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
- Registration Number
- NCT02600819
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 55
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Open-Label Rollover Extension B/F/TAF B/F/TAF 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. E/C/F/TAF E/C/F/TAF 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.
- Primary Outcome Measures
Name Time Method GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 48 First Dose Date 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).
- Secondary Outcome Measures
Name Time Method GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the FDA Snapshot Algorithm Week 96 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.
Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG), Cobicistat (COBI), Emtricitabine (FTC), and Tenofovir (TFV) 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 AUCtau is defined as area under the concentration versus time curve over the dosing interval (i.e., concentration of drug over time).
GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 96 First Dose Date 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).
GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm Week 24 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.
GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Excluded (M = E) Approach Week 96 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.
BVY OL Extension Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = E Approach Week 48 of the BVY OL Extension Phase 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.
GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Failure (M = F) Approach Week 96 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.
GEN Phase: Change From Baseline in CD4 Percentage at Week 96 Baseline; Week 96 GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm Week 48 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.
BVY OL Extension Phase: Change From Baseline in CD4+ Cell Count at Week 48 Baseline; Week 48 of the BVY OL Extension Phase PK Parameter: AUClast of EVG, COBI, FTC, Tenofovir Alafenamide (TAF), and TFV 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 AUClast is defined as the area under the concentration versus time curve from time zero to the last observable concentration.
GEN Phase: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 96 Baseline; Week 96 PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 Cmax is defined as the maximum concentration of drug.
PK Parameter: Ctau of EVG, COBI, FTC, and TFV 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4 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.
BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48 Baseline; Week 48 of the BVY OL Extension Phase
Trial Locations
- Locations (26)
Otto Wagner Spital
🇦🇹Wien, Austria
Hopital Bichat-Claude Bernard
🇫🇷Paris, France
Mercer University School of Medicine
🇺🇸Macon, Georgia, United States
University of North Carolina at Chapel Hill / UNC School of Medicine
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest University Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Duke University
🇺🇸Durham, North Carolina, United States
MetroHealth Medical Center IRB
🇺🇸Cleveland, Ohio, United States
North Texas Infectious Diseases Consultants
🇺🇸Dallas, Texas, United States
Trinity Health and Wellness Center
🇺🇸Fort Worth, Texas, United States
University of Cincinnati Med Center
🇺🇸Cincinnati, Ohio, United States
Gordon E. Crofoot MD PA
🇺🇸Houston, Texas, United States
Peter J Ruane MD Inc
🇺🇸Los Angeles, California, United States
University of California Davis
🇺🇸Sacramento, California, 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
Infectious Disease Specialists of Atlanta
🇺🇸Decatur, Georgia, United States
Medical College of Georgia
🇺🇸Augusta, Georgia, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Prime Health Care Services - St Michael's LLC d/b/a Saint Michael's Medical Center
🇺🇸Newark, New Jersey, United States
Centre Hospitalier de Tourcoing
🇫🇷Tourcoing Cedex, France
Klinikum rechts der Isar, TUM
🇩🇪Munchen, Germany
Midway Immunology & Research Center, LLC
🇺🇸Fort Pierce, Florida, United States
Hopital Henri Mondor
🇫🇷Creteil, France
CHU de Nice-l Archet
🇫🇷NICE Cedex 03, France
Hopital Saint Louis
🇫🇷Paris Cedex 10, France
The Research Institute
🇺🇸Springfield, Massachusetts, United States