Safety and Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment Naive, HIV-1 and Hepatitis B Co-Infected Adults

Phase 3

Completed

• Conditions: HIV-1/HBV Co-Infection
• Interventions: Drug: B/F/TAF; Drug: DTG; Drug: Placebo to match DTG; Drug: F/TDF; Drug: Placebo to match F/TDF; Drug: Placebo to match B/F/TAF

• Registration Number: NCT03547908
• Lead Sponsor: Gilead Sciences

Brief Summary

The primary objective of this study is to evaluate the efficacy of fixed-dose combination (FDC) of bictegravir/emtricitabine/ tenofovir alafenamide (B/F/TAF) versus dolutegravir (DTG) + emtricitabine/tenofovir disoproxil fumarate (F/TDF) in treatment-naïve and HIV-1 and hepatitis B virus (HBV) adults.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-05-24
• Study First Submitted QC: 2018-05-24
• Study Start: 2018-05-30
• Study First Posted: 2018-06-06
• Primary Completion: 2022-02-25
• Results First Submitted: 2023-02-17
• Results First Submitted QC: 2023-02-17
• Results First Posted: 2023-03-15
• Study Completion: 2024-03-07
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-27
• Last Update Posted: 2025-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 244

Inclusion Criteria

• Human immunodeficiency virus type 1 (HIV-1) co-infection:

  • Must be HIV antiretroviral treatment naive with plasma HIV-1 ribonucleic acid (RNA) ≥ 500 copies/mL at screening
  • ≤ 10 days of prior therapy with any antiretroviral agent, including lamivudine and entecavir, following a diagnosis of HIV-1 infection (except the use for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), up to one month prior to screening)
  • Screening genotype report must show sensitivity to emtricitabine (FTC) and tenofovir (TFV). This report will be provided by Gilead Sciences. Alternatively, if genotype results from a local laboratory obtained ≤ 90 days prior to screening visit date show sensitivity to these drugs, this genotype will be acceptable to fulfill this inclusion criterion in the event that the genotype obtained at screening is not yet available and all other inclusion/exclusion criteria have been confirmed

• HBV co-infection:

  • Must be hepatitis B virus (HBV) treatment naive (defined as < 12 weeks of oral antiviral treatment)
  • Screening HBV deoxyribonucleic acid (DNA) ≥ 2000 IU/mL

• Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) ≤ 10 x upper limit of normal (ULN)

• Total bilirubin ≤ 2.5 x ULN

Key

Exclusion Criteria

• Hepatitis C virus (HCV) antibody positive and HCV RNA detectable
• Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding) or with Child-Pugh-Turcotte (CPT) C impairment
• Current alcohol or substance use judged by the Investigator to potentially interfere with study compliance
• Active, serious infections (other than HIV-1 and HBV infection) requiring parenteral 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Blinded Phase: B/F/TAF	B/F/TAF	Participants who are HIV-1 and HBV co-infected and treatment-naïve will receive Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) fixed-dose combination (FDC) tablet in addition to placebo to match (PTM) dolutegravir (DTG) tablet and PTM FDC emtricitabine/ tenofovir desoproxil fumarate (F/TDF) tablet for 96 weeks.
Blinded Phase: B/F/TAF	Placebo to match DTG	Participants who are HIV-1 and HBV co-infected and treatment-naïve will receive Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) fixed-dose combination (FDC) tablet in addition to placebo to match (PTM) dolutegravir (DTG) tablet and PTM FDC emtricitabine/ tenofovir desoproxil fumarate (F/TDF) tablet for 96 weeks.
Blinded Phase: B/F/TAF	Placebo to match F/TDF	Participants who are HIV-1 and HBV co-infected and treatment-naïve will receive Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) fixed-dose combination (FDC) tablet in addition to placebo to match (PTM) dolutegravir (DTG) tablet and PTM FDC emtricitabine/ tenofovir desoproxil fumarate (F/TDF) tablet for 96 weeks.
Blinded Phase: DTG+F/TDF	DTG	Participants who are HIV-1 and HBV co-infected and treatment-naïve will receive DTG and FDC F/TDF in addition to PTM B/F/TAF for 96 weeks.
Blinded Phase: DTG+F/TDF	F/TDF	Participants who are HIV-1 and HBV co-infected and treatment-naïve will receive DTG and FDC F/TDF in addition to PTM B/F/TAF for 96 weeks.
Blinded Phase: DTG+F/TDF	Placebo to match B/F/TAF	Participants who are HIV-1 and HBV co-infected and treatment-naïve will receive DTG and FDC F/TDF in addition to PTM B/F/TAF for 96 weeks.
Open-label Extension Phase: B/F/TAF from B/F/TAF	B/F/TAF	After Week 96, participants will continue to take their blinded study drug and attend visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants in a country where B/F/TAF FDC is not available will be given the option to receive B/F/TAF FDC in an open-label extension phase for up to 48 weeks, or until the product becomes accessible through an access program, or until Gilead elects to discontinue the study in that country, whichever occurs first.
Open-label Extension Phase: B/F/TAF from DTG+F/TDF	B/F/TAF	After Week 96, participants will continue to take their blinded study drug and attend visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants in a country where B/F/TAF FDC is not available will be given the option to receive B/F/TAF FDC in an open-label extension phase for up to 48 weeks, or until the product becomes accessible through an access program, or until Gilead elects to discontinue the study in that country, whichever occurs first.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm (Co-primary Endpoint)	Week 48	The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines 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. Percentages were rounded-off.
Percentage of Participants With Plasma Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48 as Defined by Missing = Failure Approach (Co-primary Endpoint)	Week 48	This outcome measure was analyzed using a Missing = Failure approach. In this approach, all missing data were treated as HBV DNA ≥ 29 IU/mL. Percentages were rounded-off.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With ALT Normalization at Week 96	Week 96	ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given post baseline visit. The upper limit of the normal range (ULN) for ALT using the 2018 AASLD normal range was ≤ 25 U/L for females and ≤ 35 U/L for males. The Missing = Failure approach was used for this analysis. Percentages were rounded-off.
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48	Week 48	HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a post baseline visit. HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative or missing at baseline to positive at a post baseline visit. The Missing = Failure approach was used for this analysis. Percentages were rounded-off.
Percentage of Participants With HBsAg Loss at Week 96	Week 96	HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a post baseline visit. HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative or missing at baseline to positive at a post baseline visit. The Missing = Failure approach was used for this analysis. Percentages were rounded-off.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm	Week 96	The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which was defined as 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. Percentages were rounded-off.
Change From Baseline in CD4 Cell Count at Week 48	Baseline, Week 48
Change From Baseline in CD4 Cell Count at Week 96	Baseline, Week 96
Change From Baseline in Percentage of CD4 Cells at Week 48	Baseline, Week 48
Change From Baseline in Percentage of CD4 Cells at Week 96	Baseline, Week 96
Percentage of Participants With Plasma HBV DNA < 29 IU/mL at Week 96	Week 96	This outcome measure was analyzed using a Missing = Failure approach. In this approach, all missing data were treated as HBV DNA ≥ 29 IU/mL. Percentages were rounded-off.
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48 by American Association for the Study of Liver Diseases (AASLD) Criteria	Week 48	ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given post baseline visit. The upper limit of the normal range (ULN) for ALT using the 2018 AASLD normal range was ≤ 25 U/L for females and ≤ 35 U/L for males. The Missing = Failure approach was used for this analysis. Percentages were rounded off.

Trial Locations

Locations (69)

Midway Immunology & Research; 🇺🇸 Fort Pierce, Florida, United States

Triple O Research Institute, P.A.; 🇺🇸 West Palm Beach, Florida, United States

Be Well Medical Center; 🇺🇸 Berkley, Michigan, United States

The Crofoot Research Center, INC (DBA: Gordon E. Crofoot MD PA); 🇺🇸 Houston, Texas, United States

Beijing Ditan Hospital Capital Medical University; 🇨🇳 Beijing, China

Beijing YouAn Hospital, Capital Medical University; 🇨🇳 Beijing, China

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences; 🇨🇳 Beijing, China

The First Hospital of Changsha; 🇨🇳 Changsha, China

Chengdu Public Health Clinical Center; 🇨🇳 Chengdu, China

Guangzhou Eighth people's Hospital; 🇨🇳 Guangzhou, China

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