Acquired Immunodeficiency Syndrome, HIV Infections
Conditions
Keywords
HIV-1, HIV, Treatment-Naive
Brief summary
The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya®; E/C/F/TAF) fixed-dose combination (FDC) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild®; E/C/F/TDF) FDC in HIV-1 infected, antiretroviral treatment-naive adults.
Interventions
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Ability to understand and sign a written informed consent form * Plasma HIV 1 RNA levels ≥ 5,000 copies/mL * No prior use of any approved or experimental anti-HIV drug for any length of time * Screening genotype report must show sensitivity to TDF and emtricitabine (FTC) * Normal ECG * Adequate renal function: Estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula * Hepatic transaminases ≤ 2.5 x upper limit of the normal range (ULN) * Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin * Adequate hematologic function * CD4+ cell count \> 50 cells/µL * Serum amylase ≤ 5 x ULN * Normal thyroid-stimulating hormone (TSH) * Females of childbearing potential must have a negative serum pregnancy test * Females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drugs * Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing * Female subjects who are postmenopausal must have documentation of cessation of menses for ≥ 12 months and hormonal failure * Female subjects who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level test at screening * Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 90 days following discontinuation of investigational medicinal product * Age ≥ 18 years * Life expectancy ≥ 1 year Key
Exclusion criteria
* New AIDS-defining condition diagnosed within the 30 days prior to screening * Hepatitis B surface Antigen positive * Hepatitis C Antibody positive * Proven acute hepatitis in the 30 days prior to study entry * Subjects experiencing decompensated cirrhosis * Females who are breastfeeding * Positive serum pregnancy test (female of childbearing potential) * Have an implanted defibrillator or pacemaker * Receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with elvitegravir and cobicistat * Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study * Current alcohol or substance * History of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma or resected, non-invasive cutaneous squamous carcinoma * Active, serious infections (other than HIV 1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline * Participation in any other clinical trial without prior approval is prohibited while participating in this trial * Medications contraindicated for use with emtricitabine or tenofovir disoproxil fumarate * Any known allergies to the excipients of E/C/F/TAF or E/C/F/TDF FDC tablets * Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 | Week 24 | The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | 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 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. |
| Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48 | Baseline; Weeks 24 and 48 | — |
| Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 | Baseline; Weeks 24 and 48 | — |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States and Puerto Rico. The first participant was screened on 28 December 2011. The last study visit occurred on 22 August 2016.
Pre-assignment details
232 participants were screened for the Double-Blind Phase. 108 participants from other Gilead-sponsored Study GS-US-299-0102 joined the Open-Label Extension Phase.
Participants by arm
| Arm | Count |
|---|---|
| E/C/F/TAF Double-Blind Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet plus E/C/F/TDF placebo tablet administered orally once daily for 48 weeks
Open-Label (OL) Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily | 112 |
| E/C/F/TDF Double-Blind Phase: E/C/F/TDF (150/150/200/300 mg) FDC tablet plus E/C/F/TAF placebo tablet administered orally once daily for 48 weeks
Open-Label Extension Phase: E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily | 58 |
| D/C/F/TAF to Open-Label E/C/F/TAF Participants previously received D/C/F/TAF in another Gilead-sponsored study and then enrolled into the Open-Label Extension Phase of this study to receive E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily. | 70 |
| DRV+COBI+TVD to Open-Label E/C/F/TAF Participants previously received DRV+COBI+TVD in another Gilead-sponsored study and then enrolled into the Open-Label Extension Phase of this study to receive E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily. | 38 |
| Total | 278 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-Blind Phase | Adverse Event | 1 | 0 | 0 | 0 |
| Double-Blind Phase | Investigator's Discretion | 1 | 0 | 0 | 0 |
| Double-Blind Phase | Lack of Efficacy | 0 | 1 | 0 | 0 |
| Double-Blind Phase | Lost to Follow-up | 3 | 2 | 0 | 0 |
| Double-Blind Phase | Randomized but not Treated | 1 | 0 | 0 | 0 |
| Double-Blind Phase | Subject Non-Compliance | 0 | 1 | 0 | 0 |
| Double-Blind Phase | Withdrew Consent | 0 | 1 | 0 | 0 |
| Open-Label Extension Phase | Adverse Event | 1 | 0 | 0 | 0 |
| Open-Label Extension Phase | Death | 1 | 0 | 0 | 0 |
| Open-Label Extension Phase | Lost to Follow-up | 9 | 3 | 5 | 5 |
| Open-Label Extension Phase | Pregnancy | 0 | 1 | 1 | 0 |
| Open-Label Extension Phase | Protocol Violation | 0 | 0 | 1 | 0 |
| Open-Label Extension Phase | Withdrew Consent | 8 | 3 | 2 | 0 |
Baseline characteristics
| Characteristic | E/C/F/TAF | E/C/F/TDF | D/C/F/TAF to Open-Label E/C/F/TAF | DRV+COBI+TVD to Open-Label E/C/F/TAF | Total |
|---|---|---|---|---|---|
| Age, Continuous | 35 years STANDARD_DEVIATION 11.3 | 37 years STANDARD_DEVIATION 10.6 | 36 years STANDARD_DEVIATION 11.2 | 37 years STANDARD_DEVIATION 10.7 | 36 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 3 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 108 Participants | 57 Participants | 67 Participants | 35 Participants | 267 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 91 / 112 | 48 / 58 | 215 / 273 |
| serious Total, serious adverse events | 12 / 112 | 3 / 58 | 35 / 273 |
Outcome results
Primary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 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 24
Population: Full Analysis Set: participants randomized to the Double-Blind Phase and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 | 88.4 percentage of participants |
| E/C/F/TDF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 | 89.7 percentage of participants |
p-value: 0.5895% CI: [-13.5, 7.7]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in CD4+ Cell Count at Weeks 24 and 48
Time frame: Baseline; Weeks 24 and 48
Population: Participants in Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E/C/F/TAF | Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 | Baseline | 404 cells/uL | Standard Deviation 181.6 |
| E/C/F/TAF | Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 | Change at Week 24 | 165 cells/uL | Standard Deviation 115.6 |
| E/C/F/TAF | Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 | Change at Week 48 | 177 cells/uL | Standard Deviation 144.1 |
| E/C/F/TDF | Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 | Baseline | 394 cells/uL | Standard Deviation 209.6 |
| E/C/F/TDF | Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 | Change at Week 24 | 179 cells/uL | Standard Deviation 127.7 |
| E/C/F/TDF | Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 | Change at Week 48 | 204 cells/uL | Standard Deviation 120.4 |
Secondary
Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48
Time frame: Baseline; Weeks 24 and 48
Population: Participants in Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E/C/F/TAF | Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48 | Baseline | 4.63 log10 copies/mL | Standard Deviation 0.572 |
| E/C/F/TAF | Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48 | Change at Week 24 | -3.20 log10 copies/mL | Standard Deviation 0.654 |
| E/C/F/TAF | Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48 | Change at Week 48 | -3.22 log10 copies/mL | Standard Deviation 0.606 |
| E/C/F/TDF | Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48 | Baseline | 4.69 log10 copies/mL | Standard Deviation 0.577 |
| E/C/F/TDF | Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48 | Change at Week 24 | -3.26 log10 copies/mL | Standard Deviation 0.606 |
| E/C/F/TDF | Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48 | Change at Week 48 | -3.33 log10 copies/mL | Standard Deviation 0.572 |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 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 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: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E/C/F/TAF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | 88.4 percentage of participants |
| E/C/F/TDF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | 87.9 percentage of participants |