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
3 other identifiers
interventional
725
10 countries
80
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2015
Longer than P75 for phase_3
80 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 27, 2015
CompletedFirst Posted
Study publicly available on registry
April 30, 2015
CompletedStudy Start
First participant enrolled
July 6, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 2, 2017
CompletedResults Posted
Study results publicly available
September 14, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2020
CompletedSeptember 28, 2022
September 1, 2022
1.7 years
April 27, 2015
August 15, 2018
September 27, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (54)
Percentage of Participants With HIV-1 RNA <20 and 200 Copies Per mL at Weeks 48 and 96 Defined by FDA Snapshot Approach
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
At Week 48 and 96
Change From Baseline in log10 HIV-1 RNA Levels at Week 48
Baseline and Week 48
Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Week 48
Baseline and Week 48
Change From Baseline in Serum Creatinine at Week 48
Baseline and Week 48
- +49 more secondary outcomes
Study Arms (2)
Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide
EXPERIMENTALSubject 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.
DRV/COBI fixed dose combination (FDC) and FTC/TDF FDC
ACTIVE COMPARATORSubject 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.
Interventions
A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF) 10 mg will be administered once daily.
A tablet containing DRV 800 mg and COBI 150 mg will be administered once daily.
A tablet containing FTC 200 mg and TDF 300 mg will be administered once daily.
Matching placebo of D/C/F/TAF FDC will be administered once daily.
Matching placebo of FTC/TDF FDC will be administered once daily.
Matching placebo of DRV/COBI FDC will be administered once daily.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (80)
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Birmingham, Alabama, United States
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Phoenix, Arizona, United States
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Bakersfield, California, United States
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Long Beach, California, United States
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Los Angeles, California, United States
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North Hollywood, California, United States
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San Francisco, California, United States
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Washington D.C., District of Columbia, United States
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Ft. Pierce, Florida, United States
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Miami, Florida, United States
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Orlando, Florida, United States
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West Palm Beach, Florida, United States
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Savannah, Georgia, United States
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Boston, Massachusetts, United States
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Springfield, Massachusetts, United States
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Berkley, Michigan, United States
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Minneapolis, Minnesota, United States
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St Louis, Missouri, United States
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Hillsborough, New Jersey, United States
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Newark, New Jersey, United States
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Somers Point, New Jersey, United States
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Santa Fe, New Mexico, United States
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Manhasset, New York, United States
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Chapel Hill, North Carolina, United States
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Winston-Salem, North Carolina, United States
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Cincinnati, Ohio, United States
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Fort Worth, Texas, United States
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Houston, Texas, United States
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Seattle, Washington, United States
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Antwerp, Belgium
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Brussels, Belgium
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Ghent, Belgium
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Clamart, France
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Le Kremlin-Bicêtre, France
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Lyon, France
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Marseille, France
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Montpellier, France
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Nantes, France
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Paris, France
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Strasbourg, France
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Tourcoing, France
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Berlin, Germany
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Bonn, Germany
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Cologne, Germany
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Essen, Germany
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Frankfurt, Germany
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Freiburg im Breisgau, Germany
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Hamburg, Germany
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Hanover, Germany
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München, Germany
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Bydgoszcz, Poland
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Chorzów, Poland
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Krakow, Poland
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Lodz, Poland
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Szczecin, Poland
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Warsaw, Poland
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Wroclaw, Poland
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San Juan, Puerto Rico
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Krasnodar, Russia
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Oryol, Russia
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Saint Petersburg, Russia
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Saratov, Russia
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Smolensk, Russia
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Tolyatti, Russia
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Voronezh, Russia
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Yekaterinburg, Russia
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Alicante, Spain
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Badalona, Spain
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Barcelona, Spain
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Córdoba, Spain
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Elche, Spain
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Madrid, Spain
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Santiago de Compostela, Spain
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Seville, Spain
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Valencia, Spain
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Brighton, United Kingdom
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Bristol, United Kingdom
Unknown Facility
London, United Kingdom
Related Publications (5)
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.
PMID: 34100149DERIVEDOrkin 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.
PMID: 31833849DERIVEDLathouwers 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.
PMID: 31516033DERIVEDRashbaum 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.
PMID: 31303147DERIVEDEron 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.
PMID: 29683855DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Registry Group
- Organization
- Janssen Sciences Ireland UC
Study Officials
- STUDY DIRECTOR
Janssen Sciences Ireland UC Clinical Trial
Janssen Sciences Ireland UC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 27, 2015
First Posted
April 30, 2015
Study Start
July 6, 2015
Primary Completion
March 2, 2017
Study Completion
September 30, 2020
Last Updated
September 28, 2022
Results First Posted
September 14, 2018
Record last verified: 2022-09