Study to Evaluate Switching From a Regimen of Two Nucleos(t)Ide Reverse Transcriptase Inhibitors (NRTI) Plus a Third Agent to a Fixed Dose Combination (FDC) of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF), in Virologically-Suppressed, HIV-1 Infected African American Participants
- Conditions
- HIV-1 Infection
- Interventions
- Drug: B/F/TAFDrug: NRTIsDrug: Third Agent
- Registration Number
- NCT03631732
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to evaluate the efficacy of switching from a regimen of 2 nucleos(t)Ide reverse transcriptase inhibitors (NRTIs) and a third agent to a fixed dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing their baseline regimen in HIV-1 infected, virologically suppressed African American participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 496
- Self-describes as Black, African American, or mixed race, including Black
- Currently receiving an antiretrovirals (ARV) regimen other than FDC of B/F/TAF that consists of any two NRTIs + allowed 3rd agent for ≥ 6 months
- Allowed 3rd agents include any FDA-approved INSTI, with the exception of bictegravir, any FDA-approved NNRTI with the exception of etravirine, protease inhibitors or the CCR5 antagonist, maraviroc
- If the baseline 3rd agent is dolutegravir, dosing other than 50 mg once daily is excluded
- Baseline regimens containing investigational drugs or > 2 classes of ARVs are not permitted, with the exception of the pharmacologic enhancers cobicistat (taken with elvitegravir or a PI), or ritonavir (taken with a PI)
- Have no documented or suspected resistance to INSTIs and no history of virologic failure on an INSTI containing regimen (2 consecutive HIV-1 RNA ≥ 50 copies/mL after achieving <50 copies/mL while on an INSTI-containing regimen)
- History of 1-2 thymidine analogue mutations (TAMs), M184V/I, and any other RT substitutions are allowed, with the following exceptions: History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT will be excluded
- Documented plasma HIV-1 RNA < 50 copies/mL during treatment with the baseline regimen for a minimum period of 6 months and at least the last two HIV-1 RNA measurements prior to the Screening visit
- HIV-1 RNA levels < 50 copies/mL at Screening
- Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
Key
- History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R),T69-insertions, or K65R/E/N in RT
- No desire to switch from current ARVs
- An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening
- Participants experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal bleeding)
- 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 (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
- Malignancy within 5 years of screening other than cutaneous Kaposi's sarcoma, completely resected non -melanoma skin cancer (basal cell carcinoma or non-invasive cutaneous squamous carcinoma), or completely resected carcinoma in-situ of the cervix (CIN 3) or anus (AIN 3). A prior malignancy treated with curative therapy and for which there has been no evidence of disease for at least five years prior to screening is allowed
- Current alcohol or substance use judged by the Investigator to potentially interfere with participant study compliance
- Active, serious infections (other than HIV-1 infection) requiring antibiotic or antifungal therapy within 30 days prior to Day 1
- Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
- Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with the dosing requirements
- Known hypersensitivity to FDC of B/F/TAF tablets, their metabolites, or formulation excipient
- Females who are pregnant (as confirmed by positive serum pregnancy test)
- Females who are breastfeeding
- Acute hepatitis in the 30 days prior to randomization
- Active tuberculosis infection.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Stay on Baseline Regimen (SBR)/ Delayed B/F/TAF NRTIs Participants will stay on baseline regimen consisting of 2 NRTIs and a third agent (each taken as prescribed) for 24 weeks with a delayed switch to B/F/TAF (50/200/25 mg) FDC tablet administered orally, once daily until Week 48 without regard to food. At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an additional 24 weeks or until they have access to B/F/TAF, whichever occurs first. Stay on Baseline Regimen (SBR)/ Delayed B/F/TAF Third Agent Participants will stay on baseline regimen consisting of 2 NRTIs and a third agent (each taken as prescribed) for 24 weeks with a delayed switch to B/F/TAF (50/200/25 mg) FDC tablet administered orally, once daily until Week 48 without regard to food. At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an additional 24 weeks or until they have access to B/F/TAF, whichever occurs first. B/F/TAF B/F/TAF Participants will receive B/F/TAF (50/200/25 mg) FDC tablet orally once daily for 48 weeks, without regard to food. At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an additional 24 weeks or until they have access to B/F/TAF, whichever occurs first. Stay on Baseline Regimen (SBR)/ Delayed B/F/TAF B/F/TAF Participants will stay on baseline regimen consisting of 2 NRTIs and a third agent (each taken as prescribed) for 24 weeks with a delayed switch to B/F/TAF (50/200/25 mg) FDC tablet administered orally, once daily until Week 48 without regard to food. At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an additional 24 weeks or until they have access to B/F/TAF, whichever occurs first.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Had HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set Week 24 The percentage of participants who had HIV-1 RNA ≥ 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defined 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
Name Time Method Percentage of Participants Who Had HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set Week 48 The percentage of participants who had HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defined 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. By Week 48, participants in B/F/TAF had received 48 weeks of treatment with B/F/TAF, while those in the Delayed B/F/TAF group had received only 24 weeks of treatment with B/F/TAF.
Change From Baseline in CD4+ Cell Count at Week 24: Full Analysis Set Baseline to Week 24 The analysis includes values up to 1 day after permanent discontinuation of study treatment.
Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormalities First B/F/TAF dose date up to Week 72 plus 30 days Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. Severity grades were defined by 'Gilead Grading Scale for Severity of AEs and Laboratory Abnormalities'.
Percentage of Participants Who Had HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm: Week 24 Per Protocol Analysis Set Week 24 The percentage of participants who had HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defined 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 24: Week 24 Per Protocol Analysis Set Baseline to Week 24 The analysis includes values up to 1 day after permanent discontinuation of study treatment.
Percentage of Participants Who Had HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set Week 48 The percentage of participants who had HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defined 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. By Week 48, participants in B/F/TAF had received 48 weeks of treatment with B/F/TAF, while those in the Delayed B/F/TAF group had received only 24 weeks of treatment with B/F/TAF.
Percentage of Participants Who Had HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set Week 24 The percentage of participants who had HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defined 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: Full Analysis Set Baseline to Week 48 The analysis includes values up to 1 day after permanent discontinuation of study treatment. By Week 48, participants in B/F/TAF had received 48 weeks of treatment with B/F/TAF, while those in the Delayed B/F/TAF group had received only 24 weeks of treatment with B/F/TAF.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events First B/F/TAF dose date up to Week 72 plus 30 days An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal product, which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A treatment-emergent adverse event was defined as any adverse event with onset date on or after the study treatment start date and no later than 30 days after the study drug stop date; or any adverse event leading to study drug discontinuation.
Trial Locations
- Locations (81)
Whitman-Walker Health
🇺🇸Washington, District of Columbia, United States
University Medical Center- New Orleans (UMCNO)
🇺🇸New Orleans, Louisiana, United States
Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
The GW Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Augusta University Medical Center
🇺🇸Augusta, Georgia, United States
Chatham County Health Department
🇺🇸Savannah, Georgia, United States
G.V. 'Sonny' Montgomery VAMC
🇺🇸Jackson, Mississippi, United States
Prime Healthcare Services- St. Michael's LLC d/b/a Saint Michael's Medical Center
🇺🇸Newark, New Jersey, United States
North Texas Infectious Diseases Consultants, P.A.
🇺🇸Dallas, Texas, United States
Ruane Clinical Research Group Inc.
🇺🇸Los Angeles, California, United States
Mercer University, Department of Internal Medicine
🇺🇸Macon, Georgia, United States
Capital Medical Associates, PC
🇺🇸Washington, District of Columbia, United States
AIDS Healthcare Foundation - South Beach
🇺🇸Miami Beach, Florida, United States
Southampton Clinical Research
🇺🇸Saint Louis, Missouri, United States
Alabama Medical Group, PC
🇺🇸Mobile, Alabama, United States
Triple O Research Institute, P.A.
🇺🇸West Palm Beach, Florida, United States
NorthStar Medical Center
🇺🇸Chicago, Illinois, United States
AIDS Research & Treatment Center of the Treasure Coast
🇺🇸Vero Beach, Florida, United States
Rosedale Infectious Diseases
🇺🇸Huntersville, North Carolina, United States
Southampton Healthcare, Inc.
🇺🇸Saint Louis, Missouri, United States
Mills Clinical Research
🇺🇸Los Angeles, California, United States
Gary J. Richmond, M.D., P.A.
🇺🇸Fort Lauderdale, Florida, United States
Emory Hospital Midtown Infectious Disease Clinic
🇺🇸Atlanta, Georgia, United States
Highland Hospital- Alameda Health System
🇺🇸Oakland, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Atlanta ID Group, PC
🇺🇸Atlanta, Georgia, United States
NC TraCS Institute-CTRC; University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Midway Immunology and Research Center
🇺🇸Fort Pierce, Florida, United States
St. Hope Foundation
🇺🇸Bellaire, Texas, United States
Dupont Circle Physician's Group
🇺🇸Washington, District of Columbia, United States
Infectious Disease Specialist of Atlanta
🇺🇸Decatur, Georgia, United States
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
Philadelphia FIGHT Community Health Centers
🇺🇸Philadelphia, Pennsylvania, United States
Washington Health Institute
🇺🇸Washington, District of Columbia, United States
UT Physicians
🇺🇸Charlotte, North Carolina, United States
St. John Newland Medical Associates
🇺🇸Southfield, Michigan, United States
Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Tarrant County Infectious Disease Associates
🇺🇸Fort Worth, Texas, United States
AHF
🇺🇸Pensacola, North Carolina, United States
North Shore University Hospital/Division of Infectious Diseases
🇺🇸Manhasset, New York, United States
East Carolina University, The Brody School of Medicine, ECU Adult Specialty Care
🇺🇸Greenville, North Carolina, United States
Central Texas Clinical Research
🇺🇸Austin, Texas, United States
AIDS Arms, Inc. DBA Prism Health North Texas
🇺🇸Dallas, Texas, United States
Community Health Care, Hilltop Medical Clinic
🇺🇸Tacoma, Washington, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Boston University Medical Center
🇺🇸Boston, Massachusetts, United States
Therapeutic Concepts, PA
🇺🇸Houston, Texas, United States
Research Access Network
🇺🇸Houston, Texas, United States
The Crofoot Research Center, INC (dba Gordon E. Crofoot MD PA)
🇺🇸Houston, Texas, United States
AHF- The Kinder Medical Group
🇺🇸Miami, Florida, United States
Indiana CTSI Clinical Research Center
🇺🇸Indianapolis, Indiana, United States
Huntridge Family Clinic
🇺🇸Las Vegas, Nevada, United States
Kaiser Permanente, Department of Infectious Diseases
🇺🇸San Leandro, California, United States
Hennepin County Medical Center, Positive Care Clinic
🇺🇸Minneapolis, Minnesota, United States
Duke University Health System
🇺🇸Durham, North Carolina, United States
University of Cincinnati College of Medicine
🇺🇸Cincinnati, Ohio, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Wayne State University- Integrative Bioscience Center
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Midland Florida Clinical Research Center, LLC
🇺🇸DeLand, Florida, United States
Therafirst Medical Center
🇺🇸Fort Lauderdale, Florida, United States
University of Miami School of Medicine Division of Infectious Disease
🇺🇸Miami, Florida, United States
Howard Brown Health Center
🇺🇸Chicago, Illinois, United States
CrescentCare Health
🇺🇸New Orleans, Louisiana, United States
SLVHCS Building J, 7th floor, Outpatient Infectious Disease Clinic
🇺🇸New Orleans, Louisiana, United States
Claudia T. Martorell, MD, LLC d/b/a The Research Institute
🇺🇸Springfield, Massachusetts, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Clinical: Saint Louis University, New Hope Clinic
🇺🇸Saint Louis, Missouri, United States
Jacobi Medical Center
🇺🇸Bronx, New York, United States
Thomas Street Health Center
🇺🇸Houston, Texas, United States
Palmetto Health Richland
🇺🇸Columbia, South Carolina, United States
DCOL Center for Clinical Research
🇺🇸Longview, Texas, United States
St. Joseph's Hospital Comprehensive Research Institute
🇺🇸Tampa, Florida, United States
Kaiser Permanente
🇺🇸Sacramento, California, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
One Community Health
🇺🇸Sacramento, California, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States