HIV-1 Infection
Conditions
Keywords
HIV
Brief summary
The primary objective of this study is to evaluate the noninferiority of switching to emtricitabine/rilpivirine /tenofovir alafenamide (FTC/RPV/TAF) fixed-dose combination (FDC) as compared to continuing FTC/RPV/tenofovir disoproxil fumarate (TDF) FDC (FTC/RPV/TDF) in virologically suppressed HIV-1 infected participants.
Interventions
DRUGFTC/RPV/TAF
200/25/25 mg FDC tablets administered orally once daily
DRUGFTC/RPV/TDF Placebo
Tablets administered orally once daily
DRUGFTC/RPV/TDF
200/25/300 mg FDC tablets administered orally once daily
Tablets administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures * Currently receiving FTC/RPV/TDF FDC for ≥ 6 consecutive months preceding the screening visit * Documented plasma HIV-1 RNA levels \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is \> 50 copies/mL) for ≥ 6 months preceding the screening visit. After reaching HIV-1 RNA \< 50 copies/mL, single values of HIV-1 RNA ≥ 50 copies/mL followed by resuppression, are allowed * Have no documented resistance to any of the study agents at any time in the past * HIV-1 RNA \< 50 copies/mL at the screening visit * Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN) * Total bilirubin ≤ 1.5 mg/dL (≤ 26 μmol/L), or normal direct bilirubin * Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm\^3 (1.00 GI/L); platelets ≥ 50,000/mm\^3 (50 GI/L); hemoglobin ≥ 8.5 g/dL (85 g/L)) * Serum amylase ≤ 5 × ULN (individuals with serum amylase \> 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN) * Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant) * Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min (1.17 mL/sec) according to the Cockcroft-Gault formula Key
Exclusion criteria
* Hepatitis B surface antigen (HBsAg) positive * Hepatitis C antibody positive with detectable hepatitis C virus (HCV) RNA (individuals who have HCV antibody but no detectable HCV RNA are eligible to enroll) * Individuals experiencing or with a medical history of decompensated cirrhosis (e.g., ascites, encephalopathy, etc.) * Females who are breastfeeding * Positive serum pregnancy test * Current alcohol or substance use judged by the Investigator to potentially interfere with individual's study compliance * A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline/Day 1 and must not be anticipated to require systemic therapy during the study * Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline/Day 1 * Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements * Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial * Individuals receiving ongoing therapy with any of the disallowed medications listed in the protocol, including drugs not to be used with FTC, RPV and/or TAF; or individuals with any known allergies to the excipients of FTC/RPV/TAF Note: Other Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 US FDA-defined snapshot algorithm, which defines a patient'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
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Spine BMD at Week 48 | Baseline; Week 48 | Spine BMD was assessed by DXA scan. |
| Percent Change From Baseline in Spine BMD at Week 96 | Baseline; Week 96 | Spine BMD was assessed by DXA scan. |
| 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 patient'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. |
| Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm | Week 96 | The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a patient'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. |
| Percent Change From Baseline in Hip BMD at Week 96 | Baseline; Week 96 | Hip BMD was assessed by DXA scan. |
| Change From Baseline in CD4+ Cell Count at Week 48 | Baseline; Week 48 | — |
| Change From Baseline in CD4+ Cell Count at Week 96 | Baseline; Week 96 | — |
| Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 | Baseline; Week 48 | Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan. |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm | Week 96 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a patient'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. |
Countries
Belgium, Canada, France, Germany, Italy, Netherlands, Puerto Rico, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Europe and North America. The first participant was screened on 26 January 2015. The last study visit occurred on 09 January 2019.
Pre-assignment details
690 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| FTC/RPV/TAF FTC/RPV/TAF (200/25/25 mg) FDC tablet + FTC/RPV/TDF placebo tablet orally once daily for up to 96 weeks. | 316 |
| FTC/RPV/TDF FTC/RPV/TDF (200/25/300 mg) FDC tablet + FTC/RPV/TAF placebo tablet orally once daily for up to 96 weeks. | 314 |
| Total | 630 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Phase | Adverse Event | 2 | 3 |
| Double-Blind Phase | Death | 1 | 2 |
| Double-Blind Phase | Investigator's Discretion | 4 | 6 |
| Double-Blind Phase | Lack of Efficacy | 1 | 0 |
| Double-Blind Phase | Lost to Follow-up | 8 | 10 |
| Double-Blind Phase | Non-Compliance with Study Drug | 1 | 2 |
| Double-Blind Phase | Protocol Violation | 2 | 1 |
| Double-Blind Phase | Randomized but Never Treated | 0 | 2 |
| Double-Blind Phase | Withdrew Consent | 21 | 23 |
Baseline characteristics
| Characteristic | FTC/RPV/TAF | Total | FTC/RPV/TDF |
|---|---|---|---|
| Age, Continuous | 45 years STANDARD_DEVIATION 10.4 | 45 years STANDARD_DEVIATION 10.3 | 44 years STANDARD_DEVIATION 10.2 |
| CD4 Cell Count | 711 cells/μL STANDARD_DEVIATION 278.9 | 709 cells/μL STANDARD_DEVIATION 271.7 | 707 cells/μL STANDARD_DEVIATION 264.7 |
| CD4 Cell Count Category ≥ 200 to < 350 cells/µL | 10 Participants | 26 Participants | 16 Participants |
| CD4 Cell Count Category ≥ 350 to < 500 cells/µL | 52 Participants | 102 Participants | 50 Participants |
| CD4 Cell Count Category ≥ 500 cells/ µL | 249 Participants | 496 Participants | 247 Participants |
| CD4 Cell Count Category ≥ 50 to < 200 cells/µL | 5 Participants | 6 Participants | 1 Participants |
| HIV-1 RNA Category < 50 copies/mL | 307 Participants | 619 Participants | 312 Participants |
| HIV-1 RNA Category ≥ 50 copies/mL | 9 Participants | 11 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants | 24 Participants | 17 Participants |
| Race/Ethnicity, Customized Black | 65 Participants | 119 Participants | 54 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 40 Participants | 93 Participants | 53 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 275 Participants | 536 Participants | 261 Participants |
| Race/Ethnicity, Customized Not Permitted | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 10 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 238 Participants | 473 Participants | 235 Participants |
| Region of Enrollment Belgium | 5 Participants | 9 Participants | 4 Participants |
| Region of Enrollment Canada | 24 Participants | 35 Participants | 11 Participants |
| Region of Enrollment France | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Germany | 27 Participants | 57 Participants | 30 Participants |
| Region of Enrollment Italy | 3 Participants | 11 Participants | 8 Participants |
| Region of Enrollment Netherlands | 3 Participants | 7 Participants | 4 Participants |
| Region of Enrollment Spain | 15 Participants | 30 Participants | 15 Participants |
| Region of Enrollment Sweden | 2 Participants | 4 Participants | 2 Participants |
| Region of Enrollment Switzerland | 4 Participants | 8 Participants | 4 Participants |
| Region of Enrollment United Kingdom | 10 Participants | 19 Participants | 9 Participants |
| Region of Enrollment United States | 222 Participants | 448 Participants | 226 Participants |
| Sex: Female, Male Female | 41 Participants | 66 Participants | 25 Participants |
| Sex: Female, Male Male | 275 Participants | 564 Participants | 289 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 316 | 2 / 314 | 0 / 19 | 0 / 17 |
| other Total, other adverse events | 249 / 316 | 234 / 314 | 14 / 19 | 11 / 17 |
| serious Total, serious adverse events | 36 / 316 | 29 / 314 | 1 / 19 | 0 / 17 |
Outcome results
Primary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the US FDA-defined snapshot algorithm, which defines a patient'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
Population: The Full Analysis Set included participants who were randomized and received at least 1 dose of study drug and were on FTC/RPV/TDF prior to the screening visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FTC/RPV/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | 93.7 percentage of participants |
| FTC/RPV/TDF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | 93.9 percentage of participants |
Comparison: The null hypothesis was that the percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 in the FTC/RPV/TAF group was at least 8% lower than the rate in the FTC/RPV/TDF group; the alternative hypothesis was that the percentage of participants with HIV-1 RNA \< 50 copies/mL in the FTC/RPV/TAF group was less than 8% lower than that in the FTC/RPV/TDF group.95.001% CI: [-4.2, 3.7]
p-value: 1Fisher Exact
Secondary
Change From Baseline in CD4+ Cell Count at Week 48
Time frame: Baseline; Week 48
Population: Participants in the Full Analysis Set with on-treatment data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FTC/RPV/TAF | Change From Baseline in CD4+ Cell Count at Week 48 | 9 cells/µL | Standard Deviation 159.7 |
| FTC/RPV/TDF | Change From Baseline in CD4+ Cell Count at Week 48 | -1 cells/µL | Standard Deviation 152.7 |
Secondary
Change From Baseline in CD4+ Cell Count at Week 96
Time frame: Baseline; Week 96
Population: Participants in the Full Analysis Set with on-treatment data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FTC/RPV/TAF | Change From Baseline in CD4+ Cell Count at Week 96 | 12 cells/µL | Standard Deviation 180.6 |
| FTC/RPV/TDF | Change From Baseline in CD4+ Cell Count at Week 96 | 16 cells/µL | Standard Deviation 171.9 |
Secondary
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient'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
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FTC/RPV/TAF | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | 0.6 percentage of participants |
| FTC/RPV/TDF | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | 0 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a patient'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 96
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FTC/RPV/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm | 89.2 percentage of participants |
| FTC/RPV/TDF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm | 88.5 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a patient'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 96
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FTC/RPV/TAF | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm | 0.6 percentage of participants |
| FTC/RPV/TDF | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm | 1.0 percentage of participants |
Secondary
Percent Change From Baseline in Hip BMD at Week 96
Hip BMD was assessed by DXA scan.
Time frame: Baseline; Week 96
Population: Participants in the Hip DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FTC/RPV/TAF | Percent Change From Baseline in Hip BMD at Week 96 | 1.623 percentage change | Standard Deviation 2.4575 |
| FTC/RPV/TDF | Percent Change From Baseline in Hip BMD at Week 96 | -0.613 percentage change | Standard Deviation 2.7411 |
Secondary
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.
Time frame: Baseline; Week 48
Population: Participants in the Hip DXA Analysis Set (all randomized participants who received at least 1 dose of study drug, and had nonmissing baseline hip BMD value) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FTC/RPV/TAF | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 | 1.040 percentage change | Standard Deviation 1.9404 |
| FTC/RPV/TDF | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 | -0.245 percentage change | Standard Deviation 2.0805 |
Secondary
Percent Change From Baseline in Spine BMD at Week 48
Spine BMD was assessed by DXA scan.
Time frame: Baseline; Week 48
Population: Participants in the spine DXA Analysis Set (all randomized participants who received at least 1 dose of study drug, and had nonmissing baseline hip BMD value) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FTC/RPV/TAF | Percent Change From Baseline in Spine BMD at Week 48 | 1.613 percentage change | Standard Deviation 3.4346 |
| FTC/RPV/TDF | Percent Change From Baseline in Spine BMD at Week 48 | 0.075 percentage change | Standard Deviation 2.9605 |
Secondary
Percent Change From Baseline in Spine BMD at Week 96
Spine BMD was assessed by DXA scan.
Time frame: Baseline; Week 96
Population: Participants in the Spine DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FTC/RPV/TAF | Percent Change From Baseline in Spine BMD at Week 96 | 2.039 percentage change | Standard Deviation 3.5098 |
| FTC/RPV/TDF | Percent Change From Baseline in Spine BMD at Week 96 | -0.250 percentage change | Standard Deviation 3.5903 |