Phase 3
Completed N=1,149
Study to Evaluate Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Regimen Versus Boosted Protease Inhibitor (bPI) Along With Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) Regimen in Virologically-Suppressed, HIV-1 Infected Participants
Human Immunodeficiency Virus Type 1
Source: ClinicalTrials.gov NCT02269917 ↗
Enrolled (actual)
1,149
Serious AEs
11.7%
Results posted
Nov 2018
Primary outcomePrimary: Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 48 — 2.5; 2.1 Percentage of participants — p=<0.001
◆ Published Evidence
Established
96citations · ~12 / year
Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial.
Summary
The purpose of this study is to demonstrate non-inferiority in efficacy while switching to a once-daily single-tablet regimen containing darunavir (DRV)/ cobicistat (COBI)/ emtricitabine (FTC)/ tenofovir alafenamide (TAF) (D/C/F/TAF tablet) relative to continuing the current regimen consisting of a boosted protease inhibitor (bPI) combined with tenofovir disoproxil fumarate (FTC/TDF) in virologically-suppressed (human immunodeficiency virus type 1 ribonucleic acid [HIV-1 RNA] concentrations less than [<] 50 copies per milliliter [copies/mL]) HIV-1 infected participants.
Linked Publications (5)
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Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial.
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Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials.
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Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-experienced, virologically suppressed patients with HIV-1: subgroup analyses of the phase 3 EMERALD study.
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Week 96 subgroup analyses of the phase 3, randomized AMBER and EMERALD trials evaluating the efficacy and safety of the once daily darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) single-tablet regimen in antiretroviral treatment (ART)-naïve and -experienced, virologically-suppressed adults living with HIV-1.
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Population Pharmacokinetic Analysis of Darunavir and Tenofovir Alafenamide in HIV-1-Infected Patients on the Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen (AMBER and EMERALD Studies).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 48 |
2.5; 2.1 | <0.001 sig |
| SECONDARY Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=20 Copies/mL) Cumulative Through 48 Weeks |
10.5; 11.4 | — |
| SECONDARY Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=200 Copies/mL) Cumulative Through 48 Weeks |
0.4; 0.0 | — |
| SECONDARY Percentage of Participants With Non-Virologic Rebound at Week 48 by Kaplan-Meier Estimates |
97.7; 97.8 | — |
| SECONDARY Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through Week 48 |
5.6; 6.3; 1.2; 1.9; 4.6; 4.8 | — |
| SECONDARY Change From Baseline in Serum Creatinine Levels at Weeks 24 and 48 |
1.22; 0.88; 1.27; 0.65 | =0.580 |
| SECONDARY Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Weeks 24 and 48 |
-0.38; 0.20; -0.94; -0.20 | =0.506 |
| SECONDARY Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 |
-1.67; -0.75; -1.97; -0.88 | =0.143 |
| SECONDARY Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst, by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) at Weeks 24 and 48 |
0.21; -0.93; -0.42; -1.76 | =0.054 |
| SECONDARY Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 |
6.20; 7.14; -0.78; 0.44; -0.76; 0.40 | <0.001 sig |
| SECONDARY Change From Baseline in Urine Retinol Binding Protein to Creatinine Ratio (URBPCR) and Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Weeks 24 and 48 |
126.19; 137.16; -30.27; 7.76; -27.09; 19.66 | <0.001 sig |
| SECONDARY Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Weeks 24 and 48 |
3.58; 8.55; 8.42; 8.57 | =0.288 |
| SECONDARY Percentage of Participants With Virologic Response Based on HIV-1 RNA Less Than (<)20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Food and Drug Administration (FDA) Snapshot Approach |
89.8; 88.4; 94.9; 93.7; 95.0; 94.2 | — |
| SECONDARY Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 48 as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm |
86.0; 83.6; 93.7; 92.9; 95.4; 94.7 | — |
| SECONDARY Change From Baseline in Cluster of Differentiation 4 Plus (CD4+) Cell Count at Weeks 24 and 48 |
653.3; 641.7; 14.3; 8.5; 21.0; 9.1 | — |
| SECONDARY Percentage of Participants With Treatment Adherence of Greater Than (>)95 Percent (%) (Approach 1) Through Week 48 |
91.6; 85.3 | — |
| SECONDARY Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 48 |
82.7; 77.2 | — |
| SECONDARY Number of Participants With Resistance to Study Drug |
1; 3 | — |
| SECONDARY Predose (Trough) Plasma Concentration (C0h) of Darunavir |
1775.29; 1732.00; 1910.30; 1643.38; 2022.99; 1806.37 | — |
| SECONDARY Percent Change From Baseline in Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) Levels at Weeks 24 and 48 |
-22.971; -0.027; -26.752; -3.751; -16.772; 16.312 | — |
| SECONDARY Percent Change From Baseline in Parathyroid Hormone (PTH) at Weeks 24 and 48 |
-3.092; 12.034; -4.510; 9.436 | — |
| SECONDARY Percent Change From Baseline in 25-hydroxy Vitamin D at Weeks 24 and 48 |
-3.0; 4.2; 25.2; 24.9 | — |
| SECONDARY Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48 |
1.55; 0.18; 2.06; 0.01; 0.91; 0.00 | <0.001 sig |
| SECONDARY Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 |
-0.713; -0.467; 0.102; -0.033; 0.132; -0.063 | — |
| SECONDARY Percentage of Participants With Virologic Rebound (HIV-1 RNA >=20 Copies/mL) Cumulative Through Week 96 |
13.8; 8.8 | — |
| SECONDARY Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 96 |
3.1; 2.3 | — |
| SECONDARY Percentage of Participants With Virologic Rebound (HIV-1 RNA >=200 Copies/mL) Cumulative Through Week 96 |
0.5; 0.6 | — |
| SECONDARY Percentage of Participants With Non-Virologic Rebound at Week 96 by Kaplan-Meier Estimates |
96.7; 97.8 | — |
| SECONDARY Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach |
85.3; 89.8; 90.7; 93.8; 91.2; 95.5 | — |
| SECONDARY Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the TLOVR Algorithm |
79.6; 88.1; 89.6; 94.3; 91.7; 95.7 | — |
| SECONDARY Percentage of Participants With Virologic Failure Based on HIV-1 RNA >=20, >=50, and >=200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach |
6.8; 6.0; 1.2; 1.7; 0.3; 0 | — |
| SECONDARY Change From Reference in CD4+ Cell Count at Week 96 |
32.07; 13.07 | — |
| SECONDARY Number of Participants With Resistance to Study Drug Through Week 96 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Treatment Adherence of >95 (Approach 1) Through Week 96 |
91.6; 87.3 | — |
| SECONDARY Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 96 |
82.8; 80.9 | — |
| SECONDARY Percentage of Participants Experiencing Grade 3 and Grade 4 AEs, SAEs, and Premature Discontinuation Due to AEs Through Week 96 |
10.5; 6.3; 2.4; 1.1; 8.7; 6.0 | — |
| SECONDARY Change From Reference in Serum Creatinine Levels at Week 96 |
0.0; 0.0 | — |
| SECONDARY Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Week 96 |
-0.9; 0.0 | — |
| SECONDARY Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (by CKD-EPI) at Week 96 |
-1.3; -0.7 | — |
| SECONDARY Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (by CKD-EPI) at Week 96 |
-0.9; 1.0 | — |
| SECONDARY Change From Reference in UACR at Week 96 |
-0.63; -0.93 | — |
| SECONDARY Change From Reference in URBPCR at Week 96 |
-25.08; -39.07 | — |
| SECONDARY Change From Reference in UPCR at Week 96 |
-22.23; -12.81 | — |
| SECONDARY Change From Reference in UB2MGCR at Week 96 |
-68.22; -110.31 | — |
| SECONDARY Percent Change From Reference in FEPO4 at Week 96 |
4.15; -3.19 | — |
| SECONDARY Percent Change From Reference in Levels of Serum P1NP at Week 96 |
-19.899; -18.466 | — |
| SECONDARY Percent Change From Reference in Levels of Serum CTX at Week 96 |
-10.192; -21.755 | — |
| SECONDARY Percent Change From Reference in Levels of PTH at Week 96 |
-17.171; -20.466 | — |
| SECONDARY Percent Change From Reference in Levels of 25-OH Vitamin D at Week 96 |
24.6; -1.9 | — |
| SECONDARY Percent Change From Reference in Hip and Spine BMD at Week 96 |
0.0173; 0.0108; 0.0193; 0.0279 | — |
| SECONDARY Change From Reference in BMD T-score of Hip and Spine at Week 96 |
0.122; 0.077; 0.176; 0.255 | — |
| SECONDARY Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates |
100; 100; 99.4; 100; 98.0; 98.5 | — |
| SECONDARY Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates |
100; 100; 98.1; 98.5; 94.3; 95.4 | — |
| SECONDARY Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension |
97.8; 97.9; 98.4; 97.4; 99.6; 98.7 | — |
| SECONDARY CD4+ Cell Count Post-Week 96 to End of Extension |
706.4; 681.3; 707.6; 676.2; 713.3; 686.1 | — |
| SECONDARY Percentage of Participants With Treatment Adherence of >95% From Week 96 to End of Extension |
89.5; 89.4 | — |
| SECONDARY Percentage of Participants Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Post-Week 96 to End of Extension |
5.7; 5.0; 2.1; 1.5; 7.3; 7.7 | — |
Eligibility Criteria
Inclusion Criteria
- Currently being treated with a stable antiretroviral (ARV) regimen consisting of a boosted protease inhibitor (limited to darunavir [DRV] or atazanavir with low-dose ritonavir [rtv] or cobicistat [COBI], or lopinavir with rtv) combined with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) only, for at least 6 consecutive months preceding the Screening visit
- On-treatment plasma human immunodeficiency virus type 1 ribonucleic acid (HIV-1 RNA) concentrations less than ( =) 50 copies/mL after previously reaching viral suppression between 12 and 2 months prior to Screening is acceptable, provided a subsequent test prior to Screening was <50 copies/mL
- Absence of history of failure on DRV treatment and absence of DRV resistance-associated mutations (RAMs), if documented historical genotypes are available
- Normal electrocardiogram (ECG) at Screening (or if abnormal, determined by the Investigator to be not clinically significant)
Exclusion Criteria
- A new acquired immunodeficiency syndrome (AIDS) - defining condition diagnosed within the 30 days prior to Screening
- Proven or suspected acute hepatitis within 30 days prior to study entry
- Hepatitis C antibody positive; however, participants previously cured of hepatitis C virus (HCV) infection, with documented sustained virologic response, that is, undetectable HCV RNA 24 weeks after the last dose of HCV treatment, are allowed to participate
- Hepatitis B surface antigen (HBsAg) positive
- Participants with cirrhosis as diagnosed based on local practices
Data sourced from ClinicalTrials.gov (NCT02269917) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.