in human immunodeficiency virus (HIV-1) infected adults with end-stage renal disease (ESRD) on chronic hemodialysis (HD).

Official Title
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A Phase 3b Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Subjects on Chronic Hemodialysis

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: E/C/F/TAF
* Drug: B/F/TAF


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Currently on a stable antiretroviral regimen for ≥ 6 consecutive months Plasma HIV-1 ribonucleic acid (RNA) concentrations < 50 copies/mL for ≥ 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at screening No documented history of HIV-1 resistance to elvitegravir (EVG), emtricitabine (FTC), lamivudine (3TC) or tenofovir (TFV) and no history of switching off EVG, FTC, 3TC or TFV due to concern for resistance Cluster determinant 4 (CD4+) T cell count ≥ 200 cells/μL ESRD with estimated glomerular filtration rate (eGFR) < 15 mL/min by Cockcroft-Gault formula for creatinine clearance On chronic HD for ≥ 6 months prior to screening Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥ 50,000/mm^3; hemoglobin ≥ 8.5 g/dL) Key Exclusion Criteria: Hepatitis B co-infection Any clinical history, condition, or test result that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements Administration of other investigational agents (unless approved by Gilead Sciences). Participation in any other clinical trial, including observational trials, without prior approval from the sponsor is prohibited while participating in this trial. History or presence of allergy or intolerance to the study drugs or their components A new acquired immunodeficiency syndrome (AIDS)-defining condition (excluding CD4+ T cell count and percentage criteria) diagnosed within the 30 days prior to screening, with the exception of oropharyngeal candidiasis Received solid organ or bone marrow transplant 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E/C/F/TAF<br>Participants will switch their current antiretroviral regimen to E/C/F/TAF and receive treatment for 96 weeks. After Week 96, participants in the United States (US) who wish to participate in the open-label (OL) rollover extension will continue to take E/C/F/TAF FDC until the End of E/C/F/TAF Visit. | Drug: E/C/F/TAF<br>* 150/150/200/10 mg FDC tablets administered orally once daily<br>* Other names: Genvoya®;|
| Experimental: Open-Label Rollover Extension B/F/TAF<br>At Week 96 or the End of E/C/F/TAF Visit (whichever occurs last), participants will be given the option to receive open-label bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for at least 48 weeks. | Drug: B/F/TAF<br>* 50/200/25 mg FDC tablets administered orally once daily<br>* Other names: Biktarvy®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 48 | Treatment-emergent Adverse Events (TEAE) were defined as AEs with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of the E/C/F/TAF (GEN Phase) study drug or all AEs for participants still on E/C/F/TAF. It also includes the AEs that led to premature discontinuation of E/C/F/TAF study drug. Clinical events and clinically significant laboratory abnormalities were graded according to the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities. Adverse events were graded as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life threatening). | First Dose Date Up to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 96 | Treatment-emergent Adverse Events (TEAE) were defined as events that met 1 or both of the following criteria as any AEs with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of the E/C/F/TAF (GEN Phase) study drug for participants who did not participate in the BVY OL extension phase or the day prior to the date of the first B/F/TAF study drug dose for participants who participated in the BVY OL extension phase. It also includes the AEs that led to premature discontinuation of E/C/F/TAF study drug. Clinical events and clinically significant laboratory abnormalities were graded according to the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities. Adverse events were graded as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life threatening). | First Dose Date Up to Week 96 | 
| GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 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 24 | 
| GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA 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 | 
| GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the FDA 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 | 
| Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG), Cobicistat (COBI), Emtricitabine (FTC), and Tenofovir (TFV) | AUCtau is defined as area under the concentration versus time curve over the dosing interval (i.e., concentration of drug over time). | 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 | 
| PK Parameter: AUClast of EVG, COBI, FTC, Tenofovir Alafenamide (TAF), and TFV | AUClast is defined as the area under the concentration versus time curve from time zero to the last observable concentration. | 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 | 
| PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV | Cmax is defined as the maximum concentration of drug. | 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 | 
| PK Parameter: Ctau of EVG, COBI, FTC, and TFV | Ctau is defined as the observed drug concentration at the end of the dosing interval. Ctau has been presented in lieu of Cmin (specified in the protocol) to align with other Gilead studies. This change has no impact on the PK analysis as Ctau and Cmin are equivalent for all analytes. | 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 | 
| GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Failure (M = F) Approach | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 were analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL. | Week 96 | 
| GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Excluded (M = E) Approach | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 were analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions. | Week 96 | 
| BVY OL Extension Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = E Approach | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 were analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions. | Week 48 of the BVY OL Extension Phase | 
| GEN Phase: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 96 |  | Baseline; Week 96 | 
| BVY OL Extension Phase: Change From Baseline in CD4+ Cell Count at Week 48 |  | Baseline; Week 48 of the BVY OL Extension Phase | 
| GEN Phase: Change From Baseline in CD4 Percentage at Week 96 |  | Baseline; Week 96 | 
| BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48 |  | Baseline; Week 48 of the BVY OL Extension Phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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End stage renal disease, Hemodialysis, Open-label, HIV-1 Infection