A Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults
Overview
- Phase
- Phase 3
- Intervention
- E/C/F/TAF
- Conditions
- HIV-1
- Sponsor
- Gilead Sciences
- Enrollment
- 158
- Locations
- 62
- Primary Endpoint
- Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 24
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed dose combination (FDC) plus darunavir (DRV) relative to current antiretroviral regimens (ARV) in virologically suppressed, HIV-1 positive participants with HIV-1 RNA <50 copies/mL at Week 24.
This study consists of 48 weeks of open-label phase followed by an optional Extension Phase in which all the participants will receive E/C/F/TAF+DRV.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Ability to understand and sign a written informed consent form
- •History of at least two prior antiretroviral regimens, and history of resistance to at least two different classes of antiretroviral agents
- •Plasma HIV-1 RNA levels \< 50 copies/mL at screening. Virologically suppressed on the current antiretroviral regimen containing darunavir 600 mg twice a day or 800 mg once daily continuously for ≥ 4 months preceding the screening visit and have maintained documented undetectable plasma HIV-1 RNA levels (\< 50 copies/mL) and must have documentation of genotype/phenotype prior to current regimen which shows no darunavir associated resistance mutation.
- •Currently receiving raltegravir, elvitegravir, or dolutegravir (50 mg once daily, but not twice daily), or have never received integrase inhibitor, or have documentation of genotype/phenotype within 12 months prior to current regimen which must show no evidence of resistance to integrase inhibitors
- •Normal ECG
- •Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft Gault formula for creatinine clearance
- •Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
- •Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
- •Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm\^3; platelets ≥ 50,000/mm\^3; hemoglobin ≥ 8.5 g/dL)
- •Serum amylase ≤ 5 × ULN (individuals with serum amylase \> 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
Exclusion Criteria
- •A new AIDS-defining condition diagnosed within the 30 days prior to screening (except CD4 cell count and/or percentage criteria)
- •Hepatitis B surface antigen (HBsAg) positive
- •Individuals receiving drug treatment for Hepatitis C, or individuals who are anticipated to receive treatment for Hepatitis C during the course of the study.
- •Must not have Q151M, T69ins, or \> 3 thymidine analogue mutations (TAMS) present on documented historic genotype report
- •Individuals experiencing decompensated cirrhosis
- •Females who are breastfeeding
- •Positive serum pregnancy test
- •Have an implanted defibrillator or pacemaker
- •Current alcohol or substance use that may interfere with individual's study compliance
- •A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma.
Arms & Interventions
Cohort 1
Participants will receive E/C/F/TAF FDC + DRV once daily with food for 48 weeks. Based on safety and efficacy data from Cohort 1 at Week 4, the participants will be randomized into Cohort 2. The participants in Cohort 1 will continue receiving E/C/F/TAF FDC + DRV through 48 weeks.
Intervention: E/C/F/TAF
Cohort 1
Participants will receive E/C/F/TAF FDC + DRV once daily with food for 48 weeks. Based on safety and efficacy data from Cohort 1 at Week 4, the participants will be randomized into Cohort 2. The participants in Cohort 1 will continue receiving E/C/F/TAF FDC + DRV through 48 weeks.
Intervention: DRV
Cohort 2, Treatment Group 1
Participants will be randomized to receive E/C/F/TAF FDC+DRV once daily with food for 48 weeks.
Intervention: E/C/F/TAF
Cohort 2, Treatment Group 1
Participants will be randomized to receive E/C/F/TAF FDC+DRV once daily with food for 48 weeks.
Intervention: DRV
Cohort 2, Treatment Group 2
Participants will be randomized to continue on their baseline DRV-containing ARV regimen for 48 weeks.
Intervention: Baseline DRV- containing ARV regimen
Outcomes
Primary Outcomes
Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 24
Time Frame: 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 Outcomes
- Change From Baseline in CD4+ Cell Count at Week 48(Baseline; Week 48)
- Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 48(Week 48)
- Change From Baseline in CD4+ Cell Count at Week 24(Baseline; Week 24)