Safety and Efficacy of Switching From Regimens of ABC/3TC + a 3rd Agent to E/C/F/TAF Fixed-Dose Combination (FDC) in Virologically-Suppressed HIV 1 Infected Adults

A Phase 3b, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Abacavir/Lamivudine (ABC/3TC) Plus a Third Antiretroviral Agent to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed HIV 1 Infected Adult Subjects

The primary objective of this study is to evaluate the efficacy of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) relative to continuing on a baseline regimen consisting of abacavir/lamivudine (ABC/3TC) plus a 3rd antiretroviral agent in HIV-1 infected participants.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: E/C/F/TAF; Drug: ABC/3TC; Drug: Third Antiretroviral Agent

• Study Type: Interventional
• Enrollment (Actual): 275
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • CHU - Groupe Saint-Andre
  • Creteil, France
    • Hopital Henri Mondor
  • Marseille, France
    • Hôpital Européen Marseille
  • Nantes, France
    • C.H.U. de Nantes
  • Nice, France
    • C.H.U. de NICE
  • PARIS cedex 10, France
    • Hopital Saint Louis
  • Paris, France
    • Hopital Lariboisiere
  • Paris, France
    • Hopital Necker les Enfants Malades
  • Paris Cedex 14, France
    • Chu Hotel Dieu
  • Paris cedex 12, France
    • Hôpital Saint Antoine
  • Tourcoing, France
    • Centre Hospitalier Gustave Dron
• Germany
  • Berlin, Germany
    • EPIMED GmbH
  • Essen, Germany
    • Universitätsklinikum Essen
  • Hamburg, Germany
    • Universitatsklinikum Hamburg-Eppendorf
  • Hamburg, Germany
    • ICH Study Center Hamburg
• Italy
  • Catania, Italy
    • ARNAS Garibaldi - Nesima
  • Catania, Italy
    • Unit Infectious Diseases - University of Catania - ARNAS Garibaldi
  • Milano, Italy
    • Azienda Ospedaliera Luigi Sacco
  • Modena, Italy
    • Azienda Ospedaliero Universitaria Policlinico di Modena
  • Monza, Italy
    • Azienda Ospedaliera San Gerardo
  • Monza, Italy
    • Azienda Ospedale San Paolo
  • Pescara, Italy
    • Ospedale Civile S. Spirito AUSL
  • Pescara, Italy
    • Unità Operativa Complessa di Malattie Infettive
  • Roma, Italy
    • Istituto Nazionale Malattie Infettive Lazzaro Spallanzani I.R.C.C.S.
  • Torino, Italy
    • Dipartimento di Malattie Infettive e Tropicali
  • Torino, Italy
    • Comprensorio Ospedaliero Amedeo di Savoia
• Spain
  • Barcelona, Spain
    • Hospital Clinic De Barcelona
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Hospital de la Santa Creu i Sant Pau
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Marbella, Spain
    • Hospital Costa del Sol
  • Málaga, Spain
    • Hospital Reg. Univ. Carlos Haya
  • Valencia, Spain
    • Hospital Clínico Universitario de Valencia (Galindo)
  • Valencia, Spain
    • Hospital General Universitario de Valencia (Abril)
  • Vigo, Spain
    • Hospital Álvaro Cunqueiro
• United Kingdom
  • London, United Kingdom
    • Mortimer Market Centre
• United States
  • Arizona
    • Phoenix, Arizona, United States
      • Spectrum Medical Group
  • California
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group
  • District of Columbia
    • Washington, District of Columbia, United States
      • Capital Medical Associates, P.C.
    • Washington, District of Columbia, United States
      • Georgetown University
  • Florida
    • Fort Lauderdale, Florida, United States
      • Gary Richmond, MD, PA, Inc.
    • Fort Pierce, Florida, United States
      • Midway Immunology & Research Center, LLC
    • Miami, Florida, United States
      • Steinhart Medical Associates dba The Kinder Medical Group
    • West Palm Beach, Florida, United States
      • Triple O Research Institute PA
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
      • The Positive Health Clinic, Allegheny Health Network
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Dallas, Texas, United States, 75208
      • AIDS Arms, Inc./Trinity Health & Wellness Center
    • Fort Worth, Texas, United States, 76104
      • Tarrant County ID Associates

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:

HIV-infected adult participants who meet the following criteria will be given the option to participate in the study:

• Currently receiving ABC/3TC plus a third antiretroviral (ARV) agent for ≥ 6 consecutive months preceding the screening visit. For subjects with 3 or more ART regimens, a regimen history must be provided to the Sponsor for approval. Allowed third antiretroviral agents include LPV/r, ATV+RTV, ATV+COBI (or ATV/COBI FDC), DRV+RTV, DRV + COBI (or DRV/COBI FDC) FPV + RTV, SQV + RTV, ATV (no booster), EFV, RPV, NVP, ETR, RAL or DTG
• Documented plasma HIV-1 RNA levels < 50 copies/mL for ≥ 6 months preceding the screening visit (measured at least twice using the same assay). In the preceding 6 months prior to screening, one episode of "blip" (HIV-1 RNA > 50 and < 400 copies/mL) is acceptable, only if HIV-1 RNA is < 50 copies/mL immediately before and after the "blip".
• Plasma HIV-1 RNA < 50 copies/mL at screening visit
• Individuals will have no evidence of previous virologic failure on a PI+RTV or integrase strand transfer inhibitor-based regimen (with or without resistance to either class of ARV).
• All documented historical plasma genotype(s) must not show resistance to tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC), including, but not limited to the presence of reverse transcriptase resistance mutants K65R, K70E, M184V/I, or thymidine analog associated mutations (TAMs) (TAMs are: M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). If a historical genotype is not available or subject has 3 or more ART regimens, subject will have proviral genotype analysis prior to Day 1 to confirm absence of archived resistance to TDF or FTC.
• Adequate renal function defined as having an estimated glomerular filtration rate of ≥ 30 mL/min as calculated by Cockcroft-Gault (eGFR-CG)

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: E/C/F/TAF; Participants will switch to E/C/F/TAF FDC and receive treatment for 48 weeks.	Drug: E/C/F/TAF; 150/150/200/10 mg FDC tablets administered orally once daily; Other Names: Genvoya®
Active Comparator: ABC/3TC+3rd Agent; Participants will maintain prior regimen of ABC/3TC plus a third antiretroviral agent for 24 weeks followed by a delayed switch to E/C/F/TAF FDC. Note: the prior regimen is determined by the participant's clinician (prior to entry into the study) and will consist of one of the third antiretroviral agents listed.	Drug: ABC/3TC; 600/300 mg tablets administered orally once daily; Other Names: Kivexa; Epzicom; Drug: Third Antiretroviral Agent; Third antiretroviral agents could include one of the following: ATV+cobicistat (COBI; Tybost®) or ATV/COBI FDC; DRV+COBI or DRV/COBI FDC; darunavir (DRV; Prezista®) + RTV; lopinavir/ritonavir (LPV/r; Kaletra®); atazanavir (ATV; Reyataz®) + ritonavir (RTV; Norvir®); efavirenz (EFV; Sustiva®); etravirine (ETR; Intelence®); nevirapine (NVP; Viramune®); rilpivirine (RPV; Edurant®); dolutegravir (DTG; Tivicay®); raltegravir (RAL; Isentress®); fosamprenavir (FPV; Lexiva®) + RTV; saquinavir (SQV; Invirase®) + RTV; ATV (no booster) Drug classes: Protease inhibitors (PI): LPV/r, ATV, RTV, ATV, DRV, FPV and SQV; Pharmacokinetic enhancer: COBI; Non-nucleoside reverse transcriptase inhibitors (NNRTI): EFV, RPV, NVP, and ETR; Integrase inhibitors: RAL and DTG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 24	The percentage of participants achieving 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48
Change From Baseline in CD4+ Cell Count at Week 24		Baseline; Week 24
Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 12	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 12 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 12
Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 48	The percentage of participants achieving 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

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• A Gori, G Rizzardini, C Miralles, J Olalla, JM Molina, F Raffi, P Kumar, A Antinori, M Ramgopal, HJ Stellbrink, M Das, H Chu, R Ram, W Garner, SK Chuck, D Piontkowsky, R Haubrich. Switching from An Abacavir (ABC)/Lamivudine (3TC)-Based Regimen to a Single-Tablet Regimen of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) is Efficacious and Safe: Week 24 Primary Analysis of a Randomized Controlled Study in Virologically-Suppressed Adults [Presentation]. XVIII Congrès National de la SFLS, 19-20 October 2017, Nice Acropolis, France

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2015
• Primary Completion (Actual): June 14, 2017
• Study Completion (Actual): January 24, 2018

Study Registration Dates

• First Submitted: November 13, 2015
• First Submitted That Met QC Criteria: November 13, 2015
• First Posted (Estimate): November 17, 2015

Study Record Updates

• Last Update Posted (Actual): November 14, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: HIV; Antiretroviral agents; HIV 1 Infection; Virologically-Suppressed
• Additional Relevant MeSH Terms: Infections; Anti-Infective Agents; Antiviral Agents; Anti-Retroviral Agents
• Other Study ID Numbers: GS-US-292-1823; 2015-002711-15 (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 http://www.gilead.com/research/disclosure-and-transparency.
• 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