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
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|ClinicalTrials.gov Identifier: NCT02269917|
Recruitment Status : Active, not recruiting
First Posted : October 21, 2014
Last Update Posted : February 12, 2018
|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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1153 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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 29, 2019|
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).
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).
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02269917
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|Study Director:||Janssen R&D Ireland Clinical Trial||Janssen R&D Ireland|