HIV-1 InfectionPhase 3NCT02616783
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 3 study testing E/C/F/TAF, TDF and FTC in people with HIV-1 Infection, run by Gilead Sciences at 35 sites in 5 countries.
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… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- E/C/F/TAF, TDF and FTC
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 167 participants
- Where
- 35 sitesin 5 countries
- Study dates
- 22 Dec 2015to 21 Mar 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
35 sites in 5 countries.
35 sites in 5 countries
France11 sites
CHU - Groupe Saint-Andre
Bordeaux
CHU de Dijon
Dijon
Hopital Europeen Marseille
Marseille
C.H.U. de Nantes
Nantes
C.H.U. de NICE
Nice
CHU Hotel Dieu
Paris
Hopital Necker les Enfants Malades
Paris
Hopital Saint Antoine
Paris
Hopital Saint Louis
Paris
Hopital Haut-Leveque
Pessac
Service des Maladies Infectieuses et du Voyageur
Tourcoing
Spain10 sites
Hospital Clinic de Barcelona
Barcelona
Hospital de la Santa Creu i Sant Pau
Barcelona
Hospital Universitari Germans Trias i Pujol
Barcelona
Hospital Vall d'Hebron
Barcelona
Hospital 12 de Octubre
Madrid
Hospital General Universitario Gregorio Maranon
Madrid
Hospital Universitario La Paz
Madrid
Ramon Y Cajal University Hospital
Madrid
Hospital Costa Del Sol
Marbella
Hospital General Universitario de Valencia
Valencia
Italy9 sites
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo
Busto Arsizio Hospital
Busto Arsizio
IRCCS A.O.U. San Martino
Genova
Azienda Ospedaliera Luigi Sacco
Milan
Azienda Ospedaliero Universitaria Policlinico di Modena
Modena
U.O. Malattie Infettive
Pescara
Istituto Nazionale Malattie Infettive Lazzaro Spallanzani I.R.C.C.S.
Roma
Azienda Ospedaliero Universitaria di Sassari
Sassari
Dipartimento di Malattie Infettive e Tropicali
Torino
United Kingdom3 sites
Royal Victoria Hospital
Belfast
Mortimer Market Centre
London
Newcastle Royal Victoria Infirmary
Newcastle upon Tyne
Belgium2 sites
CHU Saint-Pierre University Hospital
Brussels
University Hospital Gent
Ghent
About this study
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
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
- Being tested
- E/C/F/TAF, TDF, FTC, FTC/TDF, 3TC
- Keywords
- HIV 1 Infection, HIV, Virologically-Suppressed
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E/C/F/TAFDrug
Also called Genvoya®
150/150/200/10 mg FDC tablet administered orally once daily
TDFDrug
Also called Viread®
300 mg tablet administered orally once daily
FTCDrug
Also called Emtriva®
200 mg capsule administered orally once daily
FTC/TDFDrug
Also called Truvada®
200/300 mg tablet administered orally once daily
3TCDrug
Also called Lamivudine, Epivir®
Tablet administered orally
Third agentDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: TDF; Drug: FTC; Drug: FTC/TDF; Drug: 3TC; Drug: Third agent |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline to Week 48 in Spine BMD
Measured: Baseline; Week 48
Percent Change From Baseline to Week 48 in Hip BMD
Measured: Baseline; Week 48
Secondary outcomes (6)
Percent Change From Baseline to Week 24 in Spine BMD
Measured: Baseline; Week 24
Percent Change From Baseline to Week 24 in Hip BMD
Measured: 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.
Measured: 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.
Measured: Week 48
Change From Baseline in CD4+ Cell Count at Week 24
Measured: Baseline; Week 24
Change in Baseline in CD4+ Cell Count at Week 48
Measured: Baseline; Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2015 (estimated)
- Study start22 Dec 2015
- Primary completion21 Feb 2018
- Study completion21 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1 InfectionStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 167 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02616783
- Sponsor's protocol ID
- GS-US-292-1826
- Other IDs
- 2015-002712-32, 2015
- Status last verified
- Jan 2019
- First submitted
- 23 Nov 2015
- Last updated
- 4 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
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.
PubMed 31578954
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02616783
- Acronym / sponsor ID
- GS-US-292-1826
- Conditions
- HIV-1 Infection
- Keywords
- HIV 1 Infection, HIV, Virologically-Suppressed
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 167 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 22 Dec 2015 (actual)
- Primary completion
- 21 Feb 2018 (actual)
- Study completion
- 21 Mar 2018 (actual)
- First posted
- 30 Nov 2015 (estimated)
- Results
- Posted 19 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| E/C/F/TAF | Experimental | Drug: E/C/F/TAFParticipants 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. |
| Remain current regimen | Active comparator | Drug: TDF, Drug: FTC, Drug: FTC/TDF, Drug: 3TC, Drug: Third agentParticipants will remain on current TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E/C/F/TAFAlso: Genvoya®150/150/200/10 mg FDC tablet administered orally once daily | Drug | E/C/F/TAF |
| TDFAlso: Viread®300 mg tablet administered orally once daily | Drug | Remain current regimen |
| FTCAlso: Emtriva®200 mg capsule administered orally once daily | Drug | Remain current regimen |
| FTC/TDFAlso: Truvada®200/300 mg tablet administered orally once daily | Drug | Remain current regimen |
| 3TCAlso: Lamivudine, Epivir®Tablet administered orally | Drug | Remain current regimen |
| Third agentThird 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 | Drug | Remain current regimen |
Primary outcome
Percent Change From Baseline to Week 48 in Spine BMD
Time frame: Baseline; Week 48
Percent Change From Baseline to Week 48 in Hip BMD
Time frame: Baseline; Week 48
6 secondary outcomes
Percent Change From Baseline to Week 24 in Spine BMD
Time frame: Baseline; Week 24
Percent Change From Baseline to Week 24 in Hip BMD
Time frame: 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
Time frame: Week 24
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
Time frame: Week 48
Change From Baseline in CD4+ Cell Count at Week 24
Time frame: Baseline; Week 24
Change in Baseline in CD4+ Cell Count at Week 48
Time frame: Baseline; Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31578954Maggiolo 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
35 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing E/C/F/TAF, TDF and FTC in people with HIV-1 Infection, run by Gilead Sciences at 35 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in France, Spain, Italy, United Kingdom, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline to Week 48 in Spine BMD (time frame: Baseline; Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02616783, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2020.