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

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

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 Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: E/C/F/TAF; Drug: B/F/TAF

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria
    • Otto Wagner Spital
• France
  • Creteil, France
    • Hôpital Henri Mondor
  • NICE Cedex 03, France
    • CHU de Nice-l Archet
  • Paris, France
    • Hopital Bichat-Claude Bernard
  • Paris Cedex 10, France
    • Hopital Saint Louis
  • Tourcoing Cedex, France
    • Centre Hospitalier de Tourcoing
• Germany
  • Munchen, Germany
    • Klinikum rechts der Isar, TUM
• United States
  • California
    • Los Angeles, California, United States
      • Peter J Ruane Md Inc
    • Sacramento, California, United States
      • University of California Davis
  • Florida
    • Fort Pierce, Florida, United States
      • Midway Immunology & Research Center, LLC
    • Orlando, Florida, United States
      • Infectious Disease Consultants, M.D., P.A. d/b/a Orlando Immunology Center
    • West Palm Beach, Florida, United States
      • Triple O Research Institute PA
  • Georgia
    • Augusta, Georgia, United States
      • Medical College of Georgia
    • Decatur, Georgia, United States
      • Infectious Disease Specialists of Atlanta
    • Macon, Georgia, United States
      • Mercer University School of Medicine
  • Massachusetts
    • Springfield, Massachusetts, United States
      • The Research Institute
  • Michigan
    • Detroit, Michigan, United States
      • Henry Ford Health System
  • New Jersey
    • Newark, New Jersey, United States
      • Prime Health Care Services - St Michael's LLC d/b/a Saint Michael's Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States
      • University of North Carolina at Chapel Hill / UNC School of Medicine
    • Durham, North Carolina, United States
      • Duke University
    • Winston-Salem, North Carolina, United States
      • Wake Forest University Baptist Medical Center
  • Ohio
    • Cincinnati, Ohio, United States
      • University of Cincinnati Med Center
    • Cleveland, Ohio, United States
      • MetroHealth Medical Center IRB
  • Texas
    • Dallas, Texas, United States
      • North Texas Infectious Diseases Consultants
    • Fort Worth, Texas, United States
      • Trinity Health and Wellness Center
    • Houston, Texas, United States
      • Gordon E. Crofoot MD PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: E/C/F/TAF; 150/150/200/10 mg FDC tablets administered orally once daily; Other Names: Genvoya®
EXPERIMENTAL: Open-Label Rollover Extension 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.	Drug: B/F/TAF; 50/200/25 mg FDC tablets administered orally once daily; Other Names: Biktarvy®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Eron JJ Jr, Lelievre JD, Kalayjian R, Slim J, Wurapa AK, Stephens JL, McDonald C, Cua E, Wilkin A, Schmied B, McKellar M, Cox S, Majeed SR, Jiang S, Cheng A, Das M, SenGupta D. Safety of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in HIV-1-infected adults with end-stage renal disease on chronic haemodialysis: an open-label, single-arm, multicentre, phase 3b trial. Lancet HIV. 2018 Dec 13:S2352-3018(18)30296-0. doi: 10.1016/S2352-3018(18)30296-0. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 14, 2015
• Primary Completion (ACTUAL): September 29, 2017
• Study Completion (ACTUAL): October 15, 2019

Study Registration Dates

• First Submitted: November 6, 2015
• First Submitted That Met QC Criteria: November 6, 2015
• First Posted (ESTIMATE): November 9, 2015

Study Record Updates

• Last Update Posted (ACTUAL): November 5, 2020
• Last Update Submitted That Met QC Criteria: October 13, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Open-label; End stage renal disease; Hemodialysis; HIV-1 Infection
• Additional Relevant MeSH Terms: Infections; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: GS-US-292-1825; 2015-002713-30 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No