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

NCT02616783 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: GS-US-292-18262015-002712-32
• Study Type: interventional
• Target: 167
• Locations: 5 countries
• Sites: 35

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

Keywords

HIV 1 Infection; HIV; Virologically-Suppressed

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline to Week 48 in Spine BMD

  Baseline; Week 48

• Percent Change From Baseline to Week 48 in Hip BMD

  Baseline; Week 48

Secondary Outcomes (6)

• Percent Change From Baseline to Week 24 in Spine BMD

  Baseline; Week 24

• Percent Change From Baseline to Week 24 in Hip BMD

  Baseline; Week 24

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm

  Week 24

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

  Week 48

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

  Baseline; Week 24

Study Arms (2)

E/C/F/TAF

EXPERIMENTAL

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.

Drug: E/C/F/TAF

Remain current regimen

ACTIVE COMPARATOR

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

Drug: TDF; Drug: FTC; Drug: FTC/TDF; Drug: 3TC; Drug: Third agent

Interventions

E/C/F/TAF DRUG

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

Also known as: Genvoya®

E/C/F/TAF

TDF DRUG

300 mg tablet administered orally once daily

Also known as: Viread®

Remain current regimen

FTC DRUG

200 mg capsule administered orally once daily

Also known as: Emtriva®

Remain current regimen

FTC/TDF DRUG

200/300 mg tablet administered orally once daily

Also known as: Truvada®

Remain current regimen

3TC DRUG

Tablet administered orally

Also known as: Lamivudine, Epivir®

Remain current regimen

Third agent 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

Remain current regimen

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (35)

CHU Saint-Pierre University Hospital

Brussels, Belgium

Location

University Hospital Gent

Ghent, Belgium

Location

CHU - Groupe Saint-Andre

Bordeaux, France

Location

CHU de Dijon

Dijon, 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 Necker les Enfants Malades

Paris, France

Location

Hopital Saint Antoine

Paris, France

Location

Hopital Saint Louis

Paris, France

Location

Hopital Haut-Leveque

Pessac, France

Location

Service des Maladies Infectieuses et du Voyageur

Tourcoing, France

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, Italy

Location

Busto Arsizio Hospital

Busto Arsizio, Italy

Location

IRCCS A.O.U. San Martino

Genova, Italy

Location

Azienda Ospedaliera Luigi Sacco

Milan, Italy

Location

Azienda Ospedaliero Universitaria Policlinico di Modena

Modena, Italy

Location

U.O. Malattie Infettive

Pescara, Italy

Location

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

Roma, Italy

Location

Azienda Ospedaliero Universitaria di Sassari

Sassari, 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 Germans Trias i Pujol

Barcelona, Spain

Location

Hospital Vall d'Hebron

Barcelona, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Ramon Y Cajal University Hospital

Madrid, Spain

Location

Hospital Costa Del Sol

Marbella, Spain

Location

Hospital General Universitario de Valencia

Valencia, Spain

Location

Royal Victoria Hospital

Belfast, United Kingdom

Location

Mortimer Market Centre

London, United Kingdom

Location

Newcastle Royal Victoria Infirmary

Newcastle upon Tyne, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31578954 DERIVED

MeSH Terms

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Lamivudine

Intervention Hierarchy (Ancestors)

Cobicistat; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 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; Zalcitabine; Dideoxynucleosides

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 23, 2015
• First Posted: November 30, 2015
• Study Start: December 22, 2015
• Primary Completion: February 21, 2018
• Study Completion: March 21, 2018
• Last Updated: March 4, 2020
• Results First Posted: February 19, 2019

Record last verified: 2019-01

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

GB (3); BE (2); FR (11); IT (9); ES (10)