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 Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: B/F/TAF
* Drug: NRTIs
* Drug: Third Agent


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B/F/TAF<br>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. | Drug: B/F/TAF<br>* 50/200/25 mg FDC tablets administered orally once daily without regard to food<br>* Other names: Biktarvy®;|
| Active Comparator: Stay on Baseline Regimen (SBR)/ Delayed B/F/TAF<br>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. | Drug: B/F/TAF<br>* 50/200/25 mg FDC tablets administered orally once daily without regard to food<br>* Other names: Biktarvy®;Drug: NRTIs<br>* 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)<br>Drug: Third Agent<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 |