Switching to a Fixed Dose Combination of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) in Human Immunodeficiency Virus Type 1 (HIV-1) Infected Adults Who Are Virologically Suppressed
Study Details
Study Description
Brief Summary
The primary objective of this study is to evaluate the efficacy of switching from a regimen of either dolutegravir (DTG) and emtricitabine /tenofovir alafenamide (F/TAF) or DTG and emtricitabine/tenofovir disoproxil fumarate (F/TDF) to a fixed dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus DTG+F/TAF in virologically suppressed HIV-1 infected adults with or without antiretroviral (ARV) resistance.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: B/F/TAF Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) fixed-dose combination (FDC) tablet + dolutegravir (DTG) placebo tablet + emtricitabine/tenofovir alafenamide (F/TAF) placebo tablet administered without regard to food for at least 48 weeks. |
Drug: B/F/TAF
50/200/25 mg FDC tablet(s) administered orally once daily
Other Names:
Drug: DTG Placebo
Tablet(s) administered orally once daily
Drug: F/TAF Placebo
Tablet(s) administered orally once daily
|
Active Comparator: DTG + F/TAF DTG 50 mg tablet + F/TAF FDC tablet + B/F/TAF placebo tablet administered without regard to food for at least 48 weeks. |
Drug: F/TAF
200/25 mg FDC tablet(s) administered orally once daily
Other Names:
Drug: DTG
50 mg tablet(s) administered orally once daily
Other Names:
Drug: B/F/TAF Placebo
Tablet(s) administered orally once daily
|
Experimental: Open-label Phase B/F/TAF from B/F/TAF Participants who received B/F/TAF in double-blind phase and from a country where B/F/TAF was not available were given the option to receive B/F/TAF orally once daily for up to 96 weeks in the open-label extension phase. |
Drug: B/F/TAF
50/200/25 mg FDC tablet(s) administered orally once daily
Other Names:
|
Experimental: Open-label Phase B/F/TAF from DTG + F/TAF Participants who received DTG + F/TAF in double-blind phase and from a country where B/F/TAF was not available were given the option to receive B/F/TAF orally once daily for up to 96 weeks in the open-label extension phase. |
Drug: B/F/TAF
50/200/25 mg FDC tablet(s) administered orally once daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm [Week 48]
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.
Secondary Outcome Measures
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm [Week 48]
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.
- Change From Baseline in CD4+ Cell Count at Week 48 [Baseline; Week 48]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Currently receiving an ARV regimen of DTG+F/TAF or DTG+F/TDF for the following minimum time periods:
-
≥ 6 months (if there is documented or suspected nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance prior to the screening visit)
-
≥ 3 months (if there is no documented or suspected NRTI resistance prior to the screening visit)
-
Documented plasma HIV-1 ribonucleic acid (RNA) < 50 copies/mL during treatment with DTG+F/TAF or DTG+F/TDF (for a minimum period of ≥ 6 or ≥ 3 months, as applicable) preceding the screening visit
-
Plasma HIV-1 RNA levels < 50 copies/mL at screening visit
-
Estimated Glomerular Filtration Rate (eGFR) ≥ 30 mL/min according to the Cockcroft-Gault formula for creatinine clearance
-
No documented resistance to integrase stand transfer inhibitors (INSTIs) or confirmed virologic failure
-
Eligible adults with chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection are permitted to enroll
NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Spectrum Medical Group | Phoenix | Arizona | United States | 85012 |
2 | Ruane Clinical Research Group Inc. | Los Angeles | California | United States | 90036 |
3 | Mills Clinical Research | Los Angeles | California | United States | 90069 |
4 | Highland Hospital - Alameda Health System | Oakland | California | United States | 94602 |
5 | Cares Community Health | Sacramento | California | United States | 95814 |
6 | Kaiser Permanente | Sacramento | California | United States | 95825 |
7 | Hepatitis/HIV Clinical Trials Group (HHCTG) | San Francisco | California | United States | 94110 |
8 | Kaiser Permanente | San Francisco | California | United States | 94118 |
9 | Kaiser Permanente, Department of Infectious Diseases | San Leandro | California | United States | 94577 |
10 | University of Colorado Denver, University of Colorado Hospital | Aurora | Colorado | United States | 80045 |
11 | Whitman-Walker Institute | Washington | District of Columbia | United States | 20005 |
12 | Dupont Circle Physician's Group | Washington | District of Columbia | United States | 20009 |
13 | Providence Hospital Center for Infectious Diseases | Washington | District of Columbia | United States | 20017 |
14 | The GW Medical Faculty Associates | Washington | District of Columbia | United States | 20037 |
15 | Midland Florida Clinical Research Center, LLC | DeLand | Florida | United States | 32720 |
16 | Therafirst Medical Center | Fort Lauderdale | Florida | United States | 33308 |
17 | Gary J. Richmond, M.D., P.A. | Fort Lauderdale | Florida | United States | 33316 |
18 | Midway Immunology and Research Center | Fort Pierce | Florida | United States | 34982 |
19 | AIDS Healthcare Foundation - South Beach | Miami Beach | Florida | United States | 33140 |
20 | University of Miami Divison of Infectious Diseases Clinical Research Unit | Miami | Florida | United States | 33136 |
21 | Orlando Immunology Center | Orlando | Florida | United States | 32803 |
22 | AHF-Pensacola | Pensacola | Florida | United States | 32503 |
23 | Infectious Disease Research Institute Inc | Tampa | Florida | United States | 33614 |
24 | St. Joseph's Hospital Comprehensive Research Institute | Tampa | Florida | United States | 33614 |
25 | AIDS Research and Treatment Center of the Treasure Coast | Vero Beach | Florida | United States | 32960 |
26 | Triple O Research Institute, P.A. | West Palm Beach | Florida | United States | 33407 |
27 | Emory Hospital Midtown Infectious Disease Clinic | Atlanta | Georgia | United States | 30308 |
28 | AIDS Research Consortium of Atlanta | Atlanta | Georgia | United States | 30312 |
29 | AU Medical Center | Augusta | Georgia | United States | 30912 |
30 | Infectious Disease Specialists of Atlanta | Decatur | Georgia | United States | 30033 |
31 | Mercer University, Department of Internal Medicine | Macon | Georgia | United States | 31201 |
32 | Chatham County Health Department | Savannah | Georgia | United States | 31401 |
33 | John A. Burns School of Medicine, University of Hawaii Clinics at Kaka'ako | Honolulu | Hawaii | United States | 96813 |
34 | University of Louisville 550 Clinic | Louisville | Kentucky | United States | 40202 |
35 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02115 |
36 | Boston Medical Center | Boston | Massachusetts | United States | 02118 |
37 | Community Research Initiative of New England | Boston | Massachusetts | United States | 02129 |
38 | Metro West Medical Center | Framingham | Massachusetts | United States | 01702 |
39 | Claudia T Martorell, MD., LLC d/b/a The Research Institute | Springfield | Massachusetts | United States | 01105 |
40 | Be Well Medical Center | Berkley | Michigan | United States | 48072 |
41 | Abbott Northwestern Hospital part of Allina Health | Minneapolis | Minnesota | United States | 55407 |
42 | Hennepin County Medical Center, Positive Care Clinic | Minneapolis | Minnesota | United States | 55415 |
43 | Kansas City CARE Clinic | Kansas City | Missouri | United States | 64111 |
44 | Southampton Healthcare, Inc. | Saint Louis | Missouri | United States | 63139 |
45 | Prime Healthcare Services - St. Michael's LLC d/b/a Saint Michael's Medical Center | Newark | New Jersey | United States | 07102 |
46 | Southwest CARE Center | Albuquerque | New Mexico | United States | 87109 |
47 | Southwest CARE Center | Santa Fe | New Mexico | United States | 87505 |
48 | Jacobi Medical Center | Bronx | New York | United States | 10461 |
49 | Montefiore Medical Center | Bronx | New York | United States | 10467 |
50 | North Shore University Hospital/Division of Infectious Diseases | Manhasset | New York | United States | 11030 |
51 | NC TraCS Institute - CTRC; University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27514 |
52 | Duke University Heath System | Durham | North Carolina | United States | 27710 |
53 | East Carolina University (ECU), The Brody School of Medicine, Adult Specialty Care | Greenville | North Carolina | United States | 27834 |
54 | Rosedale Infectious Diseases | Huntersville | North Carolina | United States | 28078 |
55 | Wake Forest Baptist Health | Winston-Salem | North Carolina | United States | 27157 |
56 | Medical University of South Carolina (MUSC) | Charleston | South Carolina | United States | 29425 |
57 | Palmetto Health Richland (Regulatory and Study Supply Shipping) | Columbia | South Carolina | United States | 29203 |
58 | Central Texas Clinical Research | Austin | Texas | United States | 78705 |
59 | AIDS Arms Inc/ Trinity Health and Wellness Center | Dallas | Texas | United States | 75208 |
60 | North Texas Infectious Diseases Consultants, P.A. | Dallas | Texas | United States | 75246 |
61 | Therapeutic Concepts, PA | Houston | Texas | United States | 77004 |
62 | Research Access Network | Houston | Texas | United States | 77098 |
63 | The Crofoot Research Center, INC (DBA: Gordon E. Crofoot MD PA) | Houston | Texas | United States | 77098 |
64 | DCOL Center for Clinical Research | Longview | Texas | United States | 75605 |
65 | Peter Shalit, M.D. | Seattle | Washington | United States | 98104 |
66 | MultiCare Rockwood HIV Critical Care Clinic | Spokane | Washington | United States | 99204 |
67 | Medizinische Universitat Wien, Universitatsklinik fur Dermatologie | Wien | Austria | 1090 | |
68 | Kaye Edmonton Clinic | Edmonton | Alberta | Canada | T6G 2G3 |
69 | Spectrum Health Clinic | Vancouver | British Columbia | Canada | 6Z 2T1 |
70 | Winnipeg Regional Health Authority - Health Sciences Centre Winnipeg | Winnipeg | Manitoba | Canada | R3A 1R9 |
71 | Maple Leaf Research / Maple Leaf Medical Clinic | Toronto | Ontario | Canada | M5G 1K2 |
72 | Clinique de Médecine Urbaine du Quartier Latin | Montréal | Quebec | Canada | H2L 5B1 |
73 | Chronical Viral Illness Service/McGill University Health Care (MUHC) | Montréal | Quebec | Canada | H4A 3J1 |
74 | Hôpital Saint-André | Bordeaux | France | 33075 | |
75 | Hôpital Croix-Rousse | Lyon | France | 69004 | |
76 | Hôpital Gui de Chauliac, CHU de Montpellier | Montpellier | France | 34295 | |
77 | CHU de Nice-l'Archet | Nice | France | 06202 | |
78 | CHU Bichat | Paris | France | 75018 | |
79 | AP-HP Hôpital Tenon | Paris | France | 75020 | |
80 | Hôpital Saint-Louis | Paris | France | 75475 | |
81 | Hôpital Saint-Antoine | Paris | France | 75571 | |
82 | zibp Zentrum für Infektiologie Berlin Prenzlauer Berg | Berlin | Germany | 10439 | |
83 | EPIMED Gesellschaft fur epidemiologische und klinische Forschung in der Medizin mbH | Berlin | Germany | 12157 | |
84 | Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I, Klinisches Studienzentrum Immunologie | Bonn | Germany | 53127 | |
85 | Universitätsklinikum Köln - Klinik I fur Innere Medizin - Klinisches Studienzentrum fur Infektiologie I | Cologne | Germany | 50937 | |
86 | Universitätsklinikum Essen - Klinik fur Dermatologie und Venerologie - HPSTD Ambulanz | Essen | Germany | 45122 | |
87 | Universitätsklinikum Frankfurt, Medizinische Klinik II, Schwerpunkt Infektiologie, Haus 68 | Frankfurt am Main | Germany | 60590 | |
88 | Infektiologikum Frankfurt | Frankfurt am Main | Germany | 60596 | |
89 | ICH Study Center GmbH & Co. KG | Hamburg | Germany | 20146 | |
90 | Universitätsklinikum Hamburg- Eppendorf - Ambulanzzentrum des Universitatsklinikums Eppendorf GmbH - Bereich Infektiologie | Hamburg | Germany | 20246 | |
91 | Instituto de Investigacion Cientifica del Sur | Ponce | Puerto Rico | 00730 | |
92 | Hope Clinical Research | San Juan | Puerto Rico | 00909 | |
93 | Proyecto ACTU | San Juan | Puerto Rico | 00935 | |
94 | Clinical Research Puerto Rico | San Juan | Puerto Rico | 909 |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
More Information
Publications
None provided.- GS-US-380-4030
- 2017-000308-17
Study Results
Participant Flow
Recruitment Details | Participants were enrolled at study sites in North America and Europe. The first participant was screened on 12 June 2017. The last study visit occurred on 10 Feb 2021. |
---|---|
Pre-assignment Detail | 633 participants were screened. |
Arm/Group Title | B/F/TAF | DTG + F/TAF | B/F/TAF From B/F/TAF | B/F/TAF From DTG + F/TAF |
---|---|---|---|---|
Arm/Group Description | 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 at least 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 at least 48 weeks. | Participants who received B/F/TAF in double-blind phase and from a country where B/F/TAF was not available were given the option to receive B/F/TAF orally once daily for up to 96 weeks in the open-label extension phase. | Participants who received DTG + F/TAF in double-blind phase and from a country where B/F/TAF was not available were given the option to receive B/F/TAF orally once daily for up to 96 weeks in the open-label extension phase. |
Period Title: Double-Blind Treatment Phase | ||||
STARTED | 284 | 283 | 0 | 0 |
Safety Analysis Set | 284 | 281 | 0 | 0 |
COMPLETED | 263 | 253 | 0 | 0 |
NOT COMPLETED | 21 | 30 | 0 | 0 |
Period Title: Double-Blind Treatment Phase | ||||
STARTED | 0 | 0 | 125 | 116 |
COMPLETED | 0 | 0 | 121 | 113 |
NOT COMPLETED | 0 | 0 | 4 | 3 |
Baseline Characteristics
Arm/Group Title | B/F/TAF | DTG + F/TAF | Total |
---|---|---|---|
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 at least 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 at least 48 weeks. | Total of all reporting groups |
Overall Participants | 284 | 281 | 565 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
50
(11.3)
|
49
(11.3)
|
50
(11.3)
|
Sex: Female, Male (Count of Participants) | |||
Female |
39
13.7%
|
41
14.6%
|
80
14.2%
|
Male |
245
86.3%
|
240
85.4%
|
485
85.8%
|
Race/Ethnicity, Customized (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
1
0.4%
|
1
0.2%
|
Asian |
3
1.1%
|
3
1.1%
|
6
1.1%
|
Black |
68
23.9%
|
61
21.7%
|
129
22.8%
|
Native Hawaiian or Pacific Islander |
2
0.7%
|
1
0.4%
|
3
0.5%
|
White |
200
70.4%
|
199
70.8%
|
399
70.6%
|
Other |
9
3.2%
|
13
4.6%
|
22
3.9%
|
Not Permitted |
2
0.7%
|
3
1.1%
|
5
0.9%
|
Race/Ethnicity, Customized (Count of Participants) | |||
Hispanic or Latino |
61
21.5%
|
49
17.4%
|
110
19.5%
|
Not Hispanic or Latino |
220
77.5%
|
229
81.5%
|
449
79.5%
|
Not Permitted |
3
1.1%
|
3
1.1%
|
6
1.1%
|
Region of Enrollment (Count of Participants) | |||
Canada |
24
8.5%
|
25
8.9%
|
49
8.7%
|
Austria |
2
0.7%
|
1
0.4%
|
3
0.5%
|
United States |
197
69.4%
|
202
71.9%
|
399
70.6%
|
France |
12
4.2%
|
14
5%
|
26
4.6%
|
Germany |
30
10.6%
|
26
9.3%
|
56
9.9%
|
Puerto Rico |
19
6.7%
|
13
4.6%
|
32
5.7%
|
HIV-1 RNA Category (Count of Participants) | |||
< 50 copies/mL |
276
97.2%
|
275
97.9%
|
551
97.5%
|
≥ 50 copies/mL |
8
2.8%
|
6
2.1%
|
14
2.5%
|
CD4 Cell Count (Cells/μL) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [Cells/μL] |
714
(309.1)
|
658
(294.7)
|
686
(303.1)
|
CD4 Cell Count Category (Count of Participants) | |||
< 50 Cells/ μL |
0
0%
|
1
0.4%
|
1
0.2%
|
≥ 50 to < 200 Cells/μL |
6
2.1%
|
6
2.1%
|
12
2.1%
|
≥ 200 to < 350 Cells/μL |
18
6.3%
|
34
12.1%
|
52
9.2%
|
≥ 350 to < 500 Cells/μL |
53
18.7%
|
44
15.7%
|
97
17.2%
|
≥ 500 Cells/ μL |
207
72.9%
|
196
69.8%
|
403
71.3%
|
Outcome Measures
Title | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm |
---|---|
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 |
Outcome Measure Data
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 |
---|---|---|
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 at least 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 at least 48 weeks. |
Measure Participants | 284 | 281 |
Number [percentage of participants] |
0.4
0.1%
|
1.1
0.4%
|
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. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Difference in Percentages |
Estimated Value | -0.7 | |
Confidence Interval |
(2-Sided) 95.001% -2.8 to 1.0 |
|
Parameter Dispersion |
Type: Value: |
|
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. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | B/F/TAF, DTG + F/TAF |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.37 |
Comments | ||
Method | Fisher Exact | |
Comments |
Title | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm |
---|---|
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 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in the Full Analysis Set were analyzed. |
Arm/Group Title | B/F/TAF | DTG + F/TAF |
---|---|---|
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 at least 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 at least 48 weeks. |
Measure Participants | 284 | 281 |
Number [percentage of participants] |
93.3
32.9%
|
91.1
32.4%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | B/F/TAF, DTG + F/TAF |
---|---|---|
Comments | ||
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%. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Difference in Percentages |
Estimated Value | 2.2 | |
Confidence Interval |
(2-Sided) 95.001% -2.3 to 6.8 |
|
Parameter Dispersion |
Type: Value: |
|
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. |
Title | Change From Baseline in CD4+ Cell Count at Week 48 |
---|---|
Description | |
Time Frame | Baseline; Week 48 |
Outcome Measure Data
Analysis Population Description |
---|
Participants in the Full Analysis Set with available data were analyzed. |
Arm/Group Title | B/F/TAF | DTG + F/TAF |
---|---|---|
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 at least 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 at least 48 weeks. |
Measure Participants | 262 | 256 |
Mean (Standard Deviation) [cells/µL] |
18
(179.1)
|
36
(152.6)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | B/F/TAF, DTG + F/TAF |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.23 |
Comments | ||
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 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | Adverse Events: First dose date up to last dose date [maximum: 84.9 weeks (Blinded Phase), 179.6 weeks (Open Label Phase) plus 30 days All-Cause Mortality: Randomization/Enrollment up to 187.7 weeks | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | Adverse Events: The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug. All-Cause Mortality: The All Randomized Analysis Set included all participants who were randomized into the study. | |||||||
Arm/Group Title | Double-Blind Treatment Phase B/F/TAF | Double-Blind Treatment Phase DTG + F/TAF | Open-label Extension Phase B/F/TAF From B/F/TAF | Open-label Extension Phase B/F/TAF From DTG + F/TAF | ||||
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 atleast 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 atleast 48 weeks. | Participants who received B/F/TAF in double-blind phase and from a country where B/F/TAF was not available were given the option to receive B/F/TAF orally once daily for up to 96 weeks in the open-label extension phase. | Participants who received DTG + F/TAF in double-blind phase and from a country where B/F/TAF was not available were given the option to receive B/F/TAF orally once daily for up to 96 weeks in the open-label extension phase. | ||||
All Cause Mortality |
||||||||
Double-Blind Treatment Phase B/F/TAF | Double-Blind Treatment Phase DTG + F/TAF | Open-label Extension Phase B/F/TAF From B/F/TAF | Open-label Extension Phase B/F/TAF From DTG + F/TAF | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/284 (1.1%) | 2/283 (0.7%) | 0/125 (0%) | 0/117 (0%) | ||||
Serious Adverse Events |
||||||||
Double-Blind Treatment Phase B/F/TAF | Double-Blind Treatment Phase DTG + F/TAF | Open-label Extension Phase B/F/TAF From B/F/TAF | Open-label Extension Phase B/F/TAF From DTG + F/TAF | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 36/284 (12.7%) | 27/281 (9.6%) | 12/125 (9.6%) | 11/116 (9.5%) | ||||
Blood and lymphatic system disorders | ||||||||
Lymphocytic infiltration | 0/284 (0%) | 0/281 (0%) | 0/125 (0%) | 1/116 (0.9%) | ||||
Cardiac disorders | ||||||||
Acute myocardial infarction | 0/284 (0%) | 0/281 (0%) | 2/125 (1.6%) | 0/116 (0%) | ||||
Angina pectoris | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Cardiac failure congestive | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Cardio-respiratory arrest | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Coronary artery disease | 2/284 (0.7%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Myocardial infarction | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Sinus tachycardia | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Ventricular tachycardia | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Gastrointestinal disorders | ||||||||
Abdominal pain | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 1/116 (0.9%) | ||||
Colitis | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Inguinal hernia | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Large intestine perforation | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Obstructive pancreatitis | 0/284 (0%) | 0/281 (0%) | 1/125 (0.8%) | 0/116 (0%) | ||||
Vomiting | 0/284 (0%) | 1/281 (0.4%) | 1/125 (0.8%) | 0/116 (0%) | ||||
General disorders | ||||||||
Chest pain | 1/284 (0.4%) | 0/281 (0%) | 1/125 (0.8%) | 1/116 (0.9%) | ||||
Death | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Non-cardiac chest pain | 0/284 (0%) | 0/281 (0%) | 0/125 (0%) | 1/116 (0.9%) | ||||
Hepatobiliary disorders | ||||||||
Biliary dyskinesia | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Cholangitis acute | 0/284 (0%) | 0/281 (0%) | 0/125 (0%) | 1/116 (0.9%) | ||||
Cholecystitis | 1/284 (0.4%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Cholecystitis acute | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Immune system disorders | ||||||||
Anti-neutrophil cytoplasmic antibody positive vasculitis | 0/284 (0%) | 0/281 (0%) | 0/125 (0%) | 1/116 (0.9%) | ||||
Infections and infestations | ||||||||
Appendicitis | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Bronchitis | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Cellulitis | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Cellulitis orbital | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Colonic abscess | 0/284 (0%) | 0/281 (0%) | 0/125 (0%) | 1/116 (0.9%) | ||||
Covid-19 pneumonia | 0/284 (0%) | 0/281 (0%) | 1/125 (0.8%) | 0/116 (0%) | ||||
Device related infection | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Diarrhoea infectious | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Diverticulitis | 2/284 (0.7%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Epididymitis | 0/284 (0%) | 0/281 (0%) | 0/125 (0%) | 1/116 (0.9%) | ||||
Gastroenteritis | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Meningitis | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Perirectal abscess | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Pneumonia | 1/284 (0.4%) | 2/281 (0.7%) | 0/125 (0%) | 2/116 (1.7%) | ||||
Post procedural infection | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Pyelonephritis | 1/284 (0.4%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Sepsis | 0/284 (0%) | 0/281 (0%) | 0/125 (0%) | 1/116 (0.9%) | ||||
Viral upper respiratory tract infection | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Wound infection | 0/284 (0%) | 0/281 (0%) | 1/125 (0.8%) | 0/116 (0%) | ||||
Injury, poisoning and procedural complications | ||||||||
Ankle fracture | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Clavicle fracture | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Concussion | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Facial bones fracture | 0/284 (0%) | 0/281 (0%) | 1/125 (0.8%) | 0/116 (0%) | ||||
Foreign body in gastrointestinal tract | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Hip fracture | 0/284 (0%) | 0/281 (0%) | 0/125 (0%) | 1/116 (0.9%) | ||||
Ligament rupture | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Lisfranc fracture | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Overdose | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Rib fracture | 0/284 (0%) | 0/281 (0%) | 1/125 (0.8%) | 0/116 (0%) | ||||
Subdural haematoma | 0/284 (0%) | 0/281 (0%) | 1/125 (0.8%) | 0/116 (0%) | ||||
Subdural haemorrhage | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Tendon rupture | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Investigations | ||||||||
Blood glucose increased | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Lipase increased | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Liver function test increased | 0/284 (0%) | 0/281 (0%) | 0/125 (0%) | 1/116 (0.9%) | ||||
Transaminases increased | 0/284 (0%) | 0/281 (0%) | 1/125 (0.8%) | 0/116 (0%) | ||||
Metabolism and nutrition disorders | ||||||||
Dehydration | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Hyperglycaemia | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Hypokalaemia | 0/284 (0%) | 0/281 (0%) | 1/125 (0.8%) | 0/116 (0%) | ||||
Musculoskeletal and connective tissue disorders | ||||||||
Lumbar spinal stenosis | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Myalgia | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Osteonecrosis | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Osteoporosis | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Rhabdomyolysis | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Spondylolisthesis | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
Lung neoplasm malignant | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Metastases to spine | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Yolk sac tumour site unspecified | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Nervous system disorders | ||||||||
Cerebrovascular accident | 0/284 (0%) | 0/281 (0%) | 1/125 (0.8%) | 1/116 (0.9%) | ||||
Sciatica | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Seizure | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Vertebral artery dissection | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Psychiatric disorders | ||||||||
Alcohol withdrawal syndrome | 0/284 (0%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Drug abuse | 2/284 (0.7%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Psychotic disorder | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Rebound psychosis | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Renal and urinary disorders | ||||||||
Acute kidney injury | 0/284 (0%) | 0/281 (0%) | 0/125 (0%) | 1/116 (0.9%) | ||||
Nephrolithiasis | 0/284 (0%) | 0/281 (0%) | 1/125 (0.8%) | 0/116 (0%) | ||||
Urinary tract obstruction | 0/284 (0%) | 0/281 (0%) | 1/125 (0.8%) | 0/116 (0%) | ||||
Respiratory, thoracic and mediastinal disorders | ||||||||
Bronchospasm | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Chronic obstructive pulmonary disease | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Dyspnoea | 2/284 (0.7%) | 1/281 (0.4%) | 0/125 (0%) | 0/116 (0%) | ||||
Pneumonia aspiration | 0/284 (0%) | 0/281 (0%) | 0/125 (0%) | 1/116 (0.9%) | ||||
Pneumonitis | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Pneumothorax | 1/284 (0.4%) | 0/281 (0%) | 0/125 (0%) | 0/116 (0%) | ||||
Skin and subcutaneous tissue disorders | ||||||||
Purpura | 0/284 (0%) | 0/281 (0%) | 0/125 (0%) | 1/116 (0.9%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
Double-Blind Treatment Phase B/F/TAF | Double-Blind Treatment Phase DTG + F/TAF | Open-label Extension Phase B/F/TAF From B/F/TAF | Open-label Extension Phase B/F/TAF From DTG + F/TAF | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 181/284 (63.7%) | 170/281 (60.5%) | 30/125 (24%) | 33/116 (28.4%) | ||||
Gastrointestinal disorders | ||||||||
Diarrhoea | 26/284 (9.2%) | 35/281 (12.5%) | 4/125 (3.2%) | 7/116 (6%) | ||||
General disorders | ||||||||
Fatigue | 22/284 (7.7%) | 9/281 (3.2%) | 1/125 (0.8%) | 7/116 (6%) | ||||
Infections and infestations | ||||||||
Bronchitis | 18/284 (6.3%) | 14/281 (5%) | 4/125 (3.2%) | 5/116 (4.3%) | ||||
Influenza | 19/284 (6.7%) | 17/281 (6%) | 2/125 (1.6%) | 1/116 (0.9%) | ||||
Nasopharyngitis | 44/284 (15.5%) | 32/281 (11.4%) | 3/125 (2.4%) | 1/116 (0.9%) | ||||
Sinusitis | 16/284 (5.6%) | 11/281 (3.9%) | 1/125 (0.8%) | 4/116 (3.4%) | ||||
Upper respiratory tract infection | 33/284 (11.6%) | 40/281 (14.2%) | 9/125 (7.2%) | 10/116 (8.6%) | ||||
Musculoskeletal and connective tissue disorders | ||||||||
Arthralgia | 24/284 (8.5%) | 21/281 (7.5%) | 4/125 (3.2%) | 4/116 (3.4%) | ||||
Back pain | 20/284 (7%) | 15/281 (5.3%) | 2/125 (1.6%) | 3/116 (2.6%) | ||||
Pain in extremity | 15/284 (5.3%) | 15/281 (5.3%) | 1/125 (0.8%) | 4/116 (3.4%) | ||||
Nervous system disorders | ||||||||
Headache | 16/284 (5.6%) | 23/281 (8.2%) | 1/125 (0.8%) | 4/116 (3.4%) | ||||
Psychiatric disorders | ||||||||
Insomnia | 19/284 (6.7%) | 14/281 (5%) | 1/125 (0.8%) | 3/116 (2.6%) | ||||
Respiratory, thoracic and mediastinal disorders | ||||||||
Cough | 11/284 (3.9%) | 16/281 (5.7%) | 4/125 (3.2%) | 2/116 (1.7%) | ||||
Skin and subcutaneous tissue disorders | ||||||||
Rash | 9/284 (3.2%) | 15/281 (5.3%) | 0/125 (0%) | 2/116 (1.7%) | ||||
Vascular disorders | ||||||||
Hypertension | 15/284 (5.3%) | 11/281 (3.9%) | 3/125 (2.4%) | 0/116 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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) |
GileadClinicalTrials@gilead.com |
- GS-US-380-4030
- 2017-000308-17