Safety and Efficacy of Switching From Regimens of ABC/3TC + a 3rd Agent to E/C/F/TAF Fixed-Dose Combination (FDC) in Virologically-Suppressed HIV 1 Infected Adults

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) relative to continuing on a baseline regimen consisting of abacavir/lamivudine (ABC/3TC) plus a 3rd antiretroviral agent in HIV-1 infected participants.

Official Title
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A Phase 3b, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Abacavir/Lamivudine (ABC/3TC) Plus a Third Antiretroviral Agent to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed HIV 1 Infected Adult Subjects

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: E/C/F/TAF
* Drug: ABC/3TC
* Drug: Third Antiretroviral Agent


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: HIV-infected adult participants who meet the following criteria will be given the option to participate in the study: Currently receiving ABC/3TC plus a third antiretroviral (ARV) agent for ≥ 6 consecutive months preceding the screening visit. For subjects with 3 or more ART regimens, a regimen history must be provided to the Sponsor for approval. Allowed third antiretroviral agents include LPV/r, ATV+RTV, ATV+COBI (or ATV/COBI FDC), DRV+RTV, DRV + COBI (or DRV/COBI FDC) FPV + RTV, SQV + RTV, ATV (no booster), EFV, RPV, NVP, ETR, RAL or DTG 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 < 50 copies/mL at screening visit Individuals will have no evidence of previous virologic failure on a PI+RTV or integrase strand transfer inhibitor-based regimen (with or without resistance to either class of ARV). All documented historical plasma genotype(s) must not show resistance to tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC), including, but not limited to the presence of reverse transcriptase resistance mutants K65R, K70E, M184V/I, or thymidine analog associated mutations (TAMs) (TAMs are: M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). If a historical genotype is not available or subject has 3 or more ART regimens, subject will have proviral genotype analysis prior to Day 1 to confirm absence of archived resistance to TDF or FTC. Adequate renal function defined as having an estimated glomerular filtration rate of ≥ 30 mL/min as calculated by Cockcroft-Gault (eGFR-CG) Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E/C/F/TAF<br>Participants will switch to E/C/F/TAF FDC and receive treatment for 48 weeks. | Drug: E/C/F/TAF<br>* 150/150/200/10 mg FDC tablets administered orally once daily<br>* Other names: Genvoya®;|
| Active Comparator: ABC/3TC+3rd Agent<br>Participants will maintain prior regimen of ABC/3TC plus a third antiretroviral agent for 24 weeks followed by a delayed switch to E/C/F/TAF FDC. Note: the prior regimen is determined by the participant's clinician (prior to entry into the study) and will consist of one of the third antiretroviral agents listed. | Drug: ABC/3TC<br>* 600/300 mg tablets administered orally once daily<br>* Other names: Kivexa;Drug: Third Antiretroviral Agent<br>* Third antiretroviral agents could include one of the following: ATV+cobicistat (COBI; Tybost®) or ATV/COBI FDC DRV+COBI or DRV/COBI FDC darunavir (DRV; Prezista®) + RTV lopinavir/ritonavir (LPV/r; Kaletra®) atazanavir (ATV; Reyataz®) + ritonavir (RTV; Norvir®) efavirenz (EFV; Sustiva®) etravirine (ETR; Intelence®) nevirapine (NVP; Viramune®) rilpivirine (RPV; Edurant®) dolutegravir (DTG; Tivicay®) raltegravir (RAL; Isentress®) fosamprenavir (FPV; Lexiva®) + RTV saquinavir (SQV; Invirase®) + RTV ATV (no booster) 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 24 | The percentage of participants achieving 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 12 | The percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 12 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 12 | 
| Percentage of Participants Who Have HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Algorithm at Week 48 | The percentage of participants achieving 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 From Baseline in CD4+ Cell Count at Week 48 |  | Baseline; Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Virologically-Suppressed, Antiretroviral agents, HIV 1 Infection