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

HIV-1 Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02605954
• Other study ID #: GS-US-292-1823
• Secondary ID: 2015-002711-15
• Status: Completed
• Phase: Phase 3
• Start date: November 18, 2015
• Est. completion date: January 24, 2018

Study information

• Verified date: June 2018
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 275
• Est. completion date: January 24, 2018
• Est. primary completion date: June 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• E/C/F/TAF
150/150/200/10 mg FDC tablets administered orally once daily
• ABC/3TC
600/300 mg tablets administered orally once daily
• 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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Spain,  United Kingdom, 

References & 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Change From Baseline in CD4+ Cell Count at Week 24		Baseline; Week 24
Secondary	Change From Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48