Clinical trial NCT03547908: 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
Official title: A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Fixed Dose Combination of Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment Naïve, HIV-1 and Hepatitis B Co-Infected Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1/HBV Co-Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2018-06-06
Enrollment: 244
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 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.


Eligibility criteria: Key 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.

Primary outcomes:
measure: 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)
timeFrame: Week 48
measure: 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)
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 96
measure: Change From Baseline in CD4 Cell Count at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in CD4 Cell Count at Week 96
timeFrame: Baseline, Week 96
measure: Change From Baseline in Percentage of CD4 Cells at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in Percentage of CD4 Cells at Week 96
timeFrame: Baseline, Week 96
measure: Percentage of Participants With Plasma HBV DNA < 29 IU/mL at Week 96
timeFrame: Week 96
measure: Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48 by American Association for the Study of Liver Diseases (AASLD) Criteria
timeFrame: Week 48
measure: Percentage of Participants With ALT Normalization at Week 96
timeFrame: Week 96
measure: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HBsAg Loss at Week 96
timeFrame: Week 96
Other outcomes:
Locations:
city: Fort Pierce
country: United States
facility: Midway Immunology & Research
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A.
state: Florida
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Houston
country: United States
facility: The Crofoot Research Center, INC (DBA: Gordon E. Crofoot MD PA)
state: Texas
city: Beijing
country: China
facility: Beijing Ditan Hospital Capital Medical University
city: Beijing
country: China
facility: Beijing YouAn Hospital, Capital Medical University
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
city: Changsha
country: China
facility: The First Hospital of Changsha
city: Chengdu
country: China
facility: Chengdu Public Health Clinical Center
city: Guangzhou
country: China
facility: Guangzhou Eighth people's Hospital
city: Hangzhou
country: China
facility: 1st Affiliated Hospital of Zhejiang University
city: Nanjing
country: China
facility: The Second Hospital of Nanjing
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
city: Shenzhen
country: China
facility: Third People's Hospital Of Shenzhen
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dominicano de Estudios Virologicos (IDEV)
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
city: Athens
country: Greece
facility: Evaggelismos General Hospital of Athens
city: Athens
country: Greece
facility: Korgialenio-Benakio Greek Red Cross General Hospital
city: Athens
country: Greece
facility: Laiko General Hospital
city: Thessaloniki
country: Greece
facility: AHEPA University Hospital of Thessaloniki
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Elizabeth Hospital (QEH)
city: Kowloon
country: Hong Kong
facility: Princess Margaret Hospital
city: Aichi
country: Japan
facility: National Hospital Organization Nagoya Medical Center
city: Okinawa
country: Japan
facility: University of the Ryukyus Hospital
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Tokyo
country: Japan
facility: The Jikei University Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine
city: Yokohama
country: Japan
facility: Yokohama City University Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
city: Kota Bahru
country: Malaysia
facility: Hospital Raja Perempuan Zainab II
city: Kota Kinabalu
country: Malaysia
facility: Queen Elizabeth Hospital
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Terengganu
country: Malaysia
facility: Hospital Sultanah Nur Zahirah
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
city: Pulau Pinang
country: Malaysia
facility: Hospital Pulau Pinang
city: Sungai Buloh
country: Malaysia
facility: Sungai Buloh Hospital
city: San Juan
country: Puerto Rico
facility: Hope Clinical Research
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Cartagena
country: Spain
facility: Hospital General Universitario Santa Lucia
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital de Canarias
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Vigo
country: Spain
facility: CHUVI - Hospital Universitario Alvaro Cunqueiro
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei City Hospital Linsen, Chinese Medicine and Kunming Branch
city: Taoyuan City
country: Taiwan
facility: Ministry of Health and Welfare Taoyuan General Hospital
city: Bangkok
country: Thailand
facility: Thai Red Cross AIDS Research Centre (HIV-NAT)
city: Bangkok
country: Thailand
facility: Faculty of Medicine Ramathibodi Hospital, Mahidol University
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Faculty of Medicine, Chiang Mai University
city: Chiang Rai
country: Thailand
facility: Chiang Rai Reginal Hospital
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital
city: Nonthaburi
country: Thailand
facility: Bamrasnaradura Infectious Diseases Institute
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Istanbul
country: Turkey
facility: Marmara University Pendik Training and Research Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Avihingsanon, A. 2022. Week 48 results of a Phase 3 randomized controlled trial of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir + emtricitabine/tenofovir Disoproxil Fumarate (DTG+F/TDF) as initial treatment in HIV/HBV-coinfected adults (ALLIANCE). AIDS, 29 July 29-2 August 2022, Montréal, Québec, Canada.
citation: Avihingsanon A, Lu H, Leong CL, Hung CC, Koenig E, Kiertiburanakul S, Lee MP, Supparatpinyo K, Zhang F, Rahman S, D'Antoni ML, Wang H, Hindman JT, Martin H, Baeten JM, Li T; ALLIANCE Study Team. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 and hepatitis B coinfection (ALLIANCE): a double-blind, multicentre, randomised controlled, phase 3 non-inferiority trial. Lancet HIV. 2023 Oct;10(10):e640-e652. doi: 10.1016/S2352-3018(23)00151-0. Epub 2023 Jul 23.
citation: Brief Report: HIV-1 Resistance Analysis of Participants With HIV-1 and Hepatitis B Initiating Therapy With Bictegravir/Emtricitabine/Tenofovir Alafenamide or Dolutegravir Plus Emtricitabine/Tenofovir Disoproxil Fumarate: A Subanalysis of ALLIANCE Data: Erratum. J Acquir Immune Defic Syndr. 2024 Oct 1;97(2):202. doi: 10.1097/QAI.0000000000003494. No abstract available.
citation: Avihingsanon A, Lu H, Leong CL, Hung C-C, Kiertiburanakul S, Lee M-P, Supparatpinyo K, Zhang F, Hindman JT, Wang H, Liu H and Li T. Factors Associated with HBV Response to B/F/TAF vs. DTG + F/TDF at W96 in People with HIV-1 and HBV. CROI, March 3-6, 2024.
citation: Avihingsanon A, Lu H, Leong C, Hung C, Koenig E, Kiertiburanakul S, et al. Week-96 results of ALLIANCE, a Phase 3, randomized, double-blind study comparing bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+F/TDF) in treatment-naive people with both HIV-1 and hepatitis B. 12th International AIDS Society Conference on HIV Science 2023, 23-26 July.
citation: D'Antoni M, Andreatta K, Cox S, Chang S, Hindman J, Martin H, et al. HIV-1 resistance analysis of treatment-naive participants with HIV-1 and hepatitis B coinfection receiving bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir + emtricitabine/tenofovir disoproxil fumarate. European Meeting on HIV and Hepatitis 2023, 7-9 June, Rome, Italy.
citation: Avihingsanon A, Leong C, Hung C, Koenig E, Lee M, Supparatpinyo K, et al. Predictors of hepatitis B treatment response in people with HIV-1/HBV coinfection. Conference on Retroviruses and Opportunistic Infections (CROI) 2023, 19-22 February; Seattle, Washington.
citation: Avihingsanon A, Lu H, Leong C, Hung C, Koenig E, Kiertiburanakul S, et al. Week 48 results of a Phase 3 randomized controlled trial of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+F/TDF) as initial treatment in HIV/HBV coinfected adults (ALLIANCE). AIDS (Conference) 2022, 29 July 2 August; Montréal, Québec, Canada.