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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 21, 2018

Interventions

  • Drug: E/C/F/TAF
    • 150/150/200/10 mg FDC tablet administered orally once daily
  • Drug: TDF
    • 300 mg tablet administered orally once daily
  • Drug: FTC
    • 200 mg capsule administered orally once daily
  • Drug: FTC/TDF
    • 200/300 mg tablet administered orally once daily
  • Drug: 3TC
    • Tablet administered orally
  • 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

Arms, Groups and Cohorts

  • 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.
  • Active Comparator: Remain current regimen
    • Participants will remain on current TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent.

Clinical Trial Outcome Measures

Primary Measures

  • 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

Secondary Measures

  • 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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 60 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Gilead Sciences
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Gilead Study Director, Study Director, Gilead Sciences

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