Clinical trial NCT02616783: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Keywords: HIV 1 Infection
HIV
Virologically-Suppressed
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-11-30
Enrollment: 167
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline to Week 48 in Spine BMD
timeFrame: Baseline; Week 48
measure: Percent Change From Baseline to Week 48 in Hip BMD
timeFrame: Baseline; Week 48
Secondary outcomes:
measure: Percent Change From Baseline to Week 24 in Spine BMD
timeFrame: Baseline; Week 24
measure: Percent Change From Baseline to Week 24 in Hip BMD
timeFrame: Baseline; Week 24
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 24
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 24
timeFrame: Baseline; Week 24
measure: Change in Baseline in CD4+ Cell Count at Week 48
timeFrame: Baseline; Week 48
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: CHU Saint-Pierre University Hospital
city: Ghent
country: Belgium
facility: University Hospital Gent
city: Bordeaux
country: France
facility: CHU - Groupe Saint-Andre
city: Dijon
country: France
facility: CHU de Dijon
city: Marseille
country: France
facility: Hopital Europeen Marseille
city: Nantes
country: France
facility: C.H.U. de Nantes
city: Nice
country: France
facility: C.H.U. de NICE
city: Paris cedex 10
country: France
facility: Hopital Saint Louis
city: Paris cedex 12
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: CHU Hotel Dieu
city: Paris
country: France
facility: Hopital Necker les Enfants Malades
city: Pessac, Cedex
country: France
facility: Hopital Haut-Leveque
city: Tourcoing
country: France
facility: Service des Maladies Infectieuses et du Voyageur
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Busto Arsizio
country: Italy
facility: Busto Arsizio Hospital
city: Genova
country: Italy
facility: IRCCS A.O.U. San Martino
city: Milano
country: Italy
facility: Azienda Ospedaliera Luigi Sacco
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico di Modena
city: Pescara
country: Italy
facility: U.O. Malattie Infettive
city: Roma
country: Italy
facility: Istituto Nazionale Malattie Infettive Lazzaro Spallanzani I.R.C.C.S.
city: Sassari
country: Italy
facility: Azienda Ospedaliero Universitaria di Sassari
city: Torino
country: Italy
facility: Dipartimento di Malattie Infettive e Tropicali
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Ramon Y Cajal University Hospital
city: Marbella
country: Spain
facility: Hospital Costa Del Sol
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Belfast
country: United Kingdom
facility: Royal Victoria Hospital
city: London
country: United Kingdom
facility: Mortimer Market Centre
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle Royal Victoria Infirmary
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Maggiolo F, Rizzardini G, Raffi F, Pulido F, Mateo-Garcia MG, Molina JM, Ong E, Shao Y, Piontkowsky D, Das M, McNicholl I, Haubrich R. Bone mineral density in virologically suppressed people aged 60 years or older with HIV-1 switching from a regimen containing tenofovir disoproxil fumarate to an elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide single-tablet regimen: a multicentre, open-label, phase 3b, randomised trial. Lancet HIV. 2019 Oct;6(10):e655-e666. doi: 10.1016/S2352-3018(19)30195-X.