Clinical Trials


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

This study is ongoing, but not recruiting participants.
Janssen R&D Ireland

Information provided by (Responsible Party)
Janssen R&D Ireland Identifier

First received: October 17, 2014
Last updated: July 24, 2018
Last Verified: July 2018
History of Changes


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.

Condition Intervention Phase
Human Immunodeficiency Virus Type 1

Drug : D/C/F/TAF
Drug : Boosted Protease Inhibitor (bPI)
Drug : FTC/TDF
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Active-controlled, Open-label Study to Evaluate the Efficacy, Safety and Tolerability of Switching to a Darunavir/ Cobicistat/ Emtricitabine/ Tenofovir Alafenamide (D/C/F/TAF) Once-daily Single-tablet Regimen Versus Continuing the Current Regimen Consisting of a Boosted Protease Inhibitor (bPI) Combined With Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) in Virologically-suppressed, Human Immunodeficiency Virus Type 1 (HIV-1) Infected Subjects

Further study details as provided by Janssen R&D Ireland:

Primary Outcome Measures

  • Percentage of Participants With Virologic Rebound, (Confirmed), Plasma Human Immunodeficiency Virus - 1 (HIV-1) Ribonucleic Acid (RNA) Level >=50 Copies/mL through Week 48 [ Time Frame: Up to Week 48 ]
    Virologic rebound is defined as 1) participants who show confirmed HIV-1 RNA >= 50 copies/mL through Week 48 window or 2) participants who discontinued prematurely (irrespective of reason) for which the last available (single) HIV-1 RNA ≥ 50 copies/mL.
Secondary Outcome Measures:
  • Change From Baseline in Cluster of Differentiation (CD) 4+ Cell Counts at Week 24, 48, and 96 [ Time Frame: Week 24, 48, and 96 ]
    Participant's immunological status will be assessed by CD4+ cell count at Weeks 24, 48, and 96.
  • Percentage of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) of Grade 3 and 4, and Premature Discontinuations due to AEs [ Time Frame: Baseline up to Week 24, 48, and 96 ]
    An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grade 3 (Severe) events are symptoms causing inability to perform usual social & functional activities. Grade 4 (Life-threatening) events are Symptoms causing inability to perform basic self-care functions or Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death.
  • Percentage of Participants With Resistance to ARVs and Type of Resistance in Participants with Virologic Rebound [ Time Frame: Baseline, Week 24, 48 and 96 ]
    Presence of emerging Resistance-Associated Mutations by ARV-class in the HIV-virusses.
  • Change From Baseline in Serum Creatinine, Estimated Glomerular Filtration Rate for Creatinine Clearance (eGFRcr), and eGFR for Cystatin-C Clearance (eGFRcyst) at Week 24, 48 and 96 [ Time Frame: Up to Weeks 24, 48, and 96 ]
    The change from baseline in serum creatinine, eGFRcr (by Cockcroft-Gault and by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] methods) and eGFRcyst (by CKD-EPI method) at Week 24, 48 and 96 will be assessed.
  • Change from Baseline in Renal Biomarkers at Weeks 24, 48, and 96 [ Time Frame: Baseline and Week 24, 48, and 96 ]
    Renal biomarkers are retinol binding protein [RBP] and beta-2-microglobulin
  • Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24, 48, and 96 [ Time Frame: Baseline and Weeks 24, 48, and 96 ]
    BMD measured by DXA (dual energy xray absorptiometry) at lumbar spine, (L1-L4) and for total hip (femoral neck, trochanter and inter-trochanter areas). The data will be analyzed for participants participating in bone substudy.
  • Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL at Week 24, 48 and 96 per FDA Snapshot Approach [ Time Frame: Week 24, 48 and 96 ]
    FDA Snapshot approach analysis is based on the last observed viral load data within the Week 24, 48 and 96 window: virologic response is defined as HIV-1 RNA <50 copies/mL (observed case); missing HIV-1 RNA is considered as non-response.
  • Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL at Weeks 24, 48, and 96 per TLOVR algorithm [ Time Frame: Week 24, 48, and 96 ]
    Time to loss of virologic response algorithm (TLOVR) requires sustained HIV-1 RNA < 50 copies/mL; confirmed HIV-1 RNA more than or equal to (>=) 50 copies/mL is considered as non-response (rebound); participant is considered non-responder after permanent discontinuation.

Enrollment: 1153
Study Start Date: March 30, 2015
Estimated Study Completion Date: March 31, 2020
Estimated Primary Completion Date: February 17, 2017 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Experimental Treatment Regimen
Participants will receive a single fixed dose combination (FDC) tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF tablet), orally once daily, up to Week 48. After Week 48, all participants will continue to receive the D/C/F/TAF tablet in a 48 week extension phase (up to Week 96).
Drug: D/C/F/TAF

Once-daily single-tablet regimen containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg.

Active Comparator: Current Treatment Regimen
Participants will receive a boosted protease inhibitor (bPI) (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) up to Week 52. After Week 52, all participants will receive the D/C/F/TAF tablet in a 44 week extension phase (up to Week 96).
Drug: Boosted Protease Inhibitor (bPI)

Boosted protease inhibitor (limited to darunavir [DRV] or atazanavir with low-dose ritonavir [rtv] or cobicistat [COBI], or lopinavir with rtv) as per current treatment regimen.


Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF).

Detailed Description:

This is a randomized (study medication assigned to participants by chance), active-controlled (study in which the experimental treatment or procedure is compared to a standard treatment or procedure), open-label (participants and researchers are aware about the treatment, participants are receiving), multicenter (when more than 1 hospital or medical school team work on a medical research study), study in virologically-suppressed, HIV-1 infected adult participants. The study will include a Screening Period of approximately 30 days (up to maximum 6 weeks), a controlled Treatment Period of 48 weeks, an Extension Phase of 48 weeks. All eligible participants will be randomly assigned to receive either current treatment regimen - a bPI (limited to DRV with low-dose ritonavir [rtv] or COBI, atazanavir [ATV] with rtv or COBI, or lopinavir [LPV] with rtv) combined with FTC/TDF, or experimental treatment regimen - D/C/F/TAF once-daily single-tablet for 48 weeks. After completion of week 48, participants assigned to the experimental treatment will continue with D/C/F/TAF in the extension phase up to week 96 . Participants who continued their current regimen will receive the experimental treatment (if all criteria are fulfilled) at week 52 up to week 96. As from Week 96, all participants will be given the option to continue D/C/F/TAF treatment, if they wish and if they continue to benefit from it until D/C/F/TAF becomes commercially available and is reimbursed, or can be accessed through another source in the country where he/she is living,or until the sponsor terminates clinical development. A bone investigation substudy will be performed at selected study sites, to assess bone biomarkers and energy x-ray absorptiometry (DXA) scans, in approximately 300 participants (200 in the D/C/F/TAF treatment arm versus 100 in the control arm) who provide informed consent for the substudy.



Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  


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 per milliliter (copies/mL) or HIV-1 RNA undetectable by a local HIV-1 RNA test between 12 and 2 months prior to the Screening visit and have HIV-1 RNA <50 copies/mL at the Screening visit
  • A single virologic elevation of greater than or equal to (>=) 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

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02269917


United States, Arizona
Phoenix, Arizona, United States
United States, California
Bakersfield, California, United States
Beverly Hills, California, United States
Long Beach, California, United States
Los Angeles, California, United States
San Diego, California, United States
San Francisco, California, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Florida
Fort Lauderdale, Florida, United States
Fort Pierce, Florida, United States
Orlando, Florida, United States
West Palm Beach, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
Savannah, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
United States, Massachusetts
Boston, Massachusetts, United States
Springfield, Massachusetts, United States
United States, Michigan
Berkley, Michigan, United States
Detroit, Michigan, United States
United States, Minnesota
Minneapolis, Minnesota, United States
United States, Missouri
Kansas City, Missouri, United States
Saint Louis, Missouri, United States
United States, New Jersey
Hillsborough, New Jersey, United States
Newark, New Jersey, United States
Somers Point, New Jersey, United States
United States, New Mexico
Santa Fe, New Mexico, United States
United States, New York
New York, New York, United States
United States, North Carolina
Chapel Hill, North Carolina, United States
Winston-Salem, North Carolina, United States
United States, Ohio
Cincinnati, Ohio, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Rhode Island
Providence, Rhode Island, United States
United States, Texas
Austin, Texas, United States
Dallas, Texas, United States
Fort Worth, Texas, United States
Houston, Texas, United States
Longview, Texas, United States
United States, Washington
Seattle, Washington, United States
Antwerpen, Belgium
Brussels, Belgium
Bruxelles, Belgium
Gent, Belgium
Leuven, Belgium
Liège, Belgium
Edmonton, Alberta, Canada
Vancouver, British Columbia, Canada
Toronto, Ontario, Canada
Montreal, Quebec, Canada
Le Kremlin Bicetre, France
Lyon, France
Marseille, France
Montpellier, France
Nantes, France
Paris Cedex 10, France
Paris Cedex 12, France
Paris, France
Strasbourg Cedex, France
Tourcoing, France
Bydgoszcz, Poland
Chorzow, Poland
Lodz, Poland
Warszawa, Poland
Wroclaw, Poland
Puerto Rico
San Juan, Puerto Rico
Alicante, Spain
Badalona, Spain
Barcelona, Spain
Cordoba, Spain
Elche, Spain
Madrid, Spain
San Sebastian, Spain
Sevilla, Spain
Valencia, Spain
Göteborg, Sweden
Malmö, Sweden
Stockholm, Sweden
Basel, Switzerland
Bern, Switzerland
Zurich N/A, Switzerland
United Kingdom
Brighton, United Kingdom
London, United Kingdom
Manchester, United Kingdom

Sponsors and Collaborators

Janssen R&D Ireland


Study Director: Janssen R&D Ireland Clinical Trial Janssen R&D Ireland
More Information

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Additional Information:

To learn how to participate in this trial please click here.

Responsible Party: Janssen R&D Ireland Identifier: NCT02269917   History of Changes  
Other Study ID Numbers: CR105736  
Study First Received: October 17, 2014  
Last Updated: July 24, 2018  

Studies a U.S. FDA-regulated Device Product: No  

Keywords provided by Janssen R&D Ireland:

Human Immunodeficiency Virus Type 1
Tenofovir Alafenamide

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
HIV Protease Inhibitors
Protease Inhibitors processed this data on August 14, 2018
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