HIV-1/HBV Co-Infection Clinical Trial
— AllianceOfficial 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
| Verified date | March 2024 |
| Source | Gilead Sciences |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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 HIV and hepatitis B virus (HBV) treatment naive, HIV-1 and HBV co-infected adults.
| Status | Completed |
| Enrollment | 244 |
| Est. completion date | March 7, 2024 |
| Est. primary completion date | February 25, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Key Inclusion Criteria: - HIV-1 co-infection: - Must be HIV antiretroviral treatment naive with plasma HIV-1 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 HBV treatment naive (defined as < 12 weeks of oral antiviral treatment) - Screening HBV DNA = 2000 IU/mL - Hepatic transaminases (aspartate aminotransferase (AST) and 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. |
| Country | Name | City | State |
|---|---|---|---|
| China | 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 | 1st Affiliated Hospital of Zhejiang University | Hangzhou | |
| China | The Second Hospital of Nanjing | Nanjing | |
| China | Shanghai Public Health Clinical Center | Shanghai | |
| China | Third People's Hospital Of Shenzhen | Shenzhen | |
| Dominican Republic | Instituto Dominicano de Estudios Virologicos (IDEV) | Santo Domingo | |
| France | Hôpital de la Croix Rousse | Lyon | |
| Greece | Evaggelismos General Hospital of Athens | Athens | |
| Greece | Korgialenio-Benakio Greek Red Cross General Hospital | Athens | |
| Greece | Laiko General Hospital | Athens | |
| Greece | AHEPA University Hospital of Thessaloniki | Thessaloniki | |
| Hong Kong | Prince of Wales Hospital | Hong Kong | |
| Hong Kong | Queen Elizabeth Hospital (QEH) | Hong Kong | |
| Hong Kong | Princess Margaret Hospital | Kowloon | |
| Japan | National Hospital Organization Nagoya Medical Center | Aichi | |
| Japan | University of the Ryukyus Hospital | Okinawa | |
| Japan | National Hospital Organization Osaka National Hospital | Osaka | |
| Japan | Osaka City General Hospital | Osaka | |
| Japan | Center Hospital of the National Center for Global Health and Medicine | Tokyo | |
| Japan | Juntendo University Hospital | Tokyo | |
| Japan | The Jikei University Hospital | Tokyo | |
| Japan | Yokohama City University Hospital | Yokohama | |
| Korea, Republic of | Pusan National University Hospital | Busan | |
| Korea, Republic of | The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | |
| Malaysia | Hospital Raja Permaisuri Bainun | Ipoh | |
| Malaysia | Hospital Raja Perempuan Zainab II | Kota Bahru | |
| Malaysia | Queen Elizabeth Hospital | Kota Kinabalu | |
| Malaysia | Hospital Kuala Lumpur | Kuala Lumpur | |
| Malaysia | University Malaya Medical Centre | Kuala Lumpur | |
| Malaysia | Hospital Sultanah Nur Zahirah | Kuala Terengganu | |
| Malaysia | Sarawak General Hospital | Kuching | |
| Malaysia | Hospital Pulau Pinang | Pulau Pinang | |
| Malaysia | Sungai Buloh Hospital | Sungai Buloh | |
| Puerto Rico | Hope Clinical Research | San Juan | |
| Spain | Hospital Clinic de Barcelona | Barcelona | |
| Spain | Hospital General Universitario Santa Lucia | Cartagena | |
| Spain | Fundacion Jimenez Diaz | Madrid | |
| Spain | Hospital Universitario 12 de Octubre | Madrid | |
| Spain | Hospital Universitario La Paz | Madrid | |
| Spain | Hospital de Canarias | Santa Cruz de Tenerife | |
| Spain | Hospital General Universitario de Valencia | Valencia | |
| Spain | CHUVI - Hospital Universitario Alvaro Cunqueiro | Vigo | |
| Taiwan | Kaohsiung Medical University Chung-Ho Memorial Hospital | Kaohsiung | |
| Taiwan | Kaohsiung Veterans General Hospital | Kaohsiung | |
| Taiwan | Far Eastern Memorial Hospital | New Taipei City | |
| Taiwan | Taichung Veterans General Hospital | Taichung | |
| Taiwan | National Cheng Kung University Hospital | Tainan | |
| Taiwan | National Taiwan University Hospital | Taipei | |
| Taiwan | Taipei City Hospital Linsen, Chinese Medicine and Kunming Branch | Taipei | |
| Taiwan | Taipei Veterans General Hospital | Taipei City | |
| Taiwan | Ministry of Health and Welfare Taoyuan General Hospital | Taoyuan City | |
| Thailand | Faculty of Medicine Ramathibodi Hospital, Mahidol University | Bangkok | |
| Thailand | Siriraj Hospital | Bangkok | |
| Thailand | Thai Red Cross AIDS Research Centre (HIV-NAT) | Bangkok | |
| Thailand | Faculty of Medicine, Chiang Mai University | Chiang Mai | |
| Thailand | Chiang Rai Reginal Hospital | Chiang Rai | |
| Thailand | Srinagarind Hospital | Khon Kaen | |
| Thailand | Bamrasnaradura Infectious Diseases Institute | Nonthaburi | |
| Turkey | Istanbul University Cerrahpasa Medical Faculty | Istanbul | |
| Turkey | Marmara University Pendik Training and Research Hospital | Istanbul | |
| United States | Be Well Medical Center | Berkley | Michigan |
| United States | Midway Immunology & Research | Fort Pierce | Florida |
| United States | The Crofoot Research Center, INC (DBA: Gordon E. Crofoot MD PA) | Houston | Texas |
| United States | Triple O Research Institute, P.A. | West Palm Beach | Florida |
| Lead Sponsor | Collaborator |
|---|---|
| Gilead Sciences |
United States, China, Dominican Republic, France, Greece, Hong Kong, Japan, Korea, Republic of, Malaysia, Puerto Rico, Spain, Taiwan, Thailand, Turkey,
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. — View 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.
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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) | 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. | Week 48 | |
| Primary | 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) | This outcome measure was analyzed using a Missing = Failure approach. In this approach, all missing on-treatment data were treated as HBV DNA = 29 IU/mL. | Week 48 | |
| Secondary | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm | Week 96 | ||
| Secondary | Change From Baseline in CD4 Cell Count at Week 48 | Baseline; Week 48 | ||
| Secondary | Change From Baseline in CD4 Cell Count at Week 96 | Baseline; Week 96 | ||
| Secondary | Change From Baseline in CD4 Percentage at Week 48 | Baseline; Week 48 | ||
| Secondary | Change From Baseline in CD4 Percentage at Week 96 | Baseline; Week 96 | ||
| Secondary | Percentage of Participants With Plasma HBV DNA < 29 IU/mL at Week 96 | Week 96 | ||
| Secondary | Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48 by American Association for the Study of Liver Diseases (AASLD) Criteria | 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. | Week 48 | |
| Secondary | Percentage of Participants With ALT Normalization at Week 96 | Week 96 | ||
| Secondary | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at 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. | Week 48 | |
| Secondary | Percentage of Participants With HBsAg Loss at Week 96 | Week 96 |