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

NCT02600819 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-292-18252015-002713-30
• Study Type: interventional
• Target: 55
• Locations: 4 countries
• Sites: 26

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).

Conditions

HIV-1 Infection

Keywords

End stage renal disease; Hemodialysis; Open-label; HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• 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

• GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm

  Week 24

• GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm

  Week 48

• GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the FDA Snapshot Algorithm

  Week 96

• 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

Study Arms (2)

E/C/F/TAF

EXPERIMENTAL

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

Open-Label Rollover Extension B/F/TAF

EXPERIMENTAL

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

Interventions

E/C/F/TAF DRUG

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

Also known as: Genvoya®

E/C/F/TAF

B/F/TAF DRUG

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

Also known as: Biktarvy®

Open-Label Rollover Extension B/F/TAF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (26)

Peter J Ruane MD Inc

Los Angeles, California, United States

Location

University of California Davis

Sacramento, California, United States

Location

Midway Immunology & Research Center, LLC

Ft. Pierce, Florida, United States

Location

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

Orlando, Florida, United States

Location

Triple O Research Institute PA

West Palm Beach, Florida, United States

Location

Medical College of Georgia

Augusta, Georgia, United States

Location

Infectious Disease Specialists of Atlanta

Decatur, Georgia, United States

Location

Mercer University School of Medicine

Macon, Georgia, United States

Location

The Research Institute

Springfield, Massachusetts, United States

Location

Henry Ford Health System

Detroit, Michigan, United States

Location

Prime Health Care Services - St Michael's LLC d/b/a Saint Michael's Medical Center

Newark, New Jersey, United States

Location

University of North Carolina at Chapel Hill / UNC School of Medicine

Chapel Hill, North Carolina, United States

Location

Duke University

Durham, North Carolina, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Location

University of Cincinnati Med Center

Cincinnati, Ohio, United States

Location

MetroHealth Medical Center IRB

Cleveland, Ohio, United States

Location

North Texas Infectious Diseases Consultants

Dallas, Texas, United States

Location

Trinity Health and Wellness Center

Fort Worth, Texas, United States

Location

Gordon E. Crofoot MD PA

Houston, Texas, United States

Location

Otto Wagner Spital

Vienna, Austria

Location

Hopital Henri Mondor

Créteil, France

Location

CHU de Nice-l Archet

Nice, France

Location

Hopital Bichat-Claude Bernard

Paris, France

Location

Hopital Saint Louis

Paris, France

Location

Centre Hospitalier de Tourcoing

Tourcoing, France

Location

Klinikum rechts der Isar, TUM

München, Germany

Location

Related Publications (1)

• 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.

  PMID: 30555051 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; bictegravir, emtricitabine, tenofovir alafenamide, drug combination

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cobicistat; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2015
• First Posted: November 9, 2015
• Study Start: December 14, 2015
• Primary Completion: September 29, 2017
• Study Completion: October 15, 2019
• Last Updated: November 5, 2020
• Results First Posted: October 16, 2018

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

US (19); FR (5); AU (1); DE (1)