Back to resultsStudy 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
Primary Purpose
Human Immunodeficiency Virus Type 1
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
D/C/F/TAF
Boosted Protease Inhibitor (bPI)
FTC/TDF
Sponsored by
About this trial
This is an interventional treatment trial for Human Immunodeficiency Virus Type 1 focused on measuring Human Immunodeficiency Virus Type 1, Emerald, Darunavir, Cobicistat, Emtricitabine, Tenofovir Alafenamide
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Experimental Treatment Regimen
Current Treatment Regimen
Arm Description
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).
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).
Outcomes
Primary Outcome Measures
Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative 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
Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=20 Copies/mL) Cumulative 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.
Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=200 Copies/mL) Cumulative 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.
Percentage of Participants With Non-Virologic Rebound at Week 48 by Kaplan-Meier Estimates
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). Here Kaplan-Meier estimates percentage of participants with non-virologic rebound at week 48.
Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through 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.
Change From Baseline in Serum Creatinine Levels at Weeks 24 and 48
Change from baseline in serum creatinine levels at Weeks 24 and 48 was assessed.
Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at 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).
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
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.
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
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).
Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at 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.
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
Change from baseline in URBPCR and UB2MGCR was assessed at Weeks 24 and 48. Retinol binding protein is a marker of proximal tubular function.
Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Weeks 24 and 48
Percent change from baseline in urine FEPO4 was assessed at Weeks 24 and 48.
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
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).
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
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.
Change From Baseline in Cluster of Differentiation 4 Plus (CD4+) Cell Count at Weeks 24 and 48
Change from baseline in CD4+ cell count was assessed at Weeks 24 and 48.
Percentage of Participants With Treatment Adherence of Greater Than (>)95 Percent (%) (Approach 1) Through Week 48
Treatment adherence (defined as adherence of >95%) was assessed by the drug accountability cumulative through Week 48 (Approach 1).
Percentage of Participants With Treatment Adherence of >95% (Approach 2) 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).
Number of Participants With Resistance to Study Drug
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 >=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.
Predose (Trough) Plasma Concentration (C0h) of Darunavir
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.
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
Percent change from baseline in bone biomarkers: P1NP and CTX was assessed at Weeks 24 and 48.
Percent Change From Baseline in Parathyroid Hormone (PTH) at Weeks 24 and 48
Percent change from baseline in bone biomarker: PTH was assessed at Weeks 24 and 48.
Percent Change From Baseline in 25-hydroxy Vitamin D at Weeks 24 and 48
Percent change from baseline in bone biomarker: 25-hydroxy vitamin D was assessed at Weeks 24 and 48.
Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48
Percent change from baseline in spine and hip BMD was assessed at Weeks 24 and 48.
Change From Baseline in Bone Mineral Density (BMD) T-Score at 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.
Percentage of Participants With Virologic Rebound (HIV-1 RNA >=20 Copies/mL) Cumulative Through Week 96
Virologic rebound was defined as: confirmed plasma HIV-1 RNA level >=20 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA >=20 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA >=20 copies/mL at the study cutoff of Week 96 (that is, any last viral load [re]test having occurred no later than 6 weeks after Week 96). Percentage of participants with virologic rebound were reported.
Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 96
Virologic rebound was defined as: confirmed plasma HIV-1 RNA level >=50 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA >=50 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA >=50copies/mL at the study cutoff of Week 96 (that is, any last viral load [re]test having occurred no later than 6 weeks after Week 96). Percentage of participants with virologic rebound were reported.
Percentage of Participants With Virologic Rebound (HIV-1 RNA >=200 Copies/mL) Cumulative Through Week 96
Virologic rebound was defined as: confirmed plasma HIV-1 RNA level >=200 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA >=200 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA >=200 copies/mL at the study cutoff of Week 96 (that is, any last viral load [re]test having occurred no later than 6 weeks after Week 96). Percentage of participants with virologic rebound were reported.
Percentage of Participants With Non-Virologic Rebound at Week 96 by Kaplan-Meier Estimates
Here Kaplan-Meier estimates percentage of participants with non-virologic rebound at Week 96.
Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach
Percentage of participants with virologic response based on HIV-1 RNA <20, <50, and <200 copies/mL threshold were analyzed at Week 96 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic response was defined as having last available HIV-1 RNA <20/50/200 copies/mL (observed case).
Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the TLOVR Algorithm
Percentage of participants with virologic response based on HIV-1 RNA <20, <50, and <200 copies/mL threshold were analyzed at Week 96 using TLOVR algorithm approach. TLOVR was defined as sustained HIV-1 RNA <20/50/200 copies/mL.
Percentage of Participants With Virologic Failure Based on HIV-1 RNA >=20, >=50, and >=200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach
Percentage of participants with virologic failure based on HIV-1 RNA >=20, >=50, and >=200 copies/mL threshold were analyzed at Week 96 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic failure was defined by the FDA snapshot approach as having last available HIV-1 RNA >=20/50/200 copies/mL at Week 96; virologic failure - leading to discontinuation; virologic failure - discontinued due to other reason and last available HIV-1 RNA >=20/50/200 copies/mL.
Change From Reference in CD4+ Cell Count at Week 96
Change from reference in CD4+ cell count was assessed at Week 96. The change from reference in CD4+ count at a given time point is defined as: CD4+ at a given time point minus reference CD4+. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Number of Participants With Resistance to Study Drug Through Week 96
HIV-1 genotypes were analyzed from samples of participants with confirmed virologic rebound in case they had HIV-1 RNA values >=400 copies/mL at failure or at later time points, including participants who discontinued with last HIV-1 RNA >=400 copies/mL. Virologic rebound was defined as: confirmed plasma HIV-1 RNA level >=20 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA >=20 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA >=20 copies/mL at the study cutoff of Week 96 (that is, any last viral load [re]test having occurred no later than 6 weeks after Week 96). Number of participants who developed resistance to any of the study drug (DRV, FTC, and TFV/TAF) were reported.
Percentage of Participants With Treatment Adherence of >95 (Approach 1) Through Week 96
Treatment adherence (defined as adherence of >95%) was assessed by the drug accountability cumulative through Week 96 (Approach 1).
Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 96
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 96, whichever came sooner (Approach 2).
Percentage of Participants Experiencing Grade 3 and Grade 4 AEs, SAEs, and Premature Discontinuation Due to AEs Through Week 96
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. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Change From Reference in Serum Creatinine Levels at Week 96
Change from reference in serum creatinine levels at Week 96 was assessed. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Week 96
Change from reference in eGFRcr (by Cockcroft-Gault formula) was assessed at Week 96. 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). For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (by CKD-EPI) at Week 96
Change from reference in eGFRcr (by CKD-EPI) was assessed at Week 96. 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*0.993^age; 2) Scr greater than (>)0.7 mg/dL: 144*(Scr/0.7)^-1.209*0.993^age. Male: 1) Scr <=0.9 mg/dL: 141*(Scr/0.9)^-0.411*0.993^age; 2) Scr >0.9 mg/dL: 141*(Scr/0.9)^-1.209*0.993^age. . For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (by CKD-EPI) at Week 96
Change from reference in eGFRcyst (by CKD-EPI) was assessed at Week 96. eGFRcyst according to the CKD-EPI formula - 1) Serum Cystatin C (Scyst) <=0.8 mg/L: 133*(Scyst/0.8)^-0.499*0.996^age (*0.932 if female); 2) Scyst >0.8 mg/L: 133*(Scyst/0.8)^-1.328*0.996^age (*0.932 if female). For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Change From Reference in UACR at Week 96
Change from reference in UACR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Change From Reference in URBPCR at Week 96
Change from reference in URBPCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Change From Reference in UPCR at Week 96
Change from reference in UPCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Change From Reference in UB2MGCR at Week 96
Change from reference in UB2MGCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Percent Change From Reference in FEPO4 at Week 96
Percent change from reference in FEPO4 at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Percent Change From Reference in Levels of Serum P1NP at Week 96
Percent change from reference in serum P1NP levels at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Percent Change From Reference in Levels of Serum CTX at Week 96
Percent change from reference in serum CTX at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Percent Change From Reference in Levels of PTH at Week 96
Percent change from reference in PTH at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Percent Change From Reference in Levels of 25-OH Vitamin D at Week 96
Percent change from reference in 25-OH Vitamin D at Week 96 were reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Percent Change From Reference in Hip and Spine BMD at Week 96
The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by DXA scan. Positive values are "best values" and negative values are "worst values" of change. Percent change from reference in hip and spine BMD was assessed. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Change From Reference in BMD T-score of Hip and Spine at Week 96
BMD status was assessed using BMD T-scores; normal bone status was defined by a BMD T-score >= -1, osteopenia by a T-score >= -2.5 to <-1.0, and osteoporosis by a T-score <-2.5. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates
Virologic rebound is defined as participants who show confirmed HIV-1 RNA >=50 copies/mL, or for which the last available (single) HIV-1 RNA value on treatment was >=50 copies/mL. Here, Kaplan-Meier estimates (%) of non-virologic rebound at every 6 months interval are presented.
Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates
Percentage of participants with non-treatment failure by Kaplan-Meier Estimates were reported. Treatment failure was defined as having either protocol-defined virologic rebound or having discontinued for reasons other than alternate access to D/C/F/TAF (or other antiretroviral [ARV]).
Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension
Percentage of participants with HIV RNA <50, <20, <200 copies/mL post Week 96 to end of extension were reported.
CD4+ Cell Count Post-Week 96 to End of Extension
The immunologic change was determined by Cluster of CD4+ cell count. CD4+ cell count post-Week 96 to end of extension were assessed.
Percentage of Participants With Treatment Adherence of >95% From Week 96 to End of Extension
Treatment adherence (defined as adherence of >95%) was assessed by the drug accountability and was calculated cumulative from start of treatment/switch to last study drug intake by determination of the cumulative treatment adherence in participants who returned all dispensed bottles prior to or at the last visit in the study from Week 96 to end of extension.
Percentage of Participants Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Post-Week 96 to End of Extension
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. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Full Information
NCT ID
NCT02269917
First Posted
October 17, 2014
Last Updated
November 25, 2021
Sponsor
Janssen R&D Ireland
1. Study Identification
Unique Protocol Identification Number
NCT02269917
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
March 2015 (Actual)
Primary Completion Date
February 2017 (Actual)
Study Completion Date
October 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen R&D Ireland
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus Type 1
Keywords
Human Immunodeficiency Virus Type 1, Emerald, Darunavir, Cobicistat, Emtricitabine, Tenofovir Alafenamide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1149 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Experimental Treatment Regimen
Arm Type
Experimental
Arm Description
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).
Arm Title
Current Treatment Regimen
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
D/C/F/TAF
Intervention Description
Once-daily single-tablet regimen containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg.
Intervention Type
Drug
Intervention Name(s)
Boosted Protease Inhibitor (bPI)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
FTC/TDF
Intervention Description
Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF).
Primary Outcome Measure Information:
Title
Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 48
Description
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.
Time Frame
Through Week 48
Secondary Outcome Measure Information:
Title
Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=20 Copies/mL) Cumulative Through 48 Weeks
Description
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.
Time Frame
Through 48 Weeks
Title
Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=200 Copies/mL) Cumulative Through 48 Weeks
Description
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.
Time Frame
Through 48 Weeks
Title
Percentage of Participants With Non-Virologic Rebound at Week 48 by Kaplan-Meier Estimates
Description
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). Here Kaplan-Meier estimates percentage of participants with non-virologic rebound at week 48.
Time Frame
Baseline up to Week 48
Title
Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through Week 48
Description
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.
Time Frame
Up to Week 48
Title
Change From Baseline in Serum Creatinine Levels at Weeks 24 and 48
Description
Change from baseline in serum creatinine levels at Weeks 24 and 48 was assessed.
Time Frame
Baseline and Weeks 24 and 48
Title
Change From Baseline in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Weeks 24 and 48
Description
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).
Time Frame
Baseline, Weeks 24 and 48
Title
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
Description
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.
Time Frame
Baseline, Weeks 24 and 48
Title
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
Description
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).
Time Frame
Baseline, Weeks 24 and 48
Title
Change From Baseline in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR) at Weeks 24 and 48
Description
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.
Time Frame
Baseline, Weeks 24 and 48
Title
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
Description
Change from baseline in URBPCR and UB2MGCR was assessed at Weeks 24 and 48. Retinol binding protein is a marker of proximal tubular function.
Time Frame
Baseline, Weeks 24 and 48
Title
Percent Change From Baseline in Urine Fractional Excretion of Phosphate (FEPO4) at Weeks 24 and 48
Description
Percent change from baseline in urine FEPO4 was assessed at Weeks 24 and 48.
Time Frame
Baseline, Weeks 24 and 48
Title
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
Description
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).
Time Frame
Week 48
Title
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
Description
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.
Time Frame
Week 48
Title
Change From Baseline in Cluster of Differentiation 4 Plus (CD4+) Cell Count at Weeks 24 and 48
Description
Change from baseline in CD4+ cell count was assessed at Weeks 24 and 48.
Time Frame
Baseline, Weeks 24 and 48
Title
Percentage of Participants With Treatment Adherence of Greater Than (>)95 Percent (%) (Approach 1) Through Week 48
Description
Treatment adherence (defined as adherence of >95%) was assessed by the drug accountability cumulative through Week 48 (Approach 1).
Time Frame
Through Week 48
Title
Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 48
Description
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).
Time Frame
Through Week 48
Title
Number of Participants With Resistance to Study Drug
Description
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 >=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.
Time Frame
Up to Week 48
Title
Predose (Trough) Plasma Concentration (C0h) of Darunavir
Description
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.
Time Frame
Predose at Weeks 2, 4, 8, 12, 24, 36, and 48
Title
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
Description
Percent change from baseline in bone biomarkers: P1NP and CTX was assessed at Weeks 24 and 48.
Time Frame
Baseline, Weeks 24 and 48
Title
Percent Change From Baseline in Parathyroid Hormone (PTH) at Weeks 24 and 48
Description
Percent change from baseline in bone biomarker: PTH was assessed at Weeks 24 and 48.
Time Frame
Baseline, Weeks 24 and 48
Title
Percent Change From Baseline in 25-hydroxy Vitamin D at Weeks 24 and 48
Description
Percent change from baseline in bone biomarker: 25-hydroxy vitamin D was assessed at Weeks 24 and 48.
Time Frame
Baseline, Weeks 24 and 48
Title
Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24 and 48
Description
Percent change from baseline in spine and hip BMD was assessed at Weeks 24 and 48.
Time Frame
Baseline, Weeks 24 and 48
Title
Change From Baseline in Bone Mineral Density (BMD) T-Score at Weeks 24 and 48
Description
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.
Time Frame
Baseline, Weeks 24 and 48
Title
Percentage of Participants With Virologic Rebound (HIV-1 RNA >=20 Copies/mL) Cumulative Through Week 96
Description
Virologic rebound was defined as: confirmed plasma HIV-1 RNA level >=20 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA >=20 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA >=20 copies/mL at the study cutoff of Week 96 (that is, any last viral load [re]test having occurred no later than 6 weeks after Week 96). Percentage of participants with virologic rebound were reported.
Time Frame
Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Title
Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 96
Description
Virologic rebound was defined as: confirmed plasma HIV-1 RNA level >=50 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA >=50 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA >=50copies/mL at the study cutoff of Week 96 (that is, any last viral load [re]test having occurred no later than 6 weeks after Week 96). Percentage of participants with virologic rebound were reported.
Time Frame
Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Title
Percentage of Participants With Virologic Rebound (HIV-1 RNA >=200 Copies/mL) Cumulative Through Week 96
Description
Virologic rebound was defined as: confirmed plasma HIV-1 RNA level >=200 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA >=200 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA >=200 copies/mL at the study cutoff of Week 96 (that is, any last viral load [re]test having occurred no later than 6 weeks after Week 96). Percentage of participants with virologic rebound were reported.
Time Frame
Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Title
Percentage of Participants With Non-Virologic Rebound at Week 96 by Kaplan-Meier Estimates
Description
Here Kaplan-Meier estimates percentage of participants with non-virologic rebound at Week 96.
Time Frame
Baseline to Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Title
Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach
Description
Percentage of participants with virologic response based on HIV-1 RNA <20, <50, and <200 copies/mL threshold were analyzed at Week 96 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic response was defined as having last available HIV-1 RNA <20/50/200 copies/mL (observed case).
Time Frame
Week 96 (Comprising up to Week 96 for D/C/F/TAF and 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52 up to Week 96])
Title
Percentage of Participants With Virologic Response Based on HIV-1 RNA <20, <50, and <200 Copies/mL Threshold at Week 96 as Defined by the TLOVR Algorithm
Description
Percentage of participants with virologic response based on HIV-1 RNA <20, <50, and <200 copies/mL threshold were analyzed at Week 96 using TLOVR algorithm approach. TLOVR was defined as sustained HIV-1 RNA <20/50/200 copies/mL.
Time Frame
Week 96 (Comprising up to Week 96 for D/C/F/TAF and 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52 up to Week 96])
Title
Percentage of Participants With Virologic Failure Based on HIV-1 RNA >=20, >=50, and >=200 Copies/mL Threshold at Week 96 as Defined by the FDA Snapshot Approach
Description
Percentage of participants with virologic failure based on HIV-1 RNA >=20, >=50, and >=200 copies/mL threshold were analyzed at Week 96 using FDA snapshot approach. FDA Snapshot approach analysis was based on the last observed viral load data: virologic failure was defined by the FDA snapshot approach as having last available HIV-1 RNA >=20/50/200 copies/mL at Week 96; virologic failure - leading to discontinuation; virologic failure - discontinued due to other reason and last available HIV-1 RNA >=20/50/200 copies/mL.
Time Frame
Week 96 (Comprising up to Week 96 for D/C/F/TAF and 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52 up to Week 96])
Title
Change From Reference in CD4+ Cell Count at Week 96
Description
Change from reference in CD4+ cell count was assessed at Week 96. The change from reference in CD4+ count at a given time point is defined as: CD4+ at a given time point minus reference CD4+. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF (Comprising 44 weeks of D/C/F/TAF exposure [that is, from the switch to D/C/F/TAF at Week 52])
Title
Number of Participants With Resistance to Study Drug Through Week 96
Description
HIV-1 genotypes were analyzed from samples of participants with confirmed virologic rebound in case they had HIV-1 RNA values >=400 copies/mL at failure or at later time points, including participants who discontinued with last HIV-1 RNA >=400 copies/mL. Virologic rebound was defined as: confirmed plasma HIV-1 RNA level >=20 copies/mL up to and including Week 96, last available on-treatment (single) HIV-1 RNA >=20 copies/mL at premature discontinuation (irrespective of reason), and last available on-treatment HIV-1 RNA >=20 copies/mL at the study cutoff of Week 96 (that is, any last viral load [re]test having occurred no later than 6 weeks after Week 96). Number of participants who developed resistance to any of the study drug (DRV, FTC, and TFV/TAF) were reported.
Time Frame
Through Week 96 (D/C/F/TAF arm), up to Week 48 (Control arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Title
Percentage of Participants With Treatment Adherence of >95 (Approach 1) Through Week 96
Description
Treatment adherence (defined as adherence of >95%) was assessed by the drug accountability cumulative through Week 96 (Approach 1).
Time Frame
Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Title
Percentage of Participants With Treatment Adherence of >95% (Approach 2) Through Week 96
Description
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 96, whichever came sooner (Approach 2).
Time Frame
Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Title
Percentage of Participants Experiencing Grade 3 and Grade 4 AEs, SAEs, and Premature Discontinuation Due to AEs Through Week 96
Description
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. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Time Frame
Through Week 96 (D/C/F/TAF arm) and from Week 52 to Week 96 (Switch to D/C/F/TAF arm)
Title
Change From Reference in Serum Creatinine Levels at Week 96
Description
Change from reference in serum creatinine levels at Week 96 was assessed. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (eGFRcr, by Cockcroft-Gault Formula [eGFRcg]) at Week 96
Description
Change from reference in eGFRcr (by Cockcroft-Gault formula) was assessed at Week 96. 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). For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Creatinine (by CKD-EPI) at Week 96
Description
Change from reference in eGFRcr (by CKD-EPI) was assessed at Week 96. 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*0.993^age; 2) Scr greater than (>)0.7 mg/dL: 144*(Scr/0.7)^-1.209*0.993^age. Male: 1) Scr <=0.9 mg/dL: 141*(Scr/0.9)^-0.411*0.993^age; 2) Scr >0.9 mg/dL: 141*(Scr/0.9)^-1.209*0.993^age. . For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Change From Reference in Estimated Glomerular Filtration Rate Based on Serum Cystatin C (by CKD-EPI) at Week 96
Description
Change from reference in eGFRcyst (by CKD-EPI) was assessed at Week 96. eGFRcyst according to the CKD-EPI formula - 1) Serum Cystatin C (Scyst) <=0.8 mg/L: 133*(Scyst/0.8)^-0.499*0.996^age (*0.932 if female); 2) Scyst >0.8 mg/L: 133*(Scyst/0.8)^-1.328*0.996^age (*0.932 if female). For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Change From Reference in UACR at Week 96
Description
Change from reference in UACR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Change From Reference in URBPCR at Week 96
Description
Change from reference in URBPCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Change From Reference in UPCR at Week 96
Description
Change from reference in UPCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Change From Reference in UB2MGCR at Week 96
Description
Change from reference in UB2MGCR was assessed at Week 96. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Percent Change From Reference in FEPO4 at Week 96
Description
Percent change from reference in FEPO4 at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ F/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Percent Change From Reference in Levels of Serum P1NP at Week 96
Description
Percent change from reference in serum P1NP levels at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Percent Change From Reference in Levels of Serum CTX at Week 96
Description
Percent change from reference in serum CTX at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Percent Change From Reference in Levels of PTH at Week 96
Description
Percent change from reference in PTH at Week 96 was reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Percent Change From Reference in Levels of 25-OH Vitamin D at Week 96
Description
Percent change from reference in 25-OH Vitamin D at Week 96 were reported. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Percent Change From Reference in Hip and Spine BMD at Week 96
Description
The BMD is the amount of mineral in gram per square centimeter of bone, which was assessed by DXA scan. Positive values are "best values" and negative values are "worst values" of change. Percent change from reference in hip and spine BMD was assessed. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Change From Reference in BMD T-score of Hip and Spine at Week 96
Description
BMD status was assessed using BMD T-scores; normal bone status was defined by a BMD T-score >= -1, osteopenia by a T-score >= -2.5 to <-1.0, and osteoporosis by a T-score <-2.5. For the D/C/F/TAF group, reference is the comparative treatment phase baseline as in Week 48 analysis (Reference 1). For the Switch to D/C/F/TAF (late switch) group, the last value prior to the switch was used as reference (reference 2).
Time Frame
From Reference 1 to Week 96 for D/C/F/TAF+ FTC/TDF Group and Reference 2 to Week 96 for Switch to D/C/F/TAF
Title
Percentage of Participants With Non-Virologic Rebound by Kaplan-Meier Estimates
Description
Virologic rebound is defined as participants who show confirmed HIV-1 RNA >=50 copies/mL, or for which the last available (single) HIV-1 RNA value on treatment was >=50 copies/mL. Here, Kaplan-Meier estimates (%) of non-virologic rebound at every 6 months interval are presented.
Time Frame
Week 96 to end of extension (at every 6 months, up to 42 months)
Title
Percentage of Participants With Non-Treatment Failure by Kaplan-Meier Estimates
Description
Percentage of participants with non-treatment failure by Kaplan-Meier Estimates were reported. Treatment failure was defined as having either protocol-defined virologic rebound or having discontinued for reasons other than alternate access to D/C/F/TAF (or other antiretroviral [ARV]).
Time Frame
Week 96 to end of extension (up to 42 months)
Title
Percentage of Participants With HIV RNA <50, <20, <200 Copies/mL Post Week 96 to End of Extension
Description
Percentage of participants with HIV RNA <50, <20, <200 copies/mL post Week 96 to end of extension were reported.
Time Frame
Week 96 to end of extension (up to 42 months)
Title
CD4+ Cell Count Post-Week 96 to End of Extension
Description
The immunologic change was determined by Cluster of CD4+ cell count. CD4+ cell count post-Week 96 to end of extension were assessed.
Time Frame
Week 96 to end of extension (up to 42 months)
Title
Percentage of Participants With Treatment Adherence of >95% From Week 96 to End of Extension
Description
Treatment adherence (defined as adherence of >95%) was assessed by the drug accountability and was calculated cumulative from start of treatment/switch to last study drug intake by determination of the cumulative treatment adherence in participants who returned all dispensed bottles prior to or at the last visit in the study from Week 96 to end of extension.
Time Frame
Week 96 to end of extension (up to 42 months)
Title
Percentage of Participants Experiencing Grade 3 and 4 AEs, Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Post-Week 96 to End of Extension
Description
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. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Time Frame
From Week 96 to end of extension (up to 42 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen R&D Ireland Clinical Trial
Organizational Affiliation
Janssen R&D Ireland
Official's Role
Study Director
Facility Information:
City
Phoenix
State/Province
Arizona
Country
United States
City
Bakersfield
State/Province
California
Country
United States
City
Beverly Hills
State/Province
California
Country
United States
City
Long Beach
State/Province
California
Country
United States
City
Los Angeles
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
San Francisco
State/Province
California
Country
United States
City
Washington
State/Province
District of Columbia
Country
United States
City
Fort Lauderdale
State/Province
Florida
Country
United States
City
Fort Pierce
State/Province
Florida
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
West Palm Beach
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Savannah
State/Province
Georgia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Springfield
State/Province
Massachusetts
Country
United States
City
Berkley
State/Province
Michigan
Country
United States
City
Detroit
State/Province
Michigan
Country
United States
City
Minneapolis
State/Province
Minnesota
Country
United States
City
Kansas City
State/Province
Missouri
Country
United States
City
Saint Louis
State/Province
Missouri
Country
United States
City
Hillsborough
State/Province
New Jersey
Country
United States
City
Newark
State/Province
New Jersey
Country
United States
City
Somers Point
State/Province
New Jersey
Country
United States
City
Santa Fe
State/Province
New Mexico
Country
United States
City
New York
State/Province
New York
Country
United States
City
Chapel Hill
State/Province
North Carolina
Country
United States
City
Winston-Salem
State/Province
North Carolina
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Providence
State/Province
Rhode Island
Country
United States
City
Austin
State/Province
Texas
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Fort Worth
State/Province
Texas
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Longview
State/Province
Texas
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Antwerpen
Country
Belgium
City
Brussels
Country
Belgium
City
Bruxelles
Country
Belgium
City
Gent
Country
Belgium
City
Leuven
Country
Belgium
City
Liège
Country
Belgium
City
Edmonton
State/Province
Alberta
Country
Canada
City
Vancouver
State/Province
British Columbia
Country
Canada
City
Toronto
State/Province
Ontario
Country
Canada
City
Montreal
State/Province
Quebec
Country
Canada
City
Le Kremlin Bicetre
Country
France
City
Lyon
Country
France
City
Marseille
Country
France
City
Montpellier
Country
France
City
Nantes
Country
France
City
Paris Cedex 10
Country
France
City
Paris Cedex 12
Country
France
City
Paris
Country
France
City
Strasbourg Cedex
Country
France
City
Tourcoing
Country
France
City
Bydgoszcz
Country
Poland
City
Chorzow
Country
Poland
City
Lodz
Country
Poland
City
Warszawa
Country
Poland
City
Wroclaw
Country
Poland
City
San Juan
Country
Puerto Rico
City
Alicante
Country
Spain
City
Badalona
Country
Spain
City
Barcelona
Country
Spain
City
Cordoba
Country
Spain
City
Elche
Country
Spain
City
Madrid
Country
Spain
City
San Sebastian
Country
Spain
City
Sevilla
Country
Spain
City
Valencia
Country
Spain
City
Göteborg
Country
Sweden
City
Malmö
Country
Sweden
City
Stockholm
Country
Sweden
City
Basel
Country
Switzerland
City
Bern
Country
Switzerland
City
Zurich N/a
Country
Switzerland
City
Brighton
Country
United Kingdom
City
London
Country
United Kingdom
City
Manchester
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
34100149
Citation
Ackaert O, McDougall D, Perez-Ruixo C, Perez-Ruixo JJ, Jezorwski J, Crauwels HM. Population Pharmacokinetic Analysis of Darunavir and Tenofovir Alafenamide in HIV-1-Infected Patients on the Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen (AMBER and EMERALD Studies). AAPS J. 2021 Jun 7;23(4):82. doi: 10.1208/s12248-021-00607-8.
Results Reference
derived
PubMed Identifier
33528318
Citation
Huhn GD, Wilkin A, Mussini C, Spinner CD, Jezorwski J, El Ghazi M, Van Landuyt E, Lathouwers E, Brown K, Baugh B; AMBER and EMERALD study groups. Week 96 subgroup analyses of the phase 3, randomized AMBER and EMERALD trials evaluating the efficacy and safety of the once daily darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) single-tablet regimen in antiretroviral treatment (ART)-naive and -experienced, virologically-suppressed adults living with HIV-1. HIV Res Clin Pract. 2020 Dec;21(6):151-167. doi: 10.1080/25787489.2020.1844520. Epub 2021 Feb 2.
Results Reference
derived
PubMed Identifier
31516033
Citation
Lathouwers E, Wong EY, Brown K, Baugh B, Ghys A, Jezorwski J, Mohsine EG, Van Landuyt E, Opsomer M, De Meyer S; AMBER and EMERALD Study Groups. Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials. AIDS Res Hum Retroviruses. 2020 Jan;36(1):48-57. doi: 10.1089/AID.2019.0111. Epub 2019 Oct 21.
Results Reference
derived
PubMed Identifier
31464642
Citation
Huhn GD, Eron JJ, Girard PM, Orkin C, Molina JM, DeJesus E, Petrovic R, Luo D, Van Landuyt E, Lathouwers E, Nettles RE, Brown K, Wong EY. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-experienced, virologically suppressed patients with HIV-1: subgroup analyses of the phase 3 EMERALD study. AIDS Res Ther. 2019 Aug 29;16(1):23. doi: 10.1186/s12981-019-0235-1.
Results Reference
derived
PubMed Identifier
28993180
Citation
Orkin C, Molina JM, Negredo E, Arribas JR, Gathe J, Eron JJ, Van Landuyt E, Lathouwers E, Hufkens V, Petrovic R, Vanveggel S, Opsomer M; EMERALD study group. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial. Lancet HIV. 2018 Jan;5(1):e23-e34. doi: 10.1016/S2352-3018(17)30179-0. Epub 2017 Oct 6.
Results Reference
derived
Learn more about this trial
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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