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Trial record 1 of 1 for:    TMC114IFD3013
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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:
Information provided by (Responsible Party):
Janssen R&D Ireland
ClinicalTrials.gov Identifier:
NCT02269917
First received: October 17, 2014
Last updated: July 18, 2017
Last verified: July 2017
  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: No masking
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

Resource links provided by NLM:


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: 1154
Actual Study Start Date: March 30, 2015
Estimated Study Completion Date: October 11, 2019
Estimated Primary Completion Date: September 8, 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

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

  Show 82 Study Locations
Sponsors and Collaborators
Janssen R&D Ireland
Investigators
Study Director: Janssen R&D Ireland Clinical Trial Janssen R&D Ireland
  More Information

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 )
Study First Received: October 17, 2014
Last Updated: July 18, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
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

ClinicalTrials.gov processed this record on July 21, 2017