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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: TDF; Drug: E/C/F/TAF; Drug: FTC; Drug: FTC/TDF; Drug: 3TC; Drug: Third agent

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • CHU Saint-Pierre University Hospital
  • Ghent, Belgium
    • University Hospital Gent
• France
  • Bordeaux, France
    • CHU - Groupe Saint-Andre
  • Dijon, France
    • CHU de Dijon
  • Marseille, France
    • Hôpital Européen Marseille
  • Nantes, France
    • C.H.U. de Nantes
  • Nice, France
    • C.H.U. de NICE
  • Paris, France
    • CHU Hôtel Dieu
  • Paris, France
    • Hopital Necker les Enfants Malades
  • Paris cedex 10, France
    • Hopital Saint Louis
  • Paris cedex 12, France
    • Hopital Saint Antoine
  • Pessac, Cedex, France
    • Hôpital Haut-Lévêque
  • Tourcoing, France
    • Service des Maladies Infectieuses et du Voyageur
• Italy
  • Bergamo, Italy
    • Azienda Ospedaliera Papa Giovanni XXIII
  • Busto Arsizio, Italy
    • Busto Arsizio Hospital
  • Genova, Italy
    • IRCCS A.O.U. San Martino
  • Milano, Italy
    • Azienda Ospedaliera Luigi Sacco
  • Modena, Italy
    • Azienda Ospedaliero Universitaria Policlinico di Modena
  • Pescara, Italy
    • U.O. Malattie Infettive
  • Roma, Italy
    • Istituto Nazionale Malattie Infettive Lazzaro Spallanzani I.R.C.C.S.
  • Sassari, Italy
    • Azienda Ospedaliero Universitaria di Sassari
  • Torino, Italy
    • Dipartimento di Malattie Infettive e Tropicali
• Spain
  • Barcelona, Spain
    • Hospital Clínic de Barcelona
  • Barcelona, Spain
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Barcelona, Spain
    • Hospital Universitari Germans Trias i Pujol
  • Madrid, Spain
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain
    • Hospital 12 de Octubre
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Ramón y Cajal University Hospital
  • Marbella, Spain
    • Hospital Costa del Sol
  • Valencia, Spain
    • Hospital General Universitario de Valencia
• United Kingdom
  • Belfast, United Kingdom
    • Royal Victoria Hospital
  • London, United Kingdom
    • Mortimer Market Centre
  • Newcastle Upon Tyne, United Kingdom
    • Newcastle Royal Victoria Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: E/C/F/TAF; 150/150/200/10 mg FDC tablet administered orally once daily; Other Names: Genvoya®
Active Comparator: Remain current regimen; Participants will remain on current TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent.	Drug: TDF; 300 mg tablet administered orally once daily; Other Names: Viread®; Drug: FTC; 200 mg capsule administered orally once daily; Other Names: Emtriva®; Drug: FTC/TDF; 200/300 mg tablet administered orally once daily; Other Names: Truvada®; Drug: 3TC; Tablet administered orally; Other Names: Lamivudine; Epivir®; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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
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
Change From Baseline in CD4+ Cell Count at Week 24		Baseline; Week 24
Change in Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2015
• Primary Completion (Actual): February 21, 2018
• Study Completion (Actual): March 21, 2018

Study Registration Dates

• First Submitted: November 23, 2015
• First Submitted That Met QC Criteria: November 27, 2015
• First Posted (Estimate): November 30, 2015

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: February 18, 2020
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: HIV; HIV 1 Infection; Virologically-Suppressed
• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Lamivudine
• Other Study ID Numbers: GS-US-292-1826; 2015-002712-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No