Clinical Trials

MainTitle

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.
Sponsor
Janssen R&D Ireland


Information provided by (Responsible Party)
Janssen R&D Ireland
ClinicalTrials.gov Identifier
NCT02269917

First received: October 17, 2014
Last updated: October 1, 2019
Last Verified: September 2019
History of Changes
Purpose

Purpose

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 (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 48 [ Time Frame: Through Week 48 ]
    Virologic rebound was defined as: confirmed plasma human immunodeficiency virus - 1 (HIV-1) Ribonucleic Acid (RNA) level greater than or equal to (>=)50 copies per milliliter (copies/mL) up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA >=50 copies/mL at premature discontinuation (irrespective of reason). Percentage of participants with virologic rebound were reported.
Secondary Outcome Measures:
  • Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=20 Copies/mL) Cumulative Through 48 Weeks [ Time Frame: Through 48 Weeks ]
    Virologic rebound was defined as: confirmed plasma HIV-1 RNA >=20 copies/mL up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA >=20 copies/mL at premature discontinuation (irrespective of reason). Percentage of participants with virologic rebound were reported.
  • Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=200 Copies/mL) Cumulative Through 48 Weeks [ Time Frame: Through 48 Weeks ]
    Virologic rebound was defined as: confirmed plasma HIV-1 RNA >=200 copies/mL up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA >=200 copies/mL at premature discontinuation (irrespective of reason). Percentage of participants with virologic rebound were reported.
  • Time to Virologic Rebound [ Time Frame: Baseline up to Week 48 ]
    Time to virologic rebound was calculated from baseline until the first rebound time point (that is, time point before confirmation of rebound). Virologic rebound was defined as: confirmed plasma HIV-1 RNA >=50 copies/mL up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA >=50 copies/mL at premature discontinuation (irrespective of reason).
  • Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs) [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 3 (Severe) events were symptoms causing inability to perform usual social & functional activities. Grade 4 (Life-threatening) events were symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death.
  • Change From Baseline in Serum Creatinine Levels at Weeks 24 and 48 [ Time Frame: Baseline and Weeks 24 and 48 ]
    Change from baseline in serum creatinine levels at Weeks 24 and 48 was assessed.
  • Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Weeks 24 and 48 [ Time Frame: Baseline, Weeks 24 and 48 ]
    Change from baseline in eGFRcr (by Cockcroft-Gault formula) was assessed at Weeks 24 and 48. eGFRcr according to the Cockcroft Gault formula- Male: (140 - age in years)*(weight in kilogram [kg])/72*(serum creatinine in milligram per deciliter [mg/dL])=eGFRcr (milliliter per minute [mL/min]); Female: (140 - age in years)*(weight in kg)/72*(serum creatinine in mg/dL)*0.85=eGFRcr (mL/min).
  • 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 [ Time Frame: Baseline, Weeks 24 and 48 ]
    Change from baseline in eGFRcr (by CKD-EPI) was assessed at Weeks 24 and 48. eGFRcr per CKD-EPI formula - Female: 1) Serum creatinine (Scr) less than or equal to (<=)0.7 mg/dL: 144*(Scr/0.7)^-0.329*0.993age; 2) Scr greater than (>)0.7 mg/dL: 144*(Scr/0.7)^-1.209*0.993age. Male: 1) Scr <=0.9 mg/dL: 141*(Scr/0.9)^-0.411*0.993age; 2) Scr >0.9 mg/dL: 141*(Scr/0.9)^-1.209*0.993age.
  • 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 [ Time Frame: Baseline, Weeks 24 and 48 ]
    Change from baseline in eGFRcyst (by CKD-EPI) was assessed at Weeks 24 and 48. eGFRcyst according to the CKD-EPI formula - 1) Serum Cystatin C (Scyst) <=0.8 mg/L: 133*(Scyst/0.8)^-0.499*0.996age (*0.932 if female); 2) Scyst >0.8 mg/L: 133*(Scyst/0.8)^-1.328*0.996age (*0.932 if female).
  • Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48 [ Time Frame: Baseline, Weeks 24 and 48 ]
    Change from baseline in UACR and UPCR was assessed at Weeks 24 and 48. Lower levels of albumin or protein in the urine indicates better proximal tubular function.
  • 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 [ Time Frame: Baseline, Weeks 24 and 48 ]
    Change from baseline in URBPCR and UB2MGCR was assessed at Weeks 24 and 48. Retinol binding protein is a marker of proximal tubular function.
  • Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Weeks 24 and 48 [ Time Frame: Baseline, Weeks 24 and 48 ]
    Percent change from baseline in urine FEPO4 was assessed at Weeks 24 and 48.
  • 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 [ Time Frame: Week 48 ]
    Percentage of participants with virologic response based on HIV-1 RNA <20, <50, and <200 copies/mL threshold were analyzed at Week 48 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic response was defined as HIV-1 RNA <20/50/200 copies/mL (observed case).
  • 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 [ Time Frame: Week 48 ]
    Percentage of participants with virologic response based on HIV-1 RNA <20, <50, and <200 copies/mL threshold were analyzed at Week 48 using TLOVR algorithm approach. TLOVR was defined as sustained HIV-1 RNA <20/50/200 copies/mL.
  • Change From Baseline in Cluster of Differentiation 4 Plus (CD4+) Cell Count at Weeks 24 and 48 [ Time Frame: Baseline, Weeks 24 and 48 ]
    Change from baseline in CD4+ cell count was assessed at Weeks 24 and 48.
  • Percentage of Participants With Treatment Adherence of Greater Than (>)95 Percent (%) (Approach 1) Through Week 48 [ Time Frame: Through Week 48 ]
    Treatment adherence (defined as adherence of >95%) was assessed by the drug accountability cumulative through Week 48 (Approach 1).
  • Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 48 [ Time Frame: Through Week 48 ]
    Treatment adherence (defined as adherence of >95%) was assessed by the drug accountability cumulative treatment adherence up to time point where not more than one bottle was missing, or if available, through Week 48, whichever came sooner (Approach 2).
  • Number of Participants With Resistance to Study Drug [ Time Frame: Up to Week 48 ]
    HIV-1 genotypes were analyzed from samples of participants with confirmed virologic rebound (virologic rebound was defined as: confirmed HIV-1 RNA >=50 copies/mL up to, and including the upper bound of the Week 48 window) and with HIV-1 RNA value greater than or equal to (>=)400 copies/mL or who discontinued with last HIV-1 RNA >=400 copies/mL. Number of participants who developed resistance to any of the study drug was determined.
  • Predose (Trough) Plasma Concentration (C0h) of Darunavir [ Time Frame: Predose at Weeks 2, 4, 8, 12, 24, 36, and 48 ]
    Predose (trough) plasma concentration (C0h) of darunavir was determined. Pharmacokinetic (PK) data was only analyzed for participants in the D/C/F/TAF group as per planned analysis.
  • 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 [ Time Frame: Baseline, Weeks 24 and 48 ]
    Percent change from baseline in bone biomarkers: P1NP and CTX was assessed at Weeks 24 and 48.
  • Percent Change From Baseline in Parathyroid Hormone (PTH) at Weeks 24 and 48 [ Time Frame: Baseline, Weeks 24 and 48 ]
    Percent change from baseline in bone biomarker: PTH was assessed at Weeks 24 and 48.
  • Percent Change From Baseline in 25-hydroxy Vitamin D at Weeks 24 and 48 [ Time Frame: Baseline, Weeks 24 and 48 ]
    Percent change from baseline in bone biomarker: 25-hydroxy vitamin D was assessed at Weeks 24 and 48.
  • Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48 [ Time Frame: Baseline, Weeks 24 and 48 ]
    Percent change from baseline in spine and hip BMD was assessed at Weeks 24 and 48.
  • Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48 [ Time Frame: Baseline, Weeks 24 and 48 ]
    Change from baseline in spine, hip, and femoral neck BMD T-Score was assessed at Week 24 and 48. T-score values >= -1.0 were considered normal, T-score values < -1.0 to -2.5 indicate osteopenia and T-score values < -2.5 indicate osteoporosis.

Enrollment: 1149
Study Start Date: March 30, 2015
Estimated Study Completion Date: June 1, 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.

Drug: FTC/TDF

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.

Eligibility

Eligibility

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

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 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 ClinicalTrials.gov identifier: NCT02269917

Locations

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
Belgium
Antwerpen, Belgium
Brussels, Belgium
Bruxelles, Belgium
Gent, Belgium
Leuven, Belgium
Liège, Belgium
Canada
Edmonton, Alberta, Canada
Vancouver, British Columbia, Canada
Toronto, Ontario, Canada
Montreal, Quebec, Canada
France
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
Poland
Bydgoszcz, Poland
Chorzow, Poland
Lodz, Poland
Warszawa, Poland
Wroclaw, Poland
Puerto Rico
San Juan, Puerto Rico
Spain
Alicante, Spain
Badalona, Spain
Barcelona, Spain
Cordoba, Spain
Elche, Spain
Madrid, Spain
San Sebastian, Spain
Sevilla, Spain
Valencia, Spain
Sweden
Göteborg, Sweden
Malmö, Sweden
Stockholm, Sweden
Switzerland
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

Investigators

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

More Information


Responsible Party: Janssen R&D Ireland  
ClinicalTrials.gov Identifier: NCT02269917   History of Changes  
Other Study ID Numbers: CR105736  
  TMC114IFD3013  
  2014-003052-31  
Study First Received: October 17, 2014  
Last Updated: October 1, 2019  

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

Keywords provided by Janssen R&D Ireland:

Human Immunodeficiency Virus Type 1
Emerald
Darunavir
Cobicistat
Emtricitabine
Tenofovir Alafenamide

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Tenofovir
Emtricitabine
Darunavir
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Cobicistat
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this data on October 15, 2019
This information is provided by ClinicalTrials.gov.