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

NCT ID: NCT02605954

Last Updated: 2018-11-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

275 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-18

Study Completion Date

2018-01-24

Brief Summary

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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.

Detailed Description

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Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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E/C/F/TAF

Participants will switch to E/C/F/TAF FDC and receive treatment for 48 weeks.

Group Type EXPERIMENTAL

E/C/F/TAF

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

ABC/3TC

Intervention Type DRUG

600/300 mg tablets administered orally once daily

Third Antiretroviral Agent

Intervention Type DRUG

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

Interventions

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E/C/F/TAF

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

Intervention Type DRUG

ABC/3TC

600/300 mg tablets administered orally once daily

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

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Genvoya® Epzicom Kivexa

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Spectrum Medical Group

Phoenix, Arizona, United States

Site Status

Ruane Clinical Research Group

Los Angeles, California, United States

Site Status

Capital Medical Associates, P.C.

Washington D.C., District of Columbia, United States

Site Status

Georgetown University

Washington D.C., District of Columbia, United States

Site Status

Gary Richmond, MD, PA, Inc.

Fort Lauderdale, Florida, United States

Site Status

Midway Immunology & Research Center, LLC

Ft. Pierce, Florida, United States

Site Status

Steinhart Medical Associates dba The Kinder Medical Group

Miami, Florida, United States

Site Status

Triple O Research Institute PA

West Palm Beach, Florida, United States

Site Status

The Positive Health Clinic, Allegheny Health Network

Pittsburgh, Pennsylvania, United States

Site Status

Central Texas Clinical Research

Austin, Texas, United States

Site Status

AIDS Arms, Inc./Trinity Health & Wellness Center

Dallas, Texas, United States

Site Status

Tarrant County ID Associates

Fort Worth, Texas, United States

Site Status

CHU - Groupe Saint-Andre

Bordeaux, , France

Site Status

Hopital Henri Mondor

Créteil, , France

Site Status

Hopital Europeen Marseille

Marseille, , France

Site Status

C.H.U. de Nantes

Nantes, , France

Site Status

C.H.U. de NICE

Nice, , France

Site Status

CHU Hotel Dieu

Paris, , France

Site Status

Hopital Lariboisiere

Paris, , France

Site Status

Hopital Necker les Enfants Malades

Paris, , France

Site Status

Hopital Saint Antoine

Paris, , France

Site Status

Hopital Saint Louis

Paris, , France

Site Status

Centre Hospitalier Gustave Dron

Tourcoing, , France

Site Status

Epimed GmbH

Berlin, , Germany

Site Status

Universitatsklinikum Essen

Essen, , Germany

Site Status

ICH Study Center Hamburg

Hamburg, , Germany

Site Status

Universitatsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status

ARNAS Garibaldi - Nesima

Catania, , Italy

Site Status

Unit Infectious Diseases - University of Catania - ARNAS Garibaldi

Catania, , Italy

Site Status

Azienda Ospedaliera Luigi Sacco

Milan, , Italy

Site Status

Azienda Ospedaliero Universitaria Policlinico di Modena

Modena, , Italy

Site Status

Azienda Ospedale San Paolo

Monza, , Italy

Site Status

Azienda Ospedaliera San Gerardo

Monza, , Italy

Site Status

Ospedale Civile S. Spirito AUSL

Pescara, , Italy

Site Status

Unità Operativa Complessa di Malattie Infettive

Pescara, , Italy

Site Status

Istituto Nazionale Malattie Infettive Lazzaro Spallanzani I.R.C.C.S.

Roma, , Italy

Site Status

Comprensorio Ospedaliero Amedeo di Savoia

Torino, , Italy

Site Status

Dipartimento di Malattie Infettive e Tropicali

Torino, , Italy

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Costa Del Sol

Marbella, , Spain

Site Status

Hospital Reg. Univ. Carlos Haya

Málaga, , Spain

Site Status

Hospital Clínico Universitario de Valencia (Galindo)

Valencia, , Spain

Site Status

Hospital General Universitario de Valencia (Abril)

Valencia, , Spain

Site Status

Hospital Alvaro Cunqueiro

Vigo, , Spain

Site Status

Mortimer Market Centre

London, , United Kingdom

Site Status

Countries

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United States France Germany Italy Spain United Kingdom

References

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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

Reference Type BACKGROUND

Provided Documents

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Document Type: Study Protocol: Original

View Document

Document Type: Study Protocol: Amendment 1

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-002711-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-292-1823

Identifier Type: -

Identifier Source: org_study_id

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