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

HIV-1 Infection Clinical Trial

— BRAAVE 2020  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03631732
• Other study ID #: GS-US-380-4580
• Status: Completed
• Phase: Phase 3
• Start date: August 28, 2018
• Est. completion date: August 19, 2020

Study information

• Verified date: August 2021
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 496
• Est. completion date: August 19, 2020
• Est. primary completion date: August 12, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• B/F/TAF
50/200/25 mg FDC tablets administered orally once daily without regard to food
• NRTIs
The following NRTIs will be administered as prescribed until Week 24 without regard to food: abacavir (ABC), emtricitabine (FTC), lamivudine (3TC), tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), zidovudine (ZDV or AZT)
• Third Agent
Any one of the following third agents will be administered as prescribed. Protease inhibitors and EVG will be administered with the appropriate pharmacologic booster cobicistat or ritonavir. : Non-nucleoside reverse transcriptase inhibitors (NNRTIs) delavirdine (DLV) efavirenz (EFV) nevirapine (NVP) rilpivirine (RPV) doravirine (DOR) Integrase inhibitors dolutegravir (DTG) elvitegravir (EVG) raltegravir (RAL) Protease inhibitors (PIs) atazanavir (ATV) darunavir (DRV) lopinavir (LPV) nelfinavir NFV) saquinavir (SQV) tipranavir (TPV) Chemokine co-recptor 5 (CCR5) antagonist --maraviroc (MVC)

Locations

Country	Name	City	State
United States	Atlanta ID Group, PC	Atlanta	Georgia
United States	Emory Hospital Midtown Infectious Disease Clinic	Atlanta	Georgia
United States	Augusta University Medical Center	Augusta	Georgia
United States	Central Texas Clinical Research	Austin	Texas
United States	St. Hope Foundation	Bellaire	Texas
United States	Be Well Medical Center	Berkley	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston University Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Jacobi Medical Center	Bronx	New York
United States	Montefiore Medical Center	Bronx	New York
United States	NC TraCS Institute-CTRC; University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	UT Physicians	Charlotte	North Carolina
United States	Howard Brown Health Center	Chicago	Illinois
United States	NorthStar Medical Center	Chicago	Illinois
United States	University of Cincinnati College of Medicine	Cincinnati	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Palmetto Health Richland	Columbia	South Carolina
United States	AIDS Arms, Inc. DBA Prism Health North Texas	Dallas	Texas
United States	North Texas Infectious Diseases Consultants, P.A.	Dallas	Texas
United States	Infectious Disease Specialist of Atlanta	Decatur	Georgia
United States	Midland Florida Clinical Research Center, LLC	DeLand	Florida
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University- Integrative Bioscience Center	Detroit	Michigan
United States	Duke University Health System	Durham	North Carolina
United States	Gary J. Richmond, M.D., P.A.	Fort Lauderdale	Florida
United States	Therafirst Medical Center	Fort Lauderdale	Florida
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	Tarrant County Infectious Disease Associates	Fort Worth	Texas
United States	East Carolina University, The Brody School of Medicine, ECU Adult Specialty Care	Greenville	North Carolina
United States	Research Access Network	Houston	Texas
United States	The Crofoot Research Center, INC (dba Gordon E. Crofoot MD PA)	Houston	Texas
United States	Therapeutic Concepts, PA	Houston	Texas
United States	Thomas Street Health Center	Houston	Texas
United States	Rosedale Infectious Diseases	Huntersville	North Carolina
United States	Indiana CTSI Clinical Research Center	Indianapolis	Indiana
United States	G.V. 'Sonny' Montgomery VAMC	Jackson	Mississippi
United States	Huntridge Family Clinic	Las Vegas	Nevada
United States	DCOL Center for Clinical Research	Longview	Texas
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Mills Clinical Research	Los Angeles	California
United States	Ruane Clinical Research Group Inc.	Los Angeles	California
United States	Mercer University, Department of Internal Medicine	Macon	Georgia
United States	North Shore University Hospital/Division of Infectious Diseases	Manhasset	New York
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	AHF- The Kinder Medical Group	Miami	Florida
United States	University of Miami School of Medicine Division of Infectious Disease	Miami	Florida
United States	AIDS Healthcare Foundation - South Beach	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Hennepin County Medical Center, Positive Care Clinic	Minneapolis	Minnesota
United States	Alabama Medical Group, PC	Mobile	Alabama
United States	CrescentCare Health	New Orleans	Louisiana
United States	SLVHCS Building J, 7th floor, Outpatient Infectious Disease Clinic	New Orleans	Louisiana
United States	University Medical Center- New Orleans (UMCNO)	New Orleans	Louisiana
United States	Prime Healthcare Services- St. Michael's LLC d/b/a Saint Michael's Medical Center	Newark	New Jersey
United States	Highland Hospital- Alameda Health System	Oakland	California
United States	Kaiser Permanente	Oakland	California
United States	Orlando Immunology Center	Orlando	Florida
United States	AHF	Pensacola	North Carolina
United States	Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Philadelphia FIGHT Community Health Centers	Philadelphia	Pennsylvania
United States	Kaiser Permanente	Sacramento	California
United States	One Community Health	Sacramento	California
United States	Clinical: Saint Louis University, New Hope Clinic	Saint Louis	Missouri
United States	Southampton Clinical Research	Saint Louis	Missouri
United States	Southampton Healthcare, Inc.	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Kaiser Permanente, Department of Infectious Diseases	San Leandro	California
United States	Chatham County Health Department	Savannah	Georgia
United States	St. John Newland Medical Associates	Southfield	Michigan
United States	Claudia T. Martorell, MD, LLC d/b/a The Research Institute	Springfield	Massachusetts
United States	Community Health Care, Hilltop Medical Clinic	Tacoma	Washington
United States	St. Joseph's Hospital Comprehensive Research Institute	Tampa	Florida
United States	AIDS Research & Treatment Center of the Treasure Coast	Vero Beach	Florida
United States	Capital Medical Associates, PC	Washington	District of Columbia
United States	Dupont Circle Physician's Group	Washington	District of Columbia
United States	Georgetown University Hospital	Washington	District of Columbia
United States	The GW Medical Faculty Associates	Washington	District of Columbia
United States	Washington Health Institute	Washington	District of Columbia
United States	Whitman-Walker Health	Washington	District of Columbia
United States	Triple O Research Institute, P.A.	West Palm Beach	Florida
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (5)

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.

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.

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 Blac — View 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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Week 24
Secondary	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	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.	Week 48
Secondary	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	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.	Week 24
Secondary	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	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.	Week 24
Secondary	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	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.	Week 48
Secondary	Change From Baseline in CD4+ Cell Count at Week 24: Full Analysis Set	The analysis includes values up to 1 day after permanent discontinuation of study treatment.	Baseline to Week 24
Secondary	Change From Baseline in CD4+ Cell Count at Week 24: Week 24 Per Protocol Analysis Set	The analysis includes values up to 1 day after permanent discontinuation of study treatment.	Baseline to Week 24
Secondary	Change From Baseline in CD4+ Cell Count at Week 48: Full Analysis Set	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.	Baseline to Week 48
Secondary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events	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.	First B/F/TAF dose date up to Week 72 plus 30 days
Secondary	Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormalities	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'.	First B/F/TAF dose date up to Week 72 plus 30 days