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Switching to a Fixed Dose Combination of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) in HIV-1 Infected Adults Who Are Virologically Suppressed

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ClinicalTrials.gov Identifier: NCT03110380
Recruitment Status : Active, not recruiting
First Posted : April 12, 2017
Results First Posted : November 20, 2019
Last Update Posted : December 22, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition HIV-1-infection
Interventions Drug: B/F/TAF
Drug: F/TAF
Drug: DTG
Drug: DTG Placebo
Drug: F/TAF Placebo
Drug: B/F/TAF Placebo
Enrollment 567
Recruitment Details Participants were enrolled at study sites in North America and Europe. The first participant was screened on 12 June 2017. The last Week 48 study visit occurred on 04 December 2018.
Pre-assignment Details 633 participants were screened.
Arm/Group Title B/F/TAF DTG + F/TAF
Hide Arm/Group Description

Double-Blind Phase: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) fixed-dose combination (FDC) tablet + dolutegravir (DTG) placebo tablet + emtricitabine/tenofovir alafenamide (F/TAF) placebo tablet administered orally once daily without regard to food for 48 weeks.

Open-Label Extension Phase: After Week 48, participants continued to take their blinded study drug and attended visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants in a country where B/F/TAF FDC was not available was given the option to receive open-label B/F/TAF for up to 96 weeks, or until the product became accessible through an access program, or until Gilead elected to discontinue the study in that country, whichever occurred first.

Double-Blind Phase: DTG 50 mg tablet + F/TAF (200/25 mg) FDC tablet + B/F/TAF placebo tablet administered orally once daily without regard to food for 48 weeks.

Open-Label Extension Phase: After Week 48, participants continued to take their blinded study drug and attended visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants in a country where B/F/TAF FDC was not available was given the option to receive open-label B/F/TAF for up to 96 weeks, or until the product became accessible through an access program, or until Gilead elected to discontinue the study in that country, whichever occurred first.

Period Title: Overall Study
Started 284 283
Completed 0 0
Not Completed 284 283
Reason Not Completed
Randomized and Never Treated             0             2
Still in Study             264             256
Adverse Event             3             3
Death             2             1
Investigator's Discretion             1             2
Non-Compliance with Study Drug             1             1
Protocol Violation             0             1
Withdrew Consent             9             16
Lost to Follow-up             4             1
Arm/Group Title B/F/TAF DTG + F/TAF Total
Hide Arm/Group Description B/F/TAF (50/200/25 mg) FDC tablet + DTG placebo tablet + F/TAF placebo tablet administered orally once daily without regard to food for 48 weeks. DTG 50 mg tablet + F/TAF (200/25 mg) FDC tablet + B/F/TAF placebo tablet administered orally once daily without regard to food for 48 weeks. Total of all reporting groups
Overall Number of Baseline Participants 284 281 565
Hide Baseline Analysis Population Description
The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 284 participants 281 participants 565 participants
50  (11.3) 49  (11.3) 50  (11.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 284 participants 281 participants 565 participants
Female 39 41 80
Male 245 240 485
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 284 participants 281 participants 565 participants
American Indian or Alaska Native 0 1 1
Asian 3 3 6
Black 68 61 129
Native Hawaiian or Pacific Islander 2 1 3
White 200 199 399
Other 9 13 22
Not Permitted 2 3 5
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 284 participants 281 participants 565 participants
Hispanic or Latino 61 49 110
Not Hispanic or Latino 220 229 449
Not Permitted 3 3 6
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 284 participants 281 participants 565 participants
Canada 24 25 49
Austria 2 1 3
United States 216 215 431
France 12 14 26
Germany 30 26 56
HIV-1 RNA Category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 284 participants 281 participants 565 participants
< 50 copies/mL 276 275 551
≥ 50 copies/mL 8 6 14
CD4 Cell Count  
Mean (Standard Deviation)
Unit of measure:  Cells/μL
Number Analyzed 284 participants 281 participants 565 participants
714  (309.1) 658  (294.7) 686  (303.1)
CD4 Cell Count Category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 284 participants 281 participants 565 participants
< 50 Cells/ μL 0 1 1
≥ 50 to < 200 Cells/μL 6 6 12
≥ 200 to < 350 Cells/μL 18 34 52
≥ 350 to < 500 Cells/μL 53 44 97
≥ 500 Cells/ μL 207 196 403
1.Primary Outcome
Title Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US 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
The Full Analysis Set included participants who were randomized and received at least 1 dose of study drug.
Arm/Group Title B/F/TAF DTG + F/TAF
Hide Arm/Group Description:
B/F/TAF (50/200/25 mg) FDC tablet + DTG placebo tablet + F/TAF placebo tablet administered orally once daily without regard to food for 48 weeks.
DTG 50 mg tablet + F/TAF (200/25 mg) FDC tablet + B/F/TAF placebo tablet administered orally once daily without regard to food for 48 weeks.
Overall Number of Participants Analyzed 284 281
Measure Type: Number
Unit of Measure: percentage of participants
0.4 1.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection B/F/TAF, DTG + F/TAF
Comments The null hypothesis was that the B/F/TAF group is at least 4% higher than the DTG + F/TAF group with respect to the percentage of participants with HIV-1 RNA ≥ 50 copies/mL as determined by the US FDA-defined snapshot algorithm at Week 48; the alternative hypothesis was that the B/F/TAF group is less than 4% higher than the DTG + F/TAF group with respect to the percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48.
Type of Statistical Test Non-Inferiority
Comments A sample size of 260 participants per treatment group would provide at least 90% power to detect a non-inferiority margin of 4% in difference in percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 between the two treatment groups. This was based on the assumptions that both treatment groups have 2% of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 (based on Gilead Genvoya and Stribild studies) and that the significance level of the test is at a one-sided 0.025 level.
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value -0.7
Confidence Interval (2-Sided) 95.001%
-2.8 to 1.0
Estimation Comments The differences in percentages of participants between treatment groups and their 95.001% confidence intervals (CI) were calculated based on an unconditional exact method using 2 inverted 1-sided tests.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection B/F/TAF, DTG + F/TAF
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
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 Defined by the US FDA-Defined Snapshot Algorithm
Hide Description The percentage of participants achieving 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
Participants in the Full Analysis Set were analyzed.
Arm/Group Title B/F/TAF DTG + F/TAF
Hide Arm/Group Description:
B/F/TAF (50/200/25 mg) FDC tablet + DTG placebo tablet + F/TAF placebo tablet administered orally once daily without regard to food for 48 weeks.
DTG 50 mg tablet + F/TAF (200/25 mg) FDC tablet + B/F/TAF placebo tablet administered orally once daily without regard to food for 48 weeks.
Overall Number of Participants Analyzed 284 281
Measure Type: Number
Unit of Measure: percentage of participants
93.3 91.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection B/F/TAF, DTG + F/TAF
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments It would be concluded that B/F/TAF is noninferior to DTG+F/TAF if the lower bound of the 2-sided 95.001% CI of the difference between treatment groups (B/F/TAF group -DTG+F/TAF 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 2.2
Confidence Interval (2-Sided) 95.001%
-2.3 to 6.8
Estimation Comments The differences in percentages of participants between treatment groups and their 95.001% CI were calculated based on an unconditional exact method using 2 inverted 1-sided tests.
3.Secondary Outcome
Title Change From Baseline in CD4+ Cell Count at Week 48
Hide Description [Not Specified]
Time Frame Baseline; 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 DTG + F/TAF
Hide Arm/Group Description:
B/F/TAF (50/200/25 mg) FDC tablet + DTG placebo tablet + F/TAF placebo tablet administered orally once daily without regard to food for 48 weeks.
DTG 50 mg tablet + F/TAF (200/25 mg) FDC tablet + B/F/TAF placebo tablet administered orally once daily without regard to food for 48 weeks.
Overall Number of Participants Analyzed 262 256
Mean (Standard Deviation)
Unit of Measure: cells/µL
18  (179.1) 36  (152.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection B/F/TAF, DTG + F/TAF
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23
Comments [Not Specified]
Method ANOVA
Comments P-value, difference in least squares means (LSM), and its 95% CI were from ANOVA model with treatment group as a fixed effect in the model.
Method of Estimation Estimation Parameter Difference in LSM
Estimated Value -18
Confidence Interval (2-Sided) 95%
-46 to 11
Estimation Comments [Not Specified]
Time Frame First dose date up to the Week 48 Data Cut
Adverse Event Reporting Description The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
 
Arm/Group Title B/F/TAF DTG + F/TAF
Hide Arm/Group Description

Double-Blind Phase: B/F/TAF (50/200/25 mg) FDC tablet + DTG placebo tablet + F/TAF placebo tablet administered orally once daily without regard to food for 48 weeks.

Open-Label Extension Phase: After Week 48, participants will continue to take their blinded study drug and attended visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants in a country where B/F/TAF FDC is not available will be given the option to receive open-label B/F/TAF for up to 96 weeks, or until the product becomes accessible through an access program, or until Gilead elects to discontinue the study in that country, whichever occurs first.

Double-Blind Phase: DTG 50 mg tablet + F/TAF (200/25 mg) FDC tablet + B/F/TAF placebo tablet administered orally once daily without regard to food for 48 weeks.

Open-Label Extension Phase: After Week 48, participants will continue to take their blinded study drug and attended visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants in a country where B/F/TAF FDC is not available will be given the option to receive open-label B/F/TAF for up to 96 weeks, or until the product becomes accessible through an access program, or until Gilead elects to discontinue the study in that country, whichever occurs first.

All-Cause Mortality
B/F/TAF DTG + F/TAF
Affected / at Risk (%) Affected / at Risk (%)
Total   2/284 (0.70%)   1/281 (0.36%) 
Hide Serious Adverse Events
B/F/TAF DTG + F/TAF
Affected / at Risk (%) Affected / at Risk (%)
Total   30/284 (10.56%)   19/281 (6.76%) 
Cardiac disorders     
Angina pectoris  1  0/284 (0.00%)  1/281 (0.36%) 
Cardio-respiratory arrest  1  1/284 (0.35%)  0/281 (0.00%) 
Coronary artery disease  1  1/284 (0.35%)  0/281 (0.00%) 
Myocardial infarction  1  0/284 (0.00%)  1/281 (0.36%) 
Sinus tachycardia  1  1/284 (0.35%)  0/281 (0.00%) 
Ventricular tachycardia  1  1/284 (0.35%)  0/281 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  0/284 (0.00%)  1/281 (0.36%) 
Inguinal hernia  1  0/284 (0.00%)  1/281 (0.36%) 
Large intestine perforation  1  1/284 (0.35%)  0/281 (0.00%) 
Vomiting  1  0/284 (0.00%)  1/281 (0.36%) 
General disorders     
Chest pain  1  1/284 (0.35%)  0/281 (0.00%) 
Hepatobiliary disorders     
Biliary dyskinesia  1  1/284 (0.35%)  0/281 (0.00%) 
Cholecystitis  1  1/284 (0.35%)  1/281 (0.36%) 
Cholecystitis acute  1  0/284 (0.00%)  1/281 (0.36%) 
Infections and infestations     
Appendicitis  1  0/284 (0.00%)  1/281 (0.36%) 
Cellulitis  1  1/284 (0.35%)  0/281 (0.00%) 
Device related infection  1  1/284 (0.35%)  0/281 (0.00%) 
Diarrhoea infectious  1  1/284 (0.35%)  0/281 (0.00%) 
Diverticulitis  1  2/284 (0.70%)  1/281 (0.36%) 
Gastroenteritis  1  1/284 (0.35%)  0/281 (0.00%) 
Perirectal abscess  1  1/284 (0.35%)  0/281 (0.00%) 
Pneumonia  1  1/284 (0.35%)  0/281 (0.00%) 
Post procedural infection  1  1/284 (0.35%)  0/281 (0.00%) 
Pyelonephritis  1  1/284 (0.35%)  1/281 (0.36%) 
Viral upper respiratory tract infection  1  0/284 (0.00%)  1/281 (0.36%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  0/284 (0.00%)  1/281 (0.36%) 
Clavicle fracture  1  1/284 (0.35%)  0/281 (0.00%) 
Concussion  1  1/284 (0.35%)  0/281 (0.00%) 
Foreign body in gastrointestinal tract  1  1/284 (0.35%)  0/281 (0.00%) 
Ligament rupture  1  1/284 (0.35%)  0/281 (0.00%) 
Lisfranc fracture  1  0/284 (0.00%)  1/281 (0.36%) 
Overdose  1  1/284 (0.35%)  0/281 (0.00%) 
Subdural haemorrhage  1  0/284 (0.00%)  1/281 (0.36%) 
Tendon rupture  1  1/284 (0.35%)  0/281 (0.00%) 
Investigations     
Blood glucose increased  1  0/284 (0.00%)  1/281 (0.36%) 
Musculoskeletal and connective tissue disorders     
Lumbar spinal stenosis  1  1/284 (0.35%)  0/281 (0.00%) 
Osteonecrosis  1  0/284 (0.00%)  1/281 (0.36%) 
Rhabdomyolysis  1  1/284 (0.35%)  0/281 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung neoplasm malignant  1  1/284 (0.35%)  0/281 (0.00%) 
Yolk sac tumour site unspecified  1  0/284 (0.00%)  1/281 (0.36%) 
Nervous system disorders     
Seizure  1  1/284 (0.35%)  0/281 (0.00%) 
Vertebral artery dissection  1  0/284 (0.00%)  1/281 (0.36%) 
Psychiatric disorders     
Drug abuse  1  1/284 (0.35%)  0/281 (0.00%) 
Rebound psychosis  1  1/284 (0.35%)  0/281 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Bronchospasm  1  1/284 (0.35%)  0/281 (0.00%) 
Chronic obstructive pulmonary disease  1  1/284 (0.35%)  0/281 (0.00%) 
Dyspnoea  1  1/284 (0.35%)  1/281 (0.36%) 
Pneumonitis  1  1/284 (0.35%)  0/281 (0.00%) 
Pneumothorax  1  1/284 (0.35%)  0/281 (0.00%) 
1
Term from vocabulary, MedDRA 21.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
B/F/TAF DTG + F/TAF
Affected / at Risk (%) Affected / at Risk (%)
Total   129/284 (45.42%)   133/281 (47.33%) 
Gastrointestinal disorders     
Diarrhoea  1  23/284 (8.10%)  32/281 (11.39%) 
General disorders     
Fatigue  1  21/284 (7.39%)  8/281 (2.85%) 
Infections and infestations     
Influenza  1  16/284 (5.63%)  14/281 (4.98%) 
Nasopharyngitis  1  32/284 (11.27%)  28/281 (9.96%) 
Upper respiratory tract infection  1  20/284 (7.04%)  30/281 (10.68%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  16/284 (5.63%)  17/281 (6.05%) 
Back pain  1  15/284 (5.28%)  11/281 (3.91%) 
Nervous system disorders     
Headache  1  13/284 (4.58%)  23/281 (8.19%) 
Psychiatric disorders     
Insomnia  1  18/284 (6.34%)  11/281 (3.91%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  6/284 (2.11%)  16/281 (5.69%) 
1
Term from vocabulary, MedDRA 21.1
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
Layout table for Results Point of Contact information
Name/Title: Gilead Clinical Study Information Center
Organization: Gilead Sciences
Phone: 1-833-445-3230 (GILEAD-0)
EMail: GileadClinicalTrials@gilead.com
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT03110380    
Other Study ID Numbers: GS-US-380-4030
2017-000308-17 ( EudraCT Number )
First Submitted: April 7, 2017
First Posted: April 12, 2017
Results First Submitted: November 1, 2019
Results First Posted: November 20, 2019
Last Update Posted: December 22, 2020