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
- Conditions
- HIV-1/HBV Co-Infection
- Interventions
- Drug: B/F/TAFDrug: Placebo to match DTGDrug: Placebo to match F/TDFDrug: 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 244
-
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
- 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 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.
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.
Trial Locations
- Locations (69)
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Taipei Veterans General Hospital
🇨🇳Taipei City, Taiwan
CHUVI - Hospital Universitario Alvaro Cunqueiro
🇪🇸Vigo, Spain
Hospital General Universitario Santa Lucia
🇪🇸Cartagena, Spain
Hope Clinical Research
🇵🇷San Juan, Puerto Rico
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Taipei City Hospital Linsen, Chinese Medicine and Kunming Branch
🇨🇳Taipei, Taiwan
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital de Canarias
🇪🇸Santa Cruz de Tenerife, Spain
Far Eastern Memorial Hospital
🇨🇳New Taipei City, Taiwan
Srinagarind Hospital
🇹🇭Khon Kaen, Thailand
Faculty of Medicine Ramathibodi Hospital, Mahidol University
🇹🇭Bangkok, Thailand
Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Chiang Rai Reginal Hospital
🇹🇭Chiang Rai, Thailand
Triple O Research Institute, P.A.
🇺🇸West Palm Beach, Florida, United States
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
Beijing Ditan Hospital Capital Medical University
🇨🇳Beijing, China
Beijing YouAn Hospital, Capital Medical University
🇨🇳Beijing, China
The First Hospital of Changsha
🇨🇳Changsha, China
Chengdu Public Health Clinical Center
🇨🇳Chengdu, China
Shanghai Public Health Clinical Center
🇨🇳Shanghai, China
Instituto Dominicano de Estudios Virologicos (IDEV)
🇩🇴Santo Domingo, Dominican Republic
Third People's Hospital Of Shenzhen
🇨🇳Shenzhen, China
Hôpital de la Croix Rousse
🇫🇷Lyon, France
Evaggelismos General Hospital of Athens
🇬🇷Athens, Greece
Korgialenio-Benakio Greek Red Cross General Hospital
🇬🇷Athens, Greece
AHEPA University Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Prince of Wales Hospital
🇭🇰Hong Kong, Hong Kong
Osaka City General Hospital
🇯🇵Osaka, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
Center Hospital of the National Center for Global Health and Medicine
🇯🇵Tokyo, Japan
Hospital Raja Perempuan Zainab II
🇲🇾Kota Bahru, Malaysia
Hospital Kuala Lumpur
🇲🇾Kuala Lumpur, Malaysia
Sarawak General Hospital
🇲🇾Kuching, Malaysia
Hospital Pulau Pinang
🇲🇾Pulau Pinang, Malaysia
Sungai Buloh Hospital
🇲🇾Sungai Buloh, Malaysia
Guangzhou Eighth people's Hospital
🇨🇳Guangzhou, China
1st Affiliated Hospital of Zhejiang University
🇨🇳Hangzhou, China
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
🇨🇳Beijing, China
The Crofoot Research Center, INC (DBA: Gordon E. Crofoot MD PA)
🇺🇸Houston, Texas, United States
National Hospital Organization Nagoya Medical Center
🇯🇵Aichi, Japan
University of the Ryukyus Hospital
🇯🇵Okinawa, Japan
Yokohama City University Hospital
🇯🇵Yokohama, Japan
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Laiko General Hospital
🇬🇷Athens, Greece
The Jikei University Hospital
🇯🇵Tokyo, Japan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Ministry of Health and Welfare Taoyuan General Hospital
🇨🇳Taoyuan City, Taiwan
Thai Red Cross AIDS Research Centre (HIV-NAT)
🇹🇭Bangkok, Thailand
Hospital Sultanah Nur Zahirah
🇲🇾Kuala Terengganu, Malaysia
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Hospital Raja Permaisuri Bainun
🇲🇾Ipoh, Malaysia
Queen Elizabeth Hospital
🇲🇾Kota Kinabalu, Malaysia
Siriraj Hospital
🇹🇭Bangkok, Thailand
Bamrasnaradura Infectious Diseases Institute
🇹🇭Nonthaburi, Thailand
Istanbul University Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
Marmara University Pendik Training and Research Hospital
🇹🇷Istanbul, Turkey
Midway Immunology & Research
🇺🇸Fort Pierce, Florida, United States
National Hospital Organization Osaka National Hospital
🇯🇵Osaka, Japan
Kaohsiung Veterans General Hospital
🇨🇳Kaohsiung, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Faculty of Medicine, Chiang Mai University
🇹🇭Chiang Mai, Thailand
The Second Hospital of Nanjing
🇨🇳Nanjing, China
Princess Margaret Hospital
🇭🇰Kowloon, Hong Kong
Queen Elizabeth Hospital (QEH)
🇭🇰Hong Kong, Hong Kong