A Study to Evaluate Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Fixed Dose Combination (FDC) Versus a Regimen Consisting of Darunavir/Cobicistat FDC With Emtricitabine/Tenofovir Disoproxil Fumarate FDC in Treatment-naive HIV Type 1 Infected Subjects

A Phase 3, Randomized, Active-controlled, Double-blind Study to Evaluate Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Once Daily Fixed Dose Combination Regimen Versus a Regimen Consisting of Darunavir/Cobicistat Fixed Dose Combination Coadministered With Emtricitabine/Tenofovir Disoproxil Fumarate Fixed Dose Combination in Antiretroviral Treatment-naive Human Immunodeficiency Virus Type 1 Infected Subjects

The purpose of this study is to demonstrate non-inferiority in efficacy of a darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed dose combination (FDC) tablet versus Darunavir/Cobicistat (DRV/COBI) FDC coadministered with Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) FDC in human immunodeficiency virus-1 (HIV-1) infected, antiretroviral (ARV) treatment naive adult participants.

Study Overview

• Status: Completed
• Conditions: Immunodeficiency Virus Type 1, Human
• Intervention / Treatment: Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC; Drug: FTC/TDF FDC Matching Placebo; Drug: DRV/COBI FDC Matching Placebo; Drug: DRV/COBI FDC; Drug: FTC/TDF FDC; Drug: D/C/F/TAF FDC - Matching Placebo

Detailed Description

This is a Phase 3, multicenter (when more than one hospital or medical school team work on a medical research study), randomized (study drug assigned by chance), double-blind (a medical research study in which neither the researchers nor the participant know what treatment the participant is receiving), active-controlled (study in which the experimental treatment or procedure is compared to a standard [control] treatment or procedure) study. The study consists of 5 periods: a Screening period, Double-blind treatment period, Single-arm treatment period, Extension period and a Follow-up period. Participants will receive either darunavir (DRV)/ cobicistat (COBI)/emtricitabine (FTC) /tenofovir alafenamide (TAF) fixed dose combination (D/C/F/TAF FDC) or DRV/COBI FDC along with FTC/TDF FDC. Primarily percentage of participants with human immunodeficiency virus (HIV) -1 Ribonucleic acid (RNA) less than (<) 50 copies per milliliter (copies/ml) defined by snapshot analysis will be evaluated. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 725
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium
  • Brussel, Belgium
  • Brussels, Belgium
  • Gent, Belgium
• Canada
  • Ontario
    • Toronto, Ontario, Canada
  • Quebec
    • Montreal, Quebec, Canada
• France
  • Clamart, France
  • Le Kremlin Bicetre, France
  • Lyon, France
  • Marseille, France
  • Montpellier, France
  • Nantes, France
  • Paris, France
  • Strasbourg, France
  • Tourcoing, France
• Germany
  • Berlin, Germany
  • Bonn, Germany
  • Essen, Germany
  • Frankfurt, Germany
  • Freiburg im Breisgau, Germany
  • Hamburg, Germany
  • Hannover, Germany
  • Köln, Germany
  • München, Germany
• Poland
  • Bydgoszcz, Poland
  • Chorzow, Poland
  • Krakow, Poland
  • Lodz, Poland
  • Szczecin, Poland
  • Warszawa, Poland
  • Wroclaw, Poland
• Puerto Rico
  • San Juan, Puerto Rico
• Russian Federation
  • Ekaterinburg, Russian Federation
  • Krasnodar, Russian Federation
  • Orel, Russian Federation
  • Saint Petersburg, Russian Federation
  • Saratov, Russian Federation
  • Smolensk, Russian Federation
  • Tolyatti, Russian Federation
  • Voronezh, Russian Federation
• Spain
  • Alicante, Spain
  • Badalona, Spain
  • Barcelona, Spain
  • Cordoba, Spain
  • Elche, Spain
  • Madrid, Spain
  • Santiago de Compostela, Spain
  • Sevilla, Spain
  • Valencia, Spain
• United Kingdom
  • Brighton, United Kingdom
  • Bristol, United Kingdom
  • London, United Kingdom
• United States
  • Alabama
    • Birmingham, Alabama, United States
  • Arizona
    • Phoenix, Arizona, United States
  • California
    • Bakersfield, California, United States
    • Long Beach, California, United States
    • Los Angeles, California, United States
    • North Hollywood, California, United States
    • San Francisco, California, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Fort Pierce, Florida, United States
    • Miami, Florida, United States
    • Orlando, Florida, United States
    • West Palm Beach, Florida, United States
  • Georgia
    • Savannah, Georgia, United States
  • Massachusetts
    • Boston, Massachusetts, United States
    • Springfield, Massachusetts, United States
  • Michigan
    • Berkley, Michigan, United States
  • Minnesota
    • Minneapolis, Minnesota, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • New Jersey
    • Hillsborough, New Jersey, United States
    • Newark, New Jersey, United States
    • Somers Point, New Jersey, United States
  • New Mexico
    • Santa Fe, New Mexico, United States
  • New York
    • Manhasset, New York, United States
  • North Carolina
    • Chapel Hill, North Carolina, United States
    • Winston-Salem, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Texas
    • Fort Worth, Texas, United States
    • Houston, Texas, United States
  • Washington
    • Seattle, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject must be antiretroviral (ARV) treatment-naive (never treated with an ARV including post-exposure prophylaxis and pre-exposure prophylaxis); no prior use of any approved or experimental anti- human immunodeficiency virus (anti-HIV) drug for any length of time
• Screening plasma HIV-1 ribonucleic acid (RNA) level greater than or equal to >=1,000 copies per milliliter (copies/mL)
• Cluster of Differentiation 4+ (CD4+) cell count >50 cells/microliter (cells/mcL)
• Screening HIV-1 genotype report must show full sensitivity to DRV, TDF and FTC
• Screening eGFRcreatinine >=70 mL/min according to the Cockcroft-Gault formula for creatinine clearance

Exclusion Criteria:

• Subject has been diagnosed with a new acquired immunodeficiency syndrome (AIDS)-defining condition within the 30 days prior to screening
• Subject has proven or suspected acute hepatitis within 30 days prior to screening
• Subject is hepatitis C or hepatitis B positive
• Subject has a history of cirrhosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide; Subject will receive a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination [FDC]) once daily along with DRV/COBI FDC-matching and FTC/TDF FDC-matching placebo tablets once daily up to Week 48 analysis unblinding visit (i.e. after last subject has reached Week 48). After Week 48 analysis unblinding visit, subjects will receive a single tablet containing D/C/F/TAF FDC once daily up to Week 96.	Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC; A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF) 10 mg will be administered once daily.; Drug: FTC/TDF FDC Matching Placebo; Matching placebo of FTC/TDF FDC will be administered once daily.; Drug: DRV/COBI FDC Matching Placebo; Matching placebo of DRV/COBI FDC will be administered once daily.
Active Comparator: DRV/COBI fixed dose combination (FDC) and FTC/TDF FDC; Subject will receive DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48 analysis unblinding (i.e. after last subject has reached Week 48). After Week 48 analysis unblinding, subjects will receive a single tablet containing D/C/F/TAF FDC once daily up to Week 96.	Drug: DRV/COBI FDC; A tablet containing DRV 800 mg and COBI 150 mg will be administered once daily.; Drug: FTC/TDF FDC; A tablet containing FTC 200 mg and TDF 300 mg will be administered once daily.; Drug: D/C/F/TAF FDC - Matching Placebo; Matching placebo of D/C/F/TAF FDC will be administered once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies Per mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach	Percentage of participants with a HIV-1 RNA < 50 copies per mL were assessed using FDA snapshot approach 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. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA < 20/50/200 copies per mL at Week 48), 2) virologic failure (HIV RNA greater than or equal to [>=] 20/50/200 copies per mL at Week 48), 3) no viral load data in the Week 48 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response.	At Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach	Percentage of participants with HIV-1 RNA < 20/200 copies per mL using FDA snapshot approach were reported. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA < 20/50/200 copies per mL at Week 48 and 96), 2) virologic failure (HIV RNA >= 20/50/200 copies per mL at Week 48 and 96), 3) no viral load data in the Week 48 and 96 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response.	At Weeks 48 and 96
Percentage of Participants With HIV-1 RNA < 20, 50, and 200 Copies Per mL at Week 48 and 96 Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm	Percentage of participants with HIV-1 RNA less than (<) 20, 50, and 200 copies per mL at Weeks 48 and 96 based on TLOVR algorithm were assessed. TLOVR requires sustained HIV-1 RNA < 50 copies per mL; confirmed HIV-1 RNA >= 50 copies per mL is considered as non-response (rebound); participant is considered non-responder after permanent discontinuation.	At Week 48 and 96
Change From Baseline in log10 HIV-1 RNA Levels at Week 48	Change from baseline in log10 HIV-1 RNA levels were reported.	Baseline and Week 48
Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Week 48	The immunologic change was determined by changes in Cluster of CD4+ cell count. Change from baseline in CD4+ cell count at Week 48 were assessed.	Baseline and Week 48
Change From Baseline in Serum Creatinine at Week 48	Change from baseline in serum creatinine at Week 48 was reported.	Baseline and Week 48
Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Formula at Week 48	Change from baseline in eGFRcr was calculated using the CKD-EPI equation as per which Stage 1 (normal or high GFR [>=90 mL/min]); Stage 2 (Mild CKD [60 to 90 mL/min]); Stage 3 (Moderate CKD [30 to 59mL/min]); Stage 4 (Severe CKD [15 to 29 mL/min]); Stage 5 (End Stage CKD [<15 mL/min]). The eGFRcr was assessed by calculating serum creatinine (Scr) using the equation: eGFRcr milliliter per minute per 1.72 meter square (mL/min/1.73m^2) = 144*(Scr/0.7)^-0.329*0.993^age (Scr =< 0.7 mg/dL) and eGFRcr mL/min/1.73m^2 = 144*(Scr/0.7)^-1.209*0.993^age (Scr >0.7 mg/dL) for female participants and eGFRcr mL/min/1.73m^2 = 141*(Scr/0.9)^-0.411*0.993^age (Scr =<0.9 mg/dL) and eGFRcr mL/min/1.73m^2 = 141*(Scr/0.9)^-1.209*0.993^age (Scr >0.9 mg/dL) for male participants.	Baseline and Week 48
Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine by (Cockcroft-Gault Formula) at Week 48	Change from baseline in eGFRcr by cockcroft-gault formula at Week 48. The eGFRcr was assessed by calculated creatinine clearance (CrCl) using the Cockcroft-Gault formula, and was assessed using CrCl [mL/min] = (140 - A) * W / (72 * C) * R. Where A is age at sample date [years], W is body weight at specific visit (kilogram [kg]), C is the serum concentration of creatinine [mg/dL], R = 1 if the participant is male and = 0.85 if female.	Baseline and Week 48
Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula at Week 48	Change from baseline in eGFRcyst was calculated using the CKD-EPI equation as per which Stage 1 (normal or high GFR) >= 90 indicates normal kidney function; Stage 2 (Mild CKD): 60 to 89 mL/min indicates mildly reduced kidney function; Stage 3 (Moderate CKD): 30 to 59 mL/min indicates moderately reduced kidney function; Stage 4 (Severe CKD): 15 to 29 mL/min indicates severely reduced kidney function; Stage 5 (End Stage of CKD): <15 mL/min indicate very severe or end stage kidney failure. The eGFRcyst was assessed by calculated serum cystatin C (Scyst) using the equation: eGFRcyst mL/min/1.73m^2 = 133 * (Scyst/0,8)^-0.499 * 0.996^age [* 0.932 if female] (Scyst =<0.8 mg/L) and eGFRcr mL/min/1.73m^2 = 133 * (Scyst/0,8)^-1.328 * 0.996^age [* 0.932 if male] (Scyst >0.8 mg/L).	Baseline and Week 48
Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 48	AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. SAE is any adverse event (AE) that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.	Up to Weeks 48
Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Week 48	Change from baseline in UPCR at Week 48 was reported.	Baseline and Week 48
Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) at Week 48	Change from baseline in UACR at Week 48 was reported.	Baseline and Week 48
Change From Baseline in Urine Retinol Binding Protein To Creatinine Ratio (URBPCR) at Week 48	Change from baseline in URBPCR at Week 48 were reported.	Baseline and Week 48
Change From Baseline in Urine Beta-2 Microglobulin to Creatinine Ratio (UB2MGCR) at Week 48	Change from baseline in UB2MGCR at Week 48 were reported.	Baseline and Week 48
Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Week 48	Percent change from baseline in FEPO4 at Week 48 was reported.	Baseline and Week 48
Area Under the Plasma Concentration-Time Curve From Time of Administration to 24 Hours Post-dose (AUC0-24h) of Darunavir	AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours post-dose.	0 to 24 hours post dose
Predose (Trough) Plasma Concentration (C0h) of Darunavir	C0h is defined as the predose (trough) plasma concentration or concentration just prior to study drug administration.	30 minutes to 4 hours postdose at Weeks 2, 4, 12, 24 and 48 and at 2 timepoints with at least 2.5 hours in between sampling at Week 8 and 36 (first sample between 1 and 4 hours postdose)
Area Under the Plasma Concentration Time Curve Across the Dosing Interval (AUCtau) of Tenofovir Alafenamide	The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.	30 minutes to 4 hours postdose at Weeks 2, 4, 12, 24 and 48 and at 2 timepoints with at least 2.5 hours in between sampling at Week 8 and 36 (first sample between 1 and 4 hours postdose)
Plasma Concentrations 2 Hours After Dosing (C0-2h) of Tenofovir Alafenamide	C0-2h is defined as the plasma concentrations 2 hours after dosing.	0 to 2 hours post dose
Percent Change From Baseline in Hip and Spine Bone Mineral Density (BMD)	The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by dual energy x-ray absorptiometry (DEXA) scan. Positive values are "best values" and negative values are "worst values" of change. Percent change from baseline in hip and spine BMD was assessed.	Baseline, Weeks 24 and 48
Change From Baseline in BMD T-score of Hip and Spine	BMD status was assessed using BMD T-scores; normal bone status was defined by a BMD T-score >= -1, osteopenia by a T-score >= -2.5 to <-1.0, and osteoporosis by a T-score <-2.5.	Baseline, Weeks 24 and 48
Change From Baseline in Alkaline Phosphatase (ALP) Levels at Weeks 24 and 48	Change from baseline in ALP at Weeks 24 and 48 was reported.	Baseline, Weeks 24 and 48
Change From Baseline in Levels of Serum Procollagen 1 N-Terminal Propeptide (P1NP) at Weeks 24 and 48	Change from baseline in serum P1NP at Weeks 24 and 48 were reported.	Baseline, Weeks 24 and 48
Change From Baseline in Levels of Serum Collagen Type 1 Beta Carboxy Telopeptide (CTX) at Weeks 24 and 48	Change from baseline in serum CTX at Weeks 24 and 48 were reported.	Baseline, Weeks 24 and 48
Change From Baseline in Levels of Parathyroid Hormone (PTH) at Weeks 24 and 48	Change from baseline in PTH at Weeks 24 and 48 were reported.	Baseline, Weeks 24 and 48
Change From Baseline in Levels of 25-Hydroxyvitamin D (25-OH Vitamin D), at Week 24 and 48	Change from baseline in 25-OH Vitamin D levels at Week 24 and 48 were reported.	Baseline, Weeks 24 and 48
Percentage of Participants With HIV-1 RNA <50 Copies Per mL at Week 96 Defined by FDA Snapshot Approach	Percentage of participants with a HIV-1 RNA < 50 copies per mL were assessed using FDA snapshot approach 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. The snapshot approach classified participants into 3 outcome categories: 1) virologic success (HIV RNA < 20/50/200 copies per mL at Week 96), 2) virologic failure (HIV RNA greater than or equal to [>=] 20/50/200 copies per mL at Week 96), 3) no viral load data in the Week 96 visit window (discontinued due to adverse event/death/other reason). The missing HIV-1 RNA is considered as non-response.	At Week 96
Change From Reference in log10 HIV-1 RNA Levels at Week 96	Change from reference in log10 HIV-1 RNA levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for Test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in CD4+ Cell Count at Week 96	The immunologic change was determined by changes in cluster of differentiation (CD4+) cell count. Change from reference in CD4+ cell count at Week 96 was assessed. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Percentage of Participants With >95% Treatment Adherence Assessed by Drug Accountability	Treatment adherence assessed by drug accountability (based on pill count) from start of treatment/switch to last study drug intake by determination of the cumulative treatment adherence in participants who returned all dispensed bottles prior to or at the last visit in the study. Adherent participants were defined as having an adherence >95% as assessed by drug accountability.	Baseline to Switch and switch to EOE to Open-Label D/C/F/TAF (Up to 3 years)
Percentage of Participants With Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations Due to Adverse Events Through Week 96	AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. SAE is any adverse event (AE) that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.	Up to Week 96
Change From Reference in Serum Creatinine	Change from reference in serum creatinine was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in eGFRcr by CKD-EPI Formula	Change from reference in eGFRcr was calculated using the CKD-EPI equation as per Stage 1 (normal or high GFR) to Stage 5 (End Stage of CKD). The eGFRcr was assessed by calculating serum creatinine (Scr) using the CKD-EPI equation: eGFRcr milliliter per minute per 1.72 meter square (mL/min/1.73m^2) = 144 * (Scr/0.7)^-0.329 * 0.993^age (Scr =< 0.7 mg/dL) and eGFRcr mL/min/1.73m^2 = 144 * (Scr/0.7)^-1.209 * 0.993^age (Scr >0.7 mg/dL) for female participants and eGFRcr mL/min/1.73m^2 = 141 x (Scr/0.9)^-0.411 x 0.993^age (Scr =<0.9 mg/dL) and eGFRcr mL/min/1.73m^2 = 141 * (Scr/0.9)^-1.209 x 0.993^age (Scr >0.9 mg/dL) for male participants. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine by Cockcroft-Gault Formula	Change from reference in eGFRcr by cockcroft-gault formula was reported. The eGFRcr was assessed by calculated creatinine clearance (CrCl) using the Cockcroft-Gault formula, and was assessed using CrCl [mL/min] = (140 - A) * W / (72 * C) * R. Where A is age at sample date [years], W is body weight at specific visit (kilogram [kg]), C is the serum concentration of creatinine [mg/dL], R = 1 if the participant is male and = 0.85 if female. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (eGFRcyst) by CKD-EPI Formula	Change from reference in eGFRcyst was calculated using the CKD-EPI equation as per Stage 1 (normal or high GFR) to Stage 5 (End Stage of CKD): <15 mL/min indicate very severe or end stage kidney failure. The eGFRcyst was assessed by calculated serum cystatin C (Scyst) using the CKD-EPI equation: eGFRcyst mL/min/1.73m^2 = 133 * (Scyst/0,8)^-0.499 * 0.996^age [x 0.932 if female] (Scyst =<0.8 mg/L) and eGFRcr mL/min/1.73m^2 = 133 * (Scyst/0,8)^-1.328 * 0.996^age [* 0.932 if male] (Scyst >0.8 mg/L). Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in UPCR	Change from reference in UPCR was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in UACR	Change from reference in UACR at Week 96 was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in URBPCR	Change from reference in URBPCR at Week 96 were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in UB2MGCR	Change from reference in UB2MGCR was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Percent Change From Reference in Urine FEPO4	Percent change from reference in FEPO4 at Week 96 were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Percent Change From Reference in Hip and Spine BMD	The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by DEXA scan. Positive values are "best values" and negative values are "worst values" of change. Percent change from reference in hip and spine BMD was assessed. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in BMD T-score of Hip and Spine at Week 96	BMD status was assessed using BMD T-scores; normal bone status was defined by a BMD T-score >= -1, osteopenia by a T-score >= -2.5 to <-1.0, and osteoporosis by a T-score <-2.5. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in ALP Levels	Change from reference in ALP levels at Week 96 was reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in Levels of Serum P1NP	Change from reference in serum P1NP levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in Levels of Serum CTX	Change from reference in serum CTX levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in Levels of PTH	Change from reference in PTH levels were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Change From Reference in Levels of 25-OH Vitamin D	Change from reference in 25-OH Vitamin D were reported. Here, reference 1 is the comparative phase baseline value in Week 48 analysis for test group and reference 2 is the last value prior to the switch for Control group.	From Reference 1 to Week 96 for D/C/F/TAF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Percentage of Participants With HIV RNA <50, <20, and <200 Copies/mL Post-week 96 to End of Extension	Percentage of participants with HIV RNA <50, <20, and <200 copies/mL post Week 96 to end of extension were reported.	Week 96 to end of extension (up to 3 years)
Percentage of Participants With Protocol-defined Virologic Failure (PDVF)	Percentage of participants with PDVF were reported. Protocol-defined virologic failure was defined as having virologic non-response (HIV-1 RNA <1 log10 reduction from baseline and >=50 copies/mL at the Week 8 visit, confirmed at the next visit), virologic rebound (confirmed HIV-1 RNA >=50 copies/mL after confirmed consecutive HIV-1 RNA <50 copies/mL or confirmed >1 log10 increase in HIV-1 RNA from nadir), or viremic at final time point (final available on treatment HIV-1 RNA >=400 copies/mL).	From Baseline up to Week 96
Percentage of Participants With PDVF Post-week 96 to End of Extension	Percentage of participants with PDVF were reported. Protocol-defined virologic failure was defined as having virologic non-response (HIV-1 RNA <1 log10 reduction from baseline and >=50 copies/mL at the Week 8 visit, confirmed at the next visit), virologic rebound (confirmed HIV-1 RNA >=50 copies/mL after confirmed consecutive HIV-1 RNA <50 copies/mL or confirmed >1 log10 increase in HIV-1 RNA from nadir), or viremic at final time point (final available on treatment HIV-1 RNA >=400 copies/mL).	Week 96 to end of extension (up to 3 years)
Percentage of Participants With Non-PDVF by Kaplan-Meier Estimates	Percentage of participants with non-PDVF by Kaplan-Meier Estimates were reported. PDVF was defined as having virologic non-response (HIV-1 RNA <1 log10 reduction from baseline and >=50 copies/mL at the Week 8 visit, confirmed at the next visit), virologic rebound (confirmed HIV-1 RNA >=50 copies/mL after confirmed consecutive HIV-1 RNA <50 copies/mL or confirmed >1 log10 increase in HIV-1 RNA from nadir), or viremic at final time point (final available on treatment HIV-1 RNA >=400 copies/mL).	From Week 96 to end of extension (up to 2 years and 6 months)
Percentage of Participants With Time to Treatment Failure by Kaplan-Meier Estimates	Percentage of participants with time to treatment failure by Kaplan-Meier Estimates were reported. Treatment failure was defined as having either protocol-defined virologic failure or having discontinued for reasons other than alternate access to D/C/F/TAF (or other ARVs).	From Week 96 to end of extension (up to 3 years)
CD4+ Cell Count Post-Week From 96 to End of Extension	The immunologic change was determined by Cluster of CD4+ cell count. CD4+ cell count post-Week 96 to end of extension were assessed.	Week 96 to end of extension (up to 3 years)
Number of Participants With ARV Resistance	Number of participants with DRV, FTC, TDF/TAF resistance were reported.	Baseline to end of extension (up to 4 years)
Percentage of Participants With Grade 3 and 4 AEs, SAEs, and Premature Discontinuations Due to Adverse Events Post-Week 96 to End of Extension	AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events. SAE is any adverse event (AE) that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.	From Week 96 to end of extension (up to 3 years)

Collaborators and Investigators

• Sponsor: Janssen Sciences Ireland UC

Publications and helpful links

General Publications

• Ackaert O, McDougall D, Perez-Ruixo C, Perez-Ruixo JJ, Jezorwski J, Crauwels HM. 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). AAPS J. 2021 Jun 7;23(4):82. doi: 10.1208/s12248-021-00607-8.
• Lathouwers E, Wong EY, Brown K, Baugh B, Ghys A, Jezorwski J, Mohsine EG, Van Landuyt E, Opsomer M, De Meyer S; AMBER and EMERALD Study Groups. 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. AIDS Res Hum Retroviruses. 2020 Jan;36(1):48-57. doi: 10.1089/AID.2019.0111. Epub 2019 Oct 21.
• Orkin C, Eron JJ, Rockstroh J, Podzamczer D, Esser S, Vandekerckhove L, Van Landuyt E, Lathouwers E, Hufkens V, Jezorwski J, Opsomer M; AMBER study group. Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. AIDS. 2020 Apr 1;34(5):707-718. doi: 10.1097/QAD.0000000000002463.
• Rashbaum B, Spinner CD, McDonald C, Mussini C, Jezorwski J, Luo D, Van Landuyt E, Brown K, Wong EY. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive patients with HIV-1: subgroup analyses of the phase 3 AMBER study. HIV Res Clin Pract. 2019 Feb;20(1):24-33. doi: 10.1080/15284336.2019.1608714. Epub 2019 May 29.
• Eron JJ, Orkin C, Gallant J, Molina JM, Negredo E, Antinori A, Mills A, Reynes J, Van Landuyt E, Lathouwers E, Hufkens V, Jezorwski J, Vanveggel S, Opsomer M; AMBER study group. A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. AIDS. 2018 Jul 17;32(11):1431-1442. doi: 10.1097/QAD.0000000000001817.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2015
• Primary Completion (Actual): March 2, 2017
• Study Completion (Actual): September 30, 2020

Study Registration Dates

• First Submitted: April 27, 2015
• First Submitted That Met QC Criteria: April 27, 2015
• First Posted (Estimate): April 30, 2015

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 27, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Tenofovir Alafenamide; Darunavir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate; Immunodeficiency Virus Type 1, Human
• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Emtricitabine tenofovir alafenamide; Cobicistat; Darunavir; Cobicistat mixture with darunavir
• Other Study ID Numbers: CR107277; TMC114FD2HTX3001 (Other Identifier: Janssen Sciences Ireland UC); 2015-000754-38 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No