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

Gilead Sciences55 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HIV-1 Infection

Interventions

E/C/F/TAFDRUG

150/150/200/10 mg FDC tablets administered orally once daily

B/F/TAFDRUG

50/200/25 mg FDC tablets administered orally once daily

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (26)

Peter J Ruane MD Inc

Outcomes

Primary Outcomes

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).

Time frame: First Dose Date Up to Week 48

Secondary Outcomes

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).

Time frame: 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.

Data from ClinicalTrials.gov

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Los Angeles, California, United States

University of California Davis

Sacramento, California, United States

Midway Immunology & Research Center, LLC

Ft. Pierce, Florida, United States

Infectious Disease Consultants, M.D., P.A. d/b/a Orlando Immunology Center

Orlando, Florida, United States

Triple O Research Institute PA

West Palm Beach, Florida, United States

Medical College of Georgia

Augusta, Georgia, United States

Infectious Disease Specialists of Atlanta

Decatur, Georgia, United States

Mercer University School of Medicine

Macon, Georgia, United States

The Research Institute

Springfield, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

...and 16 more locations

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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Week 48 of the BVY OL Extension Phase

GEN Phase: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 96

Time frame: Baseline; Week 96

BVY OL Extension Phase: Change From Baseline in CD4+ Cell Count at Week 48

Time frame: Baseline; Week 48 of the BVY OL Extension Phase

GEN Phase: Change From Baseline in CD4 Percentage at Week 96

Time frame: Baseline; Week 96

BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48

Time frame: Baseline; Week 48 of the BVY OL Extension Phase