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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

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ClinicalTrials.gov Identifier: NCT02616783
Recruitment Status : Completed
First Posted : November 30, 2015
Results First Posted : February 19, 2019
Last Update Posted : March 4, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE November 23, 2015
First Posted Date  ICMJE November 30, 2015
Results First Submitted Date  ICMJE January 31, 2019
Results First Posted Date  ICMJE February 19, 2019
Last Update Posted Date March 4, 2020
Actual Study Start Date  ICMJE December 22, 2015
Actual Primary Completion Date February 21, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2019)
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 27, 2015)
Percent change from baseline to Week 48 in spine and hip bone mineral density (BMD) [ Time Frame: Baseline; Week 48 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2019)
  • 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 ]
    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.
  • 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 ]
    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.
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 27, 2015)
  • Percent change from baseline to Week 24 in spine and hip BMD [ Time Frame: Baseline; Week 24 ]
  • Proportion of participants with HIV-1 RNA < 50 copies/mL at Weeks 24 and 48 as defined by the Food and Drug Administration (FDA) snapshot algorithm [ Time Frame: Week 24 and 48 ]
  • Change in CD4+ cell count from baseline at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV-1 Infection
Intervention  ICMJE
  • Drug: E/C/F/TAF
    150/150/200/10 mg FDC tablet administered orally once daily
    Other Name: Genvoya®
  • Drug: TDF
    300 mg tablet administered orally once daily
    Other Name: Viread®
  • Drug: FTC
    200 mg capsule administered orally once daily
    Other Name: Emtriva®
  • Drug: FTC/TDF
    200/300 mg tablet administered orally once daily
    Other Name: 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: E/C/F/TAF
  • Active Comparator: Remain current regimen
    Participants will remain on current TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent.
    Interventions:
    • Drug: TDF
    • Drug: FTC
    • Drug: FTC/TDF
    • Drug: 3TC
    • Drug: Third agent
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 31, 2019)
167
Original Estimated Enrollment  ICMJE
 (submitted: November 27, 2015)
150
Actual Study Completion Date  ICMJE March 21, 2018
Actual Primary Completion Date February 21, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Italy,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02616783
Other Study ID Numbers  ICMJE GS-US-292-1826
2015-002712-32 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP