Switching From a Tenofovir Disoproxil Fumarate (TDF) Containing Regimen to Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide (E/C/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed, HIV-1 Infected Adults Aged ≥ 60 Years

HIV-1 Infection Clinical Trial

Official title:

A Phase 3b, Randomized, Open-Label Study to Evaluate Switching From a Tenofovir Disoproxil Fumarate (TDF) Containing Regimen to Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide (E/C/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed, HIV-1 Infected Subjects Aged ≥ 60 Years

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02616783
• Other study ID #: GS-US-292-1826
• Secondary ID: 2015-002712-32
• Status: Completed
• Phase: Phase 3
• Start date: December 22, 2015
• Est. completion date: March 21, 2018

Study information

• Verified date: January 2019
• 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 safety of elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (E/C/F/TAF) relative to unchanged current antiretroviral therapy (ART) by assessing spine and hip bone mineral density (BMD) measured at Week 48 in virologically-suppressed, HIV-1 infected participants aged ≥ 60 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 167
• Est. completion date: March 21, 2018
• Est. primary completion date: February 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Key Inclusion Criteria:

• Currently receiving a TDF and FTC or 3TC-containing 'backbone' (maximum 2 NRTIs) regimen plus a third agent for = 6 consecutive months prior to screening visit. For individuals with 3 or more ART regimens, a regimen history must be provided for approval by the Sponsor.

Refer to assigned interventions for allowed third agents of the current regimen.

• 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 level < 50 copies/mL at screening visit

• Adequate renal function

• Estimated glomerular filtration rate = 30 mL/min according to the Cockcroft-Gault formula (eGFRCG) and are on ARVs that are appropriately dose adjusted for renal function per package insert

• All documented historical plasma genotype(s) must not show resistance to TDF or FTC, including, but not limited to the presence of reverse transcriptase resistance mutations K65R, K70E, M184V/I, or thymidine analog-associated mutations (TAMs) that include M41L, L210W, D67N, K70R, T215Y/F, K219Q/E/N/R. If historical plasma prior to first ART is not available or individual has 3 or more ART regimens, individuals will have proviral genotype analysis prior to Day 1 to confirm absence of archived resistance to TDF or FTC.

• Study performed dual energy x-ray absorptiometry (DXA) scan and T-score received prior to Day 1

Key Exclusion Criteria:

• Previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) (for any length of time) if the current regimen contains a PI/r

• Individuals will have no evidence of previous virologic failure on a PI/r or INSTI-based regimen (with or without resistance to either class of ARV)

• A new AIDS-defining condition diagnosed within the 30 days prior to screening (except CD4+ cell count and/or percentage criteria)

• Hepatitis C virus that would require therapy during the study

• Individuals receiving ongoing treatment for bone disease (eg, osteoporosis), including bisphosphonates, denosumab, and strontium ranelate

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

Related Conditions & MeSH terms

• HIV-1 Infection
• Infection

Intervention

Drug:
• E/C/F/TAF
150/150/200/10 mg FDC tablet administered orally once daily
• TDF
300 mg tablet administered orally once daily
• FTC
200 mg capsule administered orally once daily
• FTC/TDF
200/300 mg tablet administered orally once daily
• 3TC
Tablet administered orally
• Third agent
Third agent may include one of the following regimens: lopinavir+ritonavir (LPV/r; Kaletra®), atazanavir (ATV; Reyataz®) + ritonavir (RTV; Norvir®), ATV + cobicistat (COBI;Tybost®) (or ATV/COBI FDC), DRV + RTV, darunavir (DRV; Prezista®) + COBI (or DRV/COBI FDC), fosamprenavir (FPV; Lexiva®) + RTV , saquinavir (SQV; Invirase®; Fortovase®) + RTV, efavirenz (EFV;Sustiva®), rilpivirine (RPV;Edurant®), nevirapine (NVP;Viramune®), etravirine (ETR;Intelence®), raltegravir (RAL; Isentress®), elvitegravir (EVG) + COBI, or dolutegravir (DTG;Tivicay®) 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
Belgium	CHU Saint-Pierre University Hospital	Brussels
Belgium	University Hospital Gent	Ghent
France	CHU - Groupe Saint-Andre	Bordeaux
France	CHU de Dijon	Dijon
France	Hopital Europeen Marseille	Marseille
France	C.H.U. de Nantes	Nantes
France	C.H.U. de NICE	Nice
France	CHU Hotel Dieu	Paris
France	Hopital Necker les Enfants Malades	Paris
France	Hopital Saint Louis	Paris cedex 10
France	Hopital Saint Antoine	Paris cedex 12
France	Hopital Haut-Leveque	Pessac, Cedex
France	Service des Maladies Infectieuses et du Voyageur	Tourcoing
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	Busto Arsizio Hospital	Busto Arsizio
Italy	IRCCS A.O.U. San Martino	Genova
Italy	Azienda Ospedaliera Luigi Sacco	Milano
Italy	Azienda Ospedaliero Universitaria Policlinico di Modena	Modena
Italy	U.O. Malattie Infettive	Pescara
Italy	Istituto Nazionale Malattie Infettive Lazzaro Spallanzani I.R.C.C.S.	Roma
Italy	Azienda Ospedaliero Universitaria di Sassari	Sassari
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 Germans Trias i Pujol	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Ramon Y Cajal University Hospital	Madrid
Spain	Hospital Costa Del Sol	Marbella
Spain	Hospital General Universitario de Valencia	Valencia
United Kingdom	Royal Victoria Hospital	Belfast
United Kingdom	Mortimer Market Centre	London
United Kingdom	Newcastle Royal Victoria Infirmary	Newcastle Upon Tyne

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

Belgium,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline to Week 48 in Spine BMD		Baseline; Week 48
Primary	Percent Change From Baseline to Week 48 in Hip BMD		Baseline; Week 48
Secondary	Percent Change From Baseline to Week 24 in Spine BMD		Baseline; Week 24
Secondary	Percent Change From Baseline to Week 24 in Hip BMD		Baseline; Week 24
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm	The percentage of participants with 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 With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm	The percentage of participants with 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 in Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48