Clinical trial NCT03631732: 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
Official title: A Phase 3b, Multicenter, Open-Label 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2018-08-15
Enrollment: 496
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

* 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 Exclusion Criteria:

* 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.

Primary outcomes:
measure: 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
timeFrame: Week 24
Secondary outcomes:
measure: 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
timeFrame: Week 48
measure: 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
timeFrame: Week 24
measure: 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
timeFrame: Week 24
measure: 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
timeFrame: Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 24: Full Analysis Set
timeFrame: Baseline to Week 24
measure: Change From Baseline in CD4+ Cell Count at Week 24: Week 24 Per Protocol Analysis Set
timeFrame: Baseline to Week 24
measure: Change From Baseline in CD4+ Cell Count at Week 48: Full Analysis Set
timeFrame: Baseline to Week 48
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: First B/F/TAF dose date up to Week 72 plus 30 days
measure: Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormalities
timeFrame: First B/F/TAF dose date up to Week 72 plus 30 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Mobile
country: United States
facility: Alabama Medical Group, PC
state: Alabama
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group Inc.
state: California
city: Los Angeles
country: United States
facility: Mills Clinical Research
state: California
city: Oakland
country: United States
facility: Highland Hospital- Alameda Health System
state: California
city: Oakland
country: United States
facility: Kaiser Permanente
state: California
city: Sacramento
country: United States
facility: One Community Health
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente
state: California
city: San Leandro
country: United States
facility: Kaiser Permanente, Department of Infectious Diseases
state: California
city: Washington
country: United States
facility: Whitman-Walker Health
state: District of Columbia
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Dupont Circle Physician's Group
state: District of Columbia
city: Washington
country: United States
facility: Washington Health Institute
state: District of Columbia
city: Washington
country: United States
facility: Capital Medical Associates, PC
state: District of Columbia
city: Washington
country: United States
facility: The GW Medical Faculty Associates
state: District of Columbia
city: DeLand
country: United States
facility: Midland Florida Clinical Research Center, LLC
state: Florida
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Gary J. Richmond, M.D., P.A.
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Miami Beach
country: United States
facility: AIDS Healthcare Foundation - South Beach
state: Florida
city: Miami
country: United States
facility: AHF- The Kinder Medical Group
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine Division of Infectious Disease
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Hospital Comprehensive Research Institute
state: Florida
city: Vero Beach
country: United States
facility: AIDS Research & Treatment Center of the Treasure Coast
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A.
state: Florida
city: Atlanta
country: United States
facility: Emory Hospital Midtown Infectious Disease Clinic
state: Georgia
city: Atlanta
country: United States
facility: Atlanta ID Group, PC
state: Georgia
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialist of Atlanta
state: Georgia
city: Macon
country: United States
facility: Mercer University, Department of Internal Medicine
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Department
state: Georgia
city: Chicago
country: United States
facility: Howard Brown Health Center
state: Illinois
city: Chicago
country: United States
facility: NorthStar Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana CTSI Clinical Research Center
state: Indiana
city: New Orleans
country: United States
facility: University Medical Center- New Orleans (UMCNO)
state: Louisiana
city: New Orleans
country: United States
facility: SLVHCS Building J, 7th floor, Outpatient Infectious Disease Clinic
state: Louisiana
city: New Orleans
country: United States
facility: CrescentCare Health
state: Louisiana
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Claudia T. Martorell, MD, LLC d/b/a The Research Institute
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Detroit
country: United States
facility: Wayne State University- Integrative Bioscience Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Southfield
country: United States
facility: St. John Newland Medical Associates
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center, Positive Care Clinic
state: Minnesota
city: Jackson
country: United States
facility: G.V. 'Sonny' Montgomery VAMC
state: Mississippi
city: Saint Louis
country: United States
facility: Southampton Clinical Research
state: Missouri
city: Saint Louis
country: United States
facility: Clinical: Saint Louis University, New Hope Clinic
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Southampton Healthcare, Inc.
state: Missouri
city: Las Vegas
country: United States
facility: Huntridge Family Clinic
state: Nevada
city: Newark
country: United States
facility: Prime Healthcare Services- St. Michael's LLC d/b/a Saint Michael's Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital/Division of Infectious Diseases
state: New York
city: Chapel Hill
country: United States
facility: NC TraCS Institute-CTRC; University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: UT Physicians
state: North Carolina
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University, The Brody School of Medicine, ECU Adult Specialty Care
state: North Carolina
city: Huntersville
country: United States
facility: Rosedale Infectious Diseases
state: North Carolina
city: Pensacola
country: United States
facility: AHF
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati College of Medicine
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia FIGHT Community Health Centers
state: Pennsylvania
city: Columbia
country: United States
facility: Palmetto Health Richland
state: South Carolina
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Bellaire
country: United States
facility: St. Hope Foundation
state: Texas
city: Dallas
country: United States
facility: AIDS Arms, Inc. DBA Prism Health North Texas
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, P.A.
state: Texas
city: Fort Worth
country: United States
facility: Tarrant County Infectious Disease Associates
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Houston
country: United States
facility: Thomas Street Health Center
state: Texas
city: Houston
country: United States
facility: Research Access Network
state: Texas
city: Houston
country: United States
facility: The Crofoot Research Center, INC (dba Gordon E. Crofoot MD PA)
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Tacoma
country: United States
facility: Community Health Care, Hilltop Medical Clinic
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Andreatta K, D'Antoni ML, Chang S, Parvangada A, Martin R, Blair C, et al. Preexisting Resistance and Week 48 Virologic Outcomes after Switching to B/F/TAF in African American Adults With HIV [Presentation]. IDWeek Virtual; 2020b 21-25 October.
citation: Hagins D, Kumar P, Saag M, Wurapa AK, Brar I, Berger D, Osiyemi O, Hileman CO, Ramgopol M, McDonald C, Blair C, Andreatta K, Collins SE, Brainard D, Martin H. Week-48 Outcomes From the BRAAVE 2020 Study: a Randomized Switch to B/F/TAF in African-American Adults With HIV, IDWeek 2020, October 21-25. Abstract 1046.
citation: Andreatta K, D'Antoni ML, Chang S, Martin R, Blair C, Collins SE, et al. Preexisting Resistance and B/F/TAF Switch Efficacy in African Americans [Poster 509]. Conference on Retroviruses and Opportunistic Infections (CROI); 2020b 08-11 March; Boston, MA.
citation: Hagins D, Kumar P, Saag M, Wurapa AK, Brar I, Berger D, Osiyemi O, Hileman CO, Ramgopol M, McDonald C, Blair C, Andreatta K, Collins SE, Brainard D, Martin H. Randomized Switch to B/F/TAF in African American Adults with HIV. Conference on Retroviruses and Opportunistic Infections 2020, March 7-11, Boston MA. Abstract 2979.
citation: Hagins D, Kumar P, Saag M, Wurapa AK, Brar I, Berger D, Osiyemi O, Hileman CO, Ramgopal MN, McDonald C, Blair C, Andreatta K, Collins SE, Brainard DM, Martin H; BRAAVE2020 Investigators. Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. J Acquir Immune Defic Syndr. 2021 Sep 1;88(1):86-95. doi: 10.1097/QAI.0000000000002731.