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

NCT ID: NCT02616783

Last Updated: 2020-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 167 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-22
• Study Completion Date: 2018-03-21

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.

Conditions

HIV-1 Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

E/C/F/TAF

Participants will switch from tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or 3TC plus a third agent to E/C/F/TAF and will receive treatment for 48 weeks.

Group Type: EXPERIMENTAL

E/C/F/TAF

Intervention Type: DRUG

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

Remain current regimen

Participants will remain on current TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent.

Group Type: ACTIVE_COMPARATOR

TDF

Intervention Type: DRUG

300 mg tablet administered orally once daily

FTC

Intervention Type: DRUG

200 mg capsule administered orally once daily

FTC/TDF

Intervention Type: DRUG

200/300 mg tablet administered orally once daily

3TC

Intervention Type: DRUG

Tablet administered orally

Third agent

Intervention Type: DRUG

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

Interventions

E/C/F/TAF

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

Intervention Type: DRUG

TDF

300 mg tablet administered orally once daily

Intervention Type: DRUG

FTC

200 mg capsule administered orally once daily

Intervention Type: DRUG

FTC/TDF

200/300 mg tablet administered orally once daily

Intervention Type: DRUG

3TC

Tablet administered orally

Intervention Type: DRUG

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

Intervention Type: DRUG

Other Intervention Names

Genvoya®; Viread®; Emtriva®; Truvada®; Lamivudine; Epivir®

Eligibility Criteria

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

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

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

CHU Saint-Pierre University Hospital

Brussels, , Belgium

University Hospital Gent

Ghent, , Belgium

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 Antoine

Paris, , France

Hopital Saint Louis

Paris, , France

Hopital Haut-Leveque

Pessac, , France

Service des Maladies Infectieuses et du Voyageur

Tourcoing, , France

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

Milan, , 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, , Italy

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, , Spain

Royal Victoria Hospital

Belfast, , United Kingdom

Mortimer Market Centre

London, , United Kingdom

Newcastle Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

Countries

Belgium; France; Italy; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 31578954 (View on PubMed)

Provided Documents

Document Type: Study Protocol: Original

View Document

Document Type: Study Protocol: Amendment 1

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-002712-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-292-1826

Identifier Type: -

Identifier Source: org_study_id