Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
E/C/F/TDF · 3 trials · 2 indications
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 of the double-blind phase 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 eGFR-CG equation at Week 24 was analyzed in Cohort 1 (treatment-naive).
Change from baseline in eGFR-CG equation at Week 24 was analyzed in Cohort 2 (treatment-experienced).
Change from baseline in eGFR-MDRD equation at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m\^2 body surface area.
Change from baseline in eGFR-MDRD equation at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m\^2 body surface area.
Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m\^2 body surface area.
Change from baseline in eGFR-CKD-EPI based on cystatin C equation (not adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m\^2 body surface area.
Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 1 (treatment-naive). The calculation was normalized to 1.73 m\^2 body surface area.
Change from baseline in eGFR-CKD-EPI based on cystatin C equation (adjusted for age, sex, and race) at Week 24 was analyzed in Cohort 2 (treatment-experienced). The calculation was normalized to 1.73 m\^2 body surface area.
Change from baseline in aGFR at Weeks 2, 4, and 24 was analyzed in Cohort 1 (treatment-naive). aGFR was calculated using iohexol plasma clearance.
Change from baseline in aGFR at Weeks 2, 4, and 24 was analyzed in Cohort 2 (treatment-experienced). aGFR was calculated using iohexol plasma clearance.
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed in Cohort 1 (treatment-naive) using the FDA snapshot analysis algorithm.
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed in Cohort 2 (treatment-experienced) using the FDA snapshot analysis algorithm.
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a patient'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.
| Arm | Type | Description |
|---|---|---|
| E/C/F/TDF | EXPERIMENTAL | E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo |
| ATV + RTV+ FTC/TDF | ACTIVE_COMPARATOR | ATV + RTV + FTC/TDF + E/C/F/TDF placebo |
| Open-Label Extension Phase | EXPERIMENTAL | After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF. |
| E/C/F/TDF (Cohort 1) | EXPERIMENTAL | Participants who have not received prior antiretroviral (ARV) treatment and who are virologically unsuppressed at baseline will initiate treatment with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) single-tablet regimen (STR) for up to 96 weeks. Following Week 96, participants continued their treatment until all participants discontinued from the study or commercial approval of E/C/F/TDF was received in the applicable country. |
| COBI+PI+2 NRTI (Cohort 2) | EXPERIMENTAL | Participants who have received prior ARV treatment and who are virologically suppressed at baseline will continue their treatment regimen, switching the regimen's pharmacoenhancer component from ritonavir to cobicistat (COBI), and continuing their existing protease inhibitor (PI; either atazanavir (ATV) or darunavir (DRV)) plus 2 nucleoside reverse transcriptase inhibitor (NRTI) regimen for up to 96 weeks. Following Week 96, participants continued their treatment until all participants discontinued from the study or commercial approval of cobicistat was received in the applicable country. |
| E/C/F/TAF | EXPERIMENTAL | E/C/F/TAF plus E/C/F/TDF placebo for at least 48 weeks |
| E/C/F/TAF Open-Label | EXPERIMENTAL | Following study unblinding, participants from the E/C/F/TAF and E/C/F/TDF arms may have the option to receive E/C/F/TAF during an open-label extension phase. Also, participants who are actively participating in a Gilead-sponsored study of cobicistat-boosted darunavir plus nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) who have reached the protocol-defined secondary endpoint (Week 48) and remain virologically suppressed are eligible to participate and receive E/C/F/TAF in this open-label extension phase. |
| Name | Type | Description |
|---|---|---|
| E/C/F/TDF | DRUG | 150/150/200/300 mg FDC tablet administered orally with food once daily |
| ATV | DRUG | 300 mg capsule administered orally with food once daily |
| RTV | DRUG | 100 mg tablet administered orally with food once daily |
| FTC/TDF | DRUG | 200/300 mg tablet administered orally with food once daily |
| E/C/F/TDF Placebo | DRUG | Tablet administered orally with food once daily |
| ATV Placebo | DRUG | Tablet administered orally with food once daily |
| RTV Placebo | DRUG | Capsule administered orally with food once daily |
| FTC/TDF Placebo | DRUG | Tablet administered orally with food once daily |
| E/C/F/TAF | DRUG | 150/150/200/10 mg FDC tablet administered orally with food once daily |
| COBI | DRUG | COBI 150 mg tablet administered with food orally once daily |
| DRV | DRUG | DRV 800 mg tablet administered orally once daily |
| NRTI | DRUG | Participants will receive 2 investigator-selected NRTIs, which may include abacavir (ABC), lamivudine (3TC)/zidovudine (ZDV), didanosine (DDI), emtricitabine (FTC), ABC/3TC, 3TC, tenofovir disoproxil fumarate (TDF), or FTC/TDF, administered according to prescribing information. |
| E/C/F/TAF Placebo | DRUG | Tablet administered orally once daily |
Key Inclusion Criteria: * Female (at birth), age ≥ 18 years * Ability to understand and sign a written informed consent form * Plasma HIV-1 RNA levels ≥ 500 copies/mL * No prior use of any approved or investigational antiretroviral drug for any length of time * Screening genotype report must show s...
E/C/F/TAF is an investigational single-tablet regimen being developed for the treatment of HIV-1 infection, including HIV-1 positive patients who are antiretroviral treatment-naive or virologically suppressed. It is also studied in patients with mild to moderate renal impairment and in pediatric populations, including adolescents and children.
E/C/F/TAF is a combination of four antiretroviral agents: elvitegravir, an integrase inhibitor; cobicistat, a pharmacokinetic enhancer; emtricitabine, a nucleoside reverse transcriptase inhibitor; and tenofovir alafenamide, a nucleotide reverse transcriptase inhibitor. Together, they target multiple steps in the HIV-1 replication cycle.
E/C/F/TAF is developed by Gilead Sciences, Inc., a biopharmaceutical company traded on NASDAQ under the ticker GILD. Gilead is conducting clinical trials to evaluate the safety and efficacy of this combination regimen in various HIV-1 infected populations.
E/C/F/TAF is in Phase 2 clinical development. While some completed trials are Phase 3, the overall development program includes Phase 2 studies in adolescents and children. The drug has received FDA designations of Priority Review and Accelerated Approval, but it remains investigational and is not yet approved.
E/C/F/TAF has been studied in six completed clinical trials with a total enrollment of 3,578 participants. Key trials include NCT01780506, a Phase 3 study in treatment-naive adults; NCT01818596, a Phase 3 study in patients with renal impairment; and NCT01854775 and NCT02276612, Phase 2 studies in pediatric populations.
Yes, E/C/F/TAF is the same as Genvoya. The acronym stands for elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide, which are the four components of the single-tablet regimen. Clinical trial titles refer to it as Genvoya, and it is being evaluated for HIV-1 treatment.