Overview

This trial is active, not recruiting.

Condition human immunodeficiency virus type 1
Treatments d/c/f/taf, boosted protease inhibitor (bpi), ftc/tdf
Phase phase 3
Sponsor Janssen R&D Ireland
Start date March 2015
End date September 2017
Trial size 1153 participants
Trial identifier NCT02269917, 2014-003052-31, CR105736, TMC114IFD3013

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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).
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)
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).
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.
ftc/tdf
Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF).

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
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
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
Change From Baseline in Cluster of Differentiation (CD) 4+ Cell Counts at Week 24, 48, and 96
time frame: Week 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
Percentage of Participants With Resistance to ARVs and Type of Resistance in Participants with Virologic Rebound
time frame: Baseline, Week 24, 48 and 96
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
Change from Baseline in Renal Biomarkers at Weeks 24, 48, and 96
time frame: Baseline and Week 24, 48, and 96
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

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Janssen R&D Ireland.