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Safety and Efficacy of Switching From Regimens Consisting of Boosted Atazanavir or Darunavir Plus Either Emtricitabine/Tenofovir or Abacavir/Lamivudine to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Infected Adults

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ClinicalTrials.gov Identifier: NCT02603107
Recruitment Status : Active, not recruiting
First Posted : November 11, 2015
Results First Posted : June 5, 2018
Last Update Posted : May 23, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV-1 Infection
Interventions Drug: RTV
Drug: ATV
Drug: DRV
Drug: COBI
Drug: ATV/co
Drug: DRV/co
Drug: FTC/TDF
Drug: ABC/3TC
Drug: B/F/TAF
Enrollment 578
Recruitment Details Participants were enrolled at study sites in North America, Australia, and Europe. The first participant was screened on 20 November 2015. The last Week 48 study visit occurred on 15 May 2017.
Pre-assignment Details 707 participants were screened.
Arm/Group Title B/F/TAF Stay on Baseline Regimen (SBR)
Hide Arm/Group Description

Randomized Phase: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed-dose combination (FDC) tablet orally once daily for at least 48 weeks, without regard to food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks.

Randomized Phase: Participants remained on current antiretroviral (ARV) regimen consisting of ritonavir (RTV)-boosted or cobicistat (COBI)-boosted atazanavir (ATV) or darunavir (DRV), plus either emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) (200/300 mg) FDC tablet or abacavir/lamivudine (ABC/3TC) (600/300 mg) FDC tablet administered orally once daily for at least 48 weeks with food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks.

Period Title: Randomized Phase
Started 290 288
Completed 245 240
Not Completed 45 48
Reason Not Completed
Randomized and Never Treated             0             1
Still in Study             32             27
Adverse Event             2             0
Death             1             1
Investigator's Discretion             0             1
Non-Compliance with Study Drug             1             1
Protocol Violation             1             0
Withdrew Consent             8             14
Lost to Follow-up             0             3
Period Title: Optional Extension Phase
Started 241 [1] 213 [2]
Completed 0 0
Not Completed 241 213
Reason Not Completed
Still in Study             241             213
[1]
4 participants who completed the Randomized Phase did not continue in the Optional Extension Phase.
[2]
27 participants who completed the Randomized Phase did not continue in the Optional Extension Phase.
Arm/Group Title B/F/TAF Stay on Baseline Regimen (SBR) Total
Hide Arm/Group Description

Randomized Phase: B/F/TAF (50/200/25 mg) FDC tablet administered orally once daily for at least 48 weeks without regard to food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks.

Randomized Phase: Participants remained on current ARV regimen consisting of RTV or COBI boosted ATV or DRV, plus either FTC/TDF (200/300 mg) FDC tablets or ABC/3TC (600/300 mg) FDC tablet administered orally once daily for at least 48 weeks with food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks.

Total of all reporting groups
Overall Number of Baseline Participants 290 287 577
Hide Baseline Analysis Population Description
Safety Analysis Set: all randomized participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 290 participants 287 participants 577 participants
47  (10.5) 46  (10.5) 46  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 287 participants 577 participants
Female
47
  16.2%
53
  18.5%
100
  17.3%
Male
243
  83.8%
234
  81.5%
477
  82.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 287 participants 577 participants
American Indian or Alaska Native
3
   1.0%
3
   1.0%
6
   1.0%
Asian
6
   2.1%
10
   3.5%
16
   2.8%
Black
79
  27.2%
72
  25.1%
151
  26.2%
Native Hawaiian or Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
White
188
  64.8%
190
  66.2%
378
  65.5%
Other
14
   4.8%
12
   4.2%
26
   4.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 287 participants 577 participants
Hispanic or Latino
60
  20.7%
47
  16.4%
107
  18.5%
Not Hispanic or Latino
230
  79.3%
240
  83.6%
470
  81.5%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 287 participants 577 participants
Australia
15
   5.2%
16
   5.6%
31
   5.4%
Canada
18
   6.2%
15
   5.2%
33
   5.7%
Belgium
2
   0.7%
3
   1.0%
5
   0.9%
France
17
   5.9%
17
   5.9%
34
   5.9%
Germany
28
   9.7%
33
  11.5%
61
  10.6%
Italy
3
   1.0%
5
   1.7%
8
   1.4%
Spain
6
   2.1%
4
   1.4%
10
   1.7%
United Kingdom
31
  10.7%
23
   8.0%
54
   9.4%
United States
166
  57.2%
164
  57.1%
330
  57.2%
Dominican Republic
4
   1.4%
7
   2.4%
11
   1.9%
HIV-1 RNA Category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 287 participants 577 participants
< 50 copies/mL
285
  98.3%
277
  96.5%
562
  97.4%
≥ 50 copies/mL
5
   1.7%
10
   3.5%
15
   2.6%
CD4 Cell Count  
Mean (Standard Deviation)
Unit of measure:  cells/μL
Number Analyzed 290 participants 287 participants 577 participants
669  (303.4) 657  (285.0) 663  (294.2)
CD4 Cell Count Category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 287 participants 577 participants
< 50 cells/μL
0
   0.0%
0
   0.0%
0
   0.0%
≥ 50 to < 200 cells/μL
4
   1.4%
8
   2.8%
12
   2.1%
≥ 200 to < 350 cells/μL
26
   9.0%
30
  10.5%
56
   9.7%
≥ 350 to < 500 cells/μL
62
  21.4%
60
  20.9%
122
  21.1%
≥ 500 cells/μL
198
  68.3%
189
  65.9%
387
  67.1%
HIV Disease Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 287 participants 577 participants
Asymptomatic
240
  82.8%
234
  81.5%
474
  82.1%
Symptomatic HIV Infection
16
   5.5%
20
   7.0%
36
   6.2%
Acquired Immunodeficiency Syndrome (AIDS)
34
  11.7%
33
  11.5%
67
  11.6%
Prior ARV Regimen  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 287 participants 577 participants
Boosted ATV + ABC/3TC
21
   7.2%
23
   8.0%
44
   7.6%
Boosted DRV + ABC/3TC
24
   8.3%
21
   7.3%
45
   7.8%
Boosted ATV + FTC/TDF
105
  36.2%
110
  38.3%
215
  37.3%
Boosted DRV + FTC/TDF
140
  48.3%
133
  46.3%
273
  47.3%
1.Primary Outcome
Title Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm
Hide Description The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all participants who were randomized into the study and received at least 1 dose of study drug.
Arm/Group Title B/F/TAF Stay on Baseline Regimen (SBR)
Hide Arm/Group Description:

Randomized Phase: B/F/TAF (50/200/25 mg) FDC tablet administered orally once daily for at least 48 weeks without regard to food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks.

Randomized Phase: Participants remained on current ARV regimen consisting of RTV or COBI boosted ATV or DRV, plus either FTC/TDF (200/300 mg) FDC tablet or ABC/3TC (600/300 mg) FDC tablet administered orally once daily for at least 48 weeks with food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks.

Overall Number of Participants Analyzed 290 287
Measure Type: Number
Unit of Measure: percentage of participants
1.7 1.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection B/F/TAF, Stay on Baseline Regimen (SBR)
Comments The null hypothesis was that the percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 in the B/F/TAF group was at least 4% higher than the rate in the SBR group; the alternative hypothesis was that the percentage of participants with HIV-1 RNA ≥ 50 copies/mL in the B/F/TAF group was less than 4% higher than that in the SBR group.
Type of Statistical Test Non-Inferiority
Comments A sample size of 520 participants (260 participants per treatment group) would provide at least 90% power to establish a non-inferiority margin of 4% in the Week 48 response rate (HIV-1 RNA ≥ 50 copies/mL) between the 2 treatment groups. Sample size was based on the assumptions that both treatment groups have 2% of participants with HIV-1 RNA ≥ 50 copies/mL (based on Gilead Genvoya and Stribild studies) and that the significance level of the test is at a 1-sided 0.025 level.
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value -0.0
Confidence Interval (2-Sided) 95.002%
-2.5 to 2.5
Estimation Comments The difference in percentages and its 95.002% confidence interval (CI) were calculated based on an unconditional exact method using 2 inverted 1-sided tests.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection B/F/TAF, Stay on Baseline Regimen (SBR)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm
Hide Description The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title B/F/TAF Stay on Baseline Regimen (SBR)
Hide Arm/Group Description:

Randomized Phase: B/F/TAF (50/200/25 mg) FDC tablet administered orally once daily for at least 48 weeks without regard to food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks.

Randomized Phase: Participants remained on current ARV regimen consisting of RTV or COBI boosted ATV or DRV, plus either FTC/TDF (200/300 mg) FDC tablet or ABC/3TC (600/300 mg) FDC tablet administered orally once daily for at least 48 weeks with food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks.

Overall Number of Participants Analyzed 290 287
Measure Type: Number
Unit of Measure: percentage of participants
92.1 88.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection B/F/TAF, Stay on Baseline Regimen (SBR)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments The non-inferiority of B/F/TAF would be established if the lower bound of the 2-sided 95.002% CI of the difference between the treatmnet groups (B/F/TAF group - SBR group) in the percentage of participants with HIV-1 RNA < 50 copies/mL is greater than -10%.
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 3.2
Confidence Interval (2-Sided) 95.002%
-1.6 to 8.2
Estimation Comments The difference in percentages and its 95.002% confidence interval (CI) were calculated based on an unconditional exact method using 2 inverted 1-sided tests.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection B/F/TAF, Stay on Baseline Regimen (SBR)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.20
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in CD4 Cell Count at Week 48
Hide Description [Not Specified]
Time Frame Baseline to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title B/F/TAF Stay on Baseline Regimen (SBR)
Hide Arm/Group Description:

Randomized Phase: B/F/TAF (50/200/25 mg) FDC tablet administered orally once daily for at least 48 weeks without regard to food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks.

Randomized Phase: Participants remained on current ARV regimen consisting of RTV or COBI boosted ATV or DRV, plus either FTC/TDF (200/300 mg) FDC tablet or ABC/3TC (600/300 mg) FDC tablet administered orally once daily for at least 48 weeks with food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks.

Overall Number of Participants Analyzed 265 256
Mean (Standard Deviation)
Unit of Measure: cells/μL
25  (151.2) 0  (159.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection B/F/TAF, Stay on Baseline Regimen (SBR)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.068
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Least Squares Means (LSM)
Estimated Value 25
Confidence Interval (2-Sided) 95%
-2 to 52
Estimation Comments [Not Specified]
Time Frame Up to the Week 48 Data Cut
Adverse Event Reporting Description Safety Analysis Set: all participants who were randomized into the study and received at least 1 dose of study drug.
 
Arm/Group Title B/F/TAF Stay on Baseline Regimen (SBR)
Hide Arm/Group Description

Randomized Phase: B/F/TAF (50/200/25 mg) FDC tablet administered orally once daily for at least 48 weeks without regard to food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks.

Randomized Phase: Participants remained on current ARV regimen consisting of RTV or COBI boosted ATV or DRV, plus either FTC/TDF (200/300 mg) FDC tablet or ABC/3TC (600/300 mg) FDC tablet administered orally once daily for at least 48 weeks with food.

Extension Phase: After Week 48, participants in countries where B/F/TAF is not available will be given the option to receive B/F/TAF for up to 96 additional weeks.

All-Cause Mortality
B/F/TAF Stay on Baseline Regimen (SBR)
Affected / at Risk (%) Affected / at Risk (%)
Total   1/290 (0.34%)   1/287 (0.35%) 
Show Serious Adverse Events Hide Serious Adverse Events
B/F/TAF Stay on Baseline Regimen (SBR)
Affected / at Risk (%) Affected / at Risk (%)
Total   17/290 (5.86%)   20/287 (6.97%) 
Cardiac disorders     
Acute myocardial infarction  1  1/290 (0.34%)  1/287 (0.35%) 
Atrial fibrillation  1  0/290 (0.00%)  1/287 (0.35%) 
Coronary artery stenosis  1  1/290 (0.34%)  1/287 (0.35%) 
Myocardial infarction  1  0/290 (0.00%)  1/287 (0.35%) 
Sinus node dysfunction  1  1/290 (0.34%)  0/287 (0.00%) 
Eye disorders     
Optic disc disorder  1  1/290 (0.34%)  0/287 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  0/290 (0.00%)  1/287 (0.35%) 
Anal fistula  1  0/290 (0.00%)  1/287 (0.35%) 
Diarrhoea  1  0/290 (0.00%)  1/287 (0.35%) 
Diverticular perforation  1  0/290 (0.00%)  1/287 (0.35%) 
Enterocutaneous fistula  1  0/290 (0.00%)  1/287 (0.35%) 
Lower gastrointestinal haemorrhage  1  0/290 (0.00%)  1/287 (0.35%) 
General disorders     
Chest pain  1  1/290 (0.34%)  1/287 (0.35%) 
Hepatobiliary disorders     
Hepatitis acute  1  0/290 (0.00%)  1/287 (0.35%) 
Infections and infestations     
Acute hepatitis C  1  1/290 (0.34%)  0/287 (0.00%) 
Anal abscess  1  0/290 (0.00%)  1/287 (0.35%) 
Appendicitis  1  0/290 (0.00%)  1/287 (0.35%) 
Cellulitis  1  1/290 (0.34%)  0/287 (0.00%) 
Diverticulitis  1  0/290 (0.00%)  1/287 (0.35%) 
Hepatitis A  1  2/290 (0.69%)  0/287 (0.00%) 
Hepatitis C  1  0/290 (0.00%)  1/287 (0.35%) 
Localised infection  1  0/290 (0.00%)  1/287 (0.35%) 
Pneumonia  1  1/290 (0.34%)  0/287 (0.00%) 
Pyelonephritis  1  1/290 (0.34%)  0/287 (0.00%) 
Stoma site abscess  1  0/290 (0.00%)  1/287 (0.35%) 
Upper respiratory tract infection  1  1/290 (0.34%)  0/287 (0.00%) 
Injury, poisoning and procedural complications     
Acetabulum fracture  1  0/290 (0.00%)  1/287 (0.35%) 
Head injury  1  0/290 (0.00%)  1/287 (0.35%) 
Joint dislocation  1  1/290 (0.34%)  0/287 (0.00%) 
Musculoskeletal and connective tissue disorders     
Osteoarthritis  1  1/290 (0.34%)  0/287 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Anogenital warts  1  0/290 (0.00%)  1/287 (0.35%) 
Bladder neoplasm  1  0/290 (0.00%)  1/287 (0.35%) 
Brain cancer metastatic  1  1/290 (0.34%)  0/287 (0.00%) 
Lung neoplasm malignant  1  1/290 (0.34%)  0/287 (0.00%) 
Nervous system disorders     
Cervical radiculopathy  1  1/290 (0.34%)  0/287 (0.00%) 
Metabolic encephalopathy  1  1/290 (0.34%)  0/287 (0.00%) 
Thrombotic stroke  1  0/290 (0.00%)  1/287 (0.35%) 
Pregnancy, puerperium and perinatal conditions     
Foetal death  1  0/290 (0.00%)  1/287 (0.35%) 
Psychiatric disorders     
Anxiety  1  0/290 (0.00%)  1/287 (0.35%) 
Schizoaffective disorder  1  1/290 (0.34%)  0/287 (0.00%) 
Schizophrenia  1  1/290 (0.34%)  1/287 (0.35%) 
Suicide attempt  1  0/290 (0.00%)  1/287 (0.35%) 
Renal and urinary disorders     
Acute kidney injury  1  0/290 (0.00%)  1/287 (0.35%) 
Ureteric stenosis  1  0/290 (0.00%)  1/287 (0.35%) 
Ureterolithiasis  1  1/290 (0.34%)  0/287 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  1/290 (0.34%)  0/287 (0.00%) 
Vascular disorders     
Hypovolaemic shock  1  0/290 (0.00%)  1/287 (0.35%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
B/F/TAF Stay on Baseline Regimen (SBR)
Affected / at Risk (%) Affected / at Risk (%)
Total   98/290 (33.79%)   98/287 (34.15%) 
Gastrointestinal disorders     
Diarrhoea  1  24/290 (8.28%)  17/287 (5.92%) 
Infections and infestations     
Nasopharyngitis  1  21/290 (7.24%)  34/287 (11.85%) 
Upper respiratory tract infection  1  20/290 (6.90%)  22/287 (7.67%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  12/290 (4.14%)  15/287 (5.23%) 
Back pain  1  13/290 (4.48%)  17/287 (5.92%) 
Nervous system disorders     
Headache  1  35/290 (12.07%)  12/287 (4.18%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Name/Title: Gilead Clinical Study Information Center
Organization: Gilead Sciences
Phone: 1-833-445-3230 (GILEAD-0)
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02603107     History of Changes
Other Study ID Numbers: GS-US-380-1878
2015-004011-20 ( EudraCT Number )
First Submitted: November 10, 2015
First Posted: November 11, 2015
Results First Submitted: May 3, 2018
Results First Posted: June 5, 2018
Last Update Posted: May 23, 2019