ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02269917
Recruitment Status : Active, not recruiting
First Posted : October 21, 2014
Results First Posted : November 9, 2018
Last Update Posted : November 9, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen R&D Ireland

Brief 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.

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Type 1 Drug: D/C/F/TAF Drug: Boosted Protease Inhibitor (bPI) Drug: FTC/TDF Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1149 participants
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
Actual Study Start Date : March 30, 2015
Actual Primary Completion Date : February 17, 2017
Estimated Study Completion Date : March 31, 2020


Arm Intervention/treatment
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).




Primary Outcome Measures :
  1. 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 :
  1. 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.

  2. 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.

  3. 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).

  4. 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.

  5. 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.

  6. 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).

  7. 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.

  8. 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).

  9. 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.

  10. 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.

  11. 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.

  12. 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).

  13. 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.

  14. 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.

  15. 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).

  16. 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).

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02269917


  Show 82 Study Locations
Sponsors and Collaborators
Janssen R&D Ireland
Investigators
Study Director: Janssen R&D Ireland Clinical Trial Janssen R&D Ireland
  Study Documents (Full-Text)

Documents provided by Janssen R&D Ireland:
Statistical Analysis Plan  [PDF] April 5, 2017
Study Protocol  [PDF] May 29, 2015


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen R&D Ireland
ClinicalTrials.gov Identifier: NCT02269917     History of Changes
Other Study ID Numbers: CR105736
TMC114IFD3013 ( Other Identifier: Janssen R&D Ireland )
2014-003052-31 ( EudraCT Number )
First Posted: October 21, 2014    Key Record Dates
Results First Posted: November 9, 2018
Last Update Posted: November 9, 2018
Last Verified: November 2018

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:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Tenofovir
Emtricitabine
Darunavir
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Cobicistat
HIV Protease Inhibitors
Protease Inhibitors
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors