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

NCT02605954 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: GS-US-292-18232015-002711-15
• Study Type: interventional
• Target: 275
• Locations: 6 countries
• Sites: 49

Brief Summary

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.

Conditions

HIV-1 Infection

Keywords

HIV 1 Infection; HIV; Virologically-Suppressed; Antiretroviral agents

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 12

  Week 12

• Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 48

  Week 48

• Change From Baseline in CD4+ Cell Count at Week 24

  Baseline; Week 24

• Change From Baseline in CD4+ Cell Count at Week 48

  Baseline; Week 48

Study Arms (2)

E/C/F/TAF

EXPERIMENTAL

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

Drug: E/C/F/TAF

ABC/3TC+3rd Agent

ACTIVE COMPARATOR

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; Drug: Third Antiretroviral Agent

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

ABC/3TC DRUG

600/300 mg tablets administered orally once daily

Also known as: Epzicom, Kivexa

ABC/3TC+3rd Agent

Third Antiretroviral Agent 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

ABC/3TC+3rd Agent

Eligibility Criteria

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

You may qualify if:

• 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)

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (49)

Spectrum Medical Group

Phoenix, Arizona, United States

Location

Ruane Clinical Research Group

Los Angeles, California, 90036, United States

Location

Capital Medical Associates, P.C.

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

Location

Georgetown University

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

Location

Gary Richmond, MD, PA, Inc.

Fort Lauderdale, Florida, United States

Location

Midway Immunology & Research Center, LLC

Ft. Pierce, Florida, United States

Location

Steinhart Medical Associates dba The Kinder Medical Group

Miami, Florida, United States

Location

Triple O Research Institute PA

West Palm Beach, Florida, United States

Location

The Positive Health Clinic, Allegheny Health Network

Pittsburgh, Pennsylvania, United States

Location

Central Texas Clinical Research

Austin, Texas, 78705, United States

Location

AIDS Arms, Inc./Trinity Health & Wellness Center

Dallas, Texas, 75208, United States

Location

Tarrant County ID Associates

Fort Worth, Texas, 76104, United States

Location

CHU - Groupe Saint-Andre

Bordeaux, France

Location

Hopital Henri Mondor

Créteil, France

Location

Hopital Europeen Marseille

Marseille, France

Location

C.H.U. de Nantes

Nantes, France

Location

C.H.U. de NICE

Nice, France

Location

CHU Hotel Dieu

Paris, France

Location

Hopital Lariboisiere

Paris, France

Location

Hopital Necker les Enfants Malades

Paris, France

Location

Hopital Saint Antoine

Paris, France

Location

Hopital Saint Louis

Paris, France

Location

Centre Hospitalier Gustave Dron

Tourcoing, France

Location

Epimed GmbH

Berlin, Germany

Location

Universitatsklinikum Essen

Essen, Germany

Location

ICH Study Center Hamburg

Hamburg, Germany

Location

Universitatsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

ARNAS Garibaldi - Nesima

Catania, Italy

Location

Unit Infectious Diseases - University of Catania - ARNAS Garibaldi

Catania, Italy

Location

Azienda Ospedaliera Luigi Sacco

Milan, Italy

Location

Azienda Ospedaliero Universitaria Policlinico di Modena

Modena, Italy

Location

Azienda Ospedale San Paolo

Monza, Italy

Location

Azienda Ospedaliera San Gerardo

Monza, Italy

Location

Ospedale Civile S. Spirito AUSL

Pescara, Italy

Location

Unità Operativa Complessa di Malattie Infettive

Pescara, Italy

Location

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

Roma, Italy

Location

Comprensorio Ospedaliero Amedeo di Savoia

Torino, Italy

Location

Dipartimento di Malattie Infettive e Tropicali

Torino, Italy

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Costa Del Sol

Marbella, Spain

Location

Hospital Reg. Univ. Carlos Haya

Málaga, Spain

Location

Hospital Clínico Universitario de Valencia (Galindo)

Valencia, Spain

Location

Hospital General Universitario de Valencia (Abril)

Valencia, Spain

Location

Hospital Alvaro Cunqueiro

Vigo, Spain

Location

Mortimer Market Centre

London, United Kingdom

Location

Related Publications (1)

• 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

  BACKGROUND

MeSH Terms

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; abacavir, lamivudine drug combination

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2015
• First Posted: November 17, 2015
• Study Start: November 18, 2015
• Primary Completion: June 14, 2017
• Study Completion: January 24, 2018
• Last Updated: November 14, 2018
• Results First Posted: July 13, 2018

Record last verified: 2018-06

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

FR (11); IT (11); ES (10); US (12); GB (1); DE (4)