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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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02431247
First Posted: April 30, 2015
Last Update Posted: October 10, 2017
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.
Information provided by (Responsible Party):
Janssen Sciences Ireland UC
  Purpose
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.

Condition Intervention Phase
Immunodeficiency Virus Type 1, Human Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC Drug: DRV/COBI FDC Drug: FTC/TDF FDC Drug: D/C/F/TAF FDC - Matching Placebo Drug: FTC/TDF FDC Matching Placebo Drug: DRV/COBI FDC Matching Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Janssen Sciences Ireland UC:

Primary Outcome Measures:
  • Percentage of Participants With Human Immunodeficiency Virus (HIV) -1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies per Milliliter (copies/mL) defined by FDA Snapshot Approach [ Time Frame: Week 48 ]
    FDA Snapshot Approach is based on the last observed viral load data within the Week 48 window: virologic response is defined as HIV-1 RNA <50 copies/mL (observed case); missing HIV-1 RNA is considered as non-response.


Secondary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA Less Than (<) 50 Copies/mL by FDA Snapshot Approach [ Time Frame: Week 96 ]
    FDA Snapshot Approach is based on the last observed viral load data within the Week 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 HIV-1 RNA Less Than (<) 50 Copies/mL Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm [ Time Frame: Week 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.

  • Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Week 48 and 96 [ Time Frame: Baseline, Week 48 and 96 ]
    The immunologic change will be determined by changes in Cluster of Differentiation 4 (CD4+) cell count.

  • Percentage of Participants With Resistance to antiretrovirals (ARVs) and Type of Resistance in Participants with Virologic Failure [ Time Frame: Up to Week 48 and 96 ]
    Presence of emerging resistance-Associated Mutations by ARV-class in the HIV-viruses.

  • Change From Baseline in Serum Creatinine, eGlomerular Filteration Rate-Creatinine (eGFR Creatinine) and eGFR Cystatin C at Week 48 and 96 [ Time Frame: Baseline, Week 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 eGFRcystC (by CKD- EPI method) at Week 48 and 96 will be assessed.

  • Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuations due to AEs [ Time Frame: Up to Weeks 48 and 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.

  • Change From Baseline in Renal Biomarkers at Week 48 and 96 [ Time Frame: Baseline, Week 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, Week 24, 48, and 96 ]
    BMD measured by DXA (dual energy x-ray absorptiometry) at lumbar spine (L1-L4) and for total hip (femoral neck, trochanter and inter-trochanter areas).


Enrollment: 725
Actual Study Start Date: July 6, 2015
Estimated Study Completion Date: April 5, 2020
Primary Completion Date: March 2, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

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, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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): NCT02431247


  Show 81 Study Locations
Sponsors and Collaborators
Janssen Sciences Ireland UC
Investigators
Study Director: Janssen Sciences Ireland UC Clinical Trial Janssen Sciences Ireland UC
  More Information

Responsible Party: Janssen Sciences Ireland UC
ClinicalTrials.gov Identifier: NCT02431247     History of Changes
Other Study ID Numbers: CR107277
TMC114FD2HTX3001 ( Other Identifier: Janssen Sciences Ireland UC )
2015-000754-38 ( EudraCT Number )
First Submitted: April 27, 2015
First Posted: April 30, 2015
Last Update Posted: October 10, 2017
Last Verified: October 2017

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

Keywords provided by Janssen Sciences Ireland UC:
Immunodeficiency Virus Type 1, Human
Darunavir
Cobicistat
Tenofovir Alafenamide
Emtricitabine
Tenofovir Disoproxil Fumarate

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir
Emtricitabine
Darunavir
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Cobicistat
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
HIV Protease Inhibitors
Protease Inhibitors
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors