Acquired Immunodeficiency Syndrome, HIV Infections
Conditions
Keywords
HIV-1, HIV, Treatment Experienced
Brief summary
This study will evaluate the efficacy of Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF)) single-tablet regimen (STR) after switching from a regimen consisting of raltegravir plus Truvada® (FTC/TDF) at baseline in maintaining HIV-1 RNA \< 50 copies/mL at Week 12 in virologically suppressed, HIV-1 infected adults. This study will also evaluate the safety, tolerability, and efficacy of Stribild over 24 and 48 weeks of treatment.
Interventions
DRUGStribild
Elvitegravir (EVG) 150 mg/cobicistat (COBI) 150 mg/emtricitabine (FTC) 200 mg/tenofovir disoproxil fumarate (TDF) 300 mg single-tablet regimen (STR) administered orally once daily with food
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to understand and sign a written informed consent form * Virologically stable on the current first antiretroviral regimen consisting only of raltegravir twice daily plus FTC/TDF continuously for ≥ 6 months preceding the screening visit and * have documented undetectable plasma HIV-1 RNA levels ≥ 6 months preceding the screening visit (measured at least twice using the same assay) and * have never experienced two consecutive HIV-1 RNA above detectable levels after first achieving a confirmed HIV-1 RNA level below detectable levels on the first regimen * HIV-1 RNA \< 50 copies/mL at the screening visit * Have a genotype prior to starting initial antiretroviral therapy and have no known resistance to any of the study agents at any time * Normal ECG * Hepatic transaminases ≤ 5 x upper limit of normal (ULN) * Total bilirubin ≤ 1.5 mg/dL * Adequate hematologic function * Serum amylase ≤ 5 x ULN * Estimated glomerular filtration rate ≥ 70 mL/min * Females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active, practice sexual abstinence or have a vasectomized partner from screening throughout the duration of the study period and for 30 days following the last dose of study drug * Females 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 * Males must agree to utilize a highly effective method of contraception during heterosexual intercourse from the screening visit, throughout the duration of the study and for 30 days following discontinuation of investigational medicinal product or must be non heterosexually active, practice sexual abstinence, or be vasectomized
Exclusion criteria
* New AIDS defining condition diagnosed within the 21 days prior to screening * Females who are breastfeeding * Positive serum pregnancy test (female of childbearing potential) * Individuals with acute or chronic hepatitis B or hepatitis C co-infection * Individuals experiencing decompensated cirrhosis * Have an implanted defibrillator or pacemaker * Current alcohol or substance abuse that would interfere with compliance * A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma * Active, serious infections requiring parenteral antibiotic or antifungal therapy within 21 days prior to the baseline visit * Receiving any investigational drugs * Participation in any other clinical trial without prior approval from the sponsor * 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 * Any other clinical condition or prior therapy that would make the individual unsuitable for the study or unable to comply with the dosing requirements * Receiving ongoing therapy or anticipated to need to initiate drugs or herbal/natural supplements during the study that are contraindicated or not recommended for use, including drugs not to be used with Stribild; or individuals with known allergies to the excipients of the Stribild single tablet regimen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 | Week 12 | The FDA-defined Snapshot algorithm was used, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) and Graded Laboratory Abnormalities | Up to 48 weeks plus 30 days | This outcome measure assessed the safety and tolerability profile of Stribild. Treatment-emergent adverse events (AEs) and graded laboratory abnormalities occurring from baseline up to 30 days following the last dose of study drug were summarized. |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 | Weeks 24 and 48 | The FDA-defined Snapshot algorithm was used, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at a total of 7 study sites in the United States. The first participant was screened on 31 January 2012. The last study visit occurred on 23 August 2013.
Pre-assignment details
58 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Stribild Switch from existing treatment regimen to Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily for 48 weeks | 48 |
| Total | 48 |
Baseline characteristics
| Characteristic | Stribild |
|---|---|
| Age, Continuous | 44 years STANDARD_DEVIATION 8.6 |
| Baseline HIV-1 RNA Category < 50 copies/mL | 46 participants |
| Baseline HIV-1 RNA Category 50 to < 200 copies/mL | 2 participants |
| CD4 Cell Count | 711 cells/µL STANDARD_DEVIATION 265.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HIV Disease Status AIDS | 2 participants |
| HIV Disease Status Asymptomatic | 45 participants |
| HIV Disease Status Symptomatic HIV Infection | 1 participants |
| Race/Ethnicity, Customized Asian | 1 participants |
| Race/Ethnicity, Customized Black or African American | 7 participants |
| Race/Ethnicity, Customized White | 40 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 33 / 48 |
| serious Total, serious adverse events | 1 / 48 |
Outcome results
Primary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12
The FDA-defined Snapshot algorithm was used, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time.
Time frame: Week 12
Population: Full Analysis Set: participants who received at least one dose of study drug and had no major protocol violations of study drug resistance at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stribild | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 | 100.0 percentage of participants |
Secondary
Percentage of Participants With Adverse Events (AEs) and Graded Laboratory Abnormalities
This outcome measure assessed the safety and tolerability profile of Stribild. Treatment-emergent adverse events (AEs) and graded laboratory abnormalities occurring from baseline up to 30 days following the last dose of study drug were summarized.
Time frame: Up to 48 weeks plus 30 days
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stribild | Percentage of Participants With Adverse Events (AEs) and Graded Laboratory Abnormalities | Any AE | 89.6 percentage of participants |
| Stribild | Percentage of Participants With Adverse Events (AEs) and Graded Laboratory Abnormalities | Drug-related AE | 25.0 percentage of participants |
| Stribild | Percentage of Participants With Adverse Events (AEs) and Graded Laboratory Abnormalities | Grade 3 or higher AE | 4.2 percentage of participants |
| Stribild | Percentage of Participants With Adverse Events (AEs) and Graded Laboratory Abnormalities | Serious AE | 2.1 percentage of participants |
| Stribild | Percentage of Participants With Adverse Events (AEs) and Graded Laboratory Abnormalities | Any laboratory abnormality | 91.7 percentage of participants |
| Stribild | Percentage of Participants With Adverse Events (AEs) and Graded Laboratory Abnormalities | Grade 3 or 4 laboratory abnormality | 4.2 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48
The FDA-defined Snapshot algorithm was used, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time.
Time frame: Weeks 24 and 48
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stribild | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 | Week 24 | 100.0 percentage of participants |
| Stribild | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 | Week 48 | 100.0 percentage of participants |