Clinical trial NCT02836236: Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate for Treatment of Hepatitis B e Antigen-Negative Hepatitis B (China)
Official title: A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD Versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QD for the Treatment of HBeAg-Negative, Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HBV
Chronic HBV Infection
Keywords: Hepatitis
Tenofovir
Viread
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-07-18
Enrollment: 155
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 compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in treatment-naive and treatment-experienced adults with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection in China.

Detailed description: This study GS-US-320-0108 is an international study planned to enroll participants in global countries, including China. However, due to the review timeline difference in China, full enrollment was reached in the main study (NCT01940341) before China was able to participate. Therefore, this registration only includes the China cohorts as they were not part of the main study analysis. Data for China cohorts were analyzed separately after the main study analysis was completed.

Eligibility criteria: Key Inclusion Criteria:

* Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Adult males and non-pregnant, non-lactating females
* Documented evidence of chronic HBV infection
* Hepatitis e antigen (HBeAg)-negative, chronic hepatitis B with all of the following:

  * HBeAg-negative and hepatitis B e antibody (HBeAb) positive at screening
  * Screening HBV DNA ≥ 2 x 10\^4 IU/mL
  * Screening serum alanine aminotransferase (ALT) level \> 60 U/L (males) or \> 38 U/L (females) and ≤ 10 x the upper limit of the normal range (ULN)
* Treatment-naive participants (defined as \< 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue), OR treatment-experienced participants (defined as participants meeting all entry criteria \[including HBV DNA and serum ALT criteria\] and with ≥ 12 weeks of previous treatment with any nucleoside or nucleotide analogue)
* Previous treatment with interferon (pegylated or non-pegylated) must have ended at least 6 months prior to the baseline visit.
* Adequate renal function
* Normal ECG

Key Exclusion Criteria:

* Females who are breastfeeding
* Males and females of reproductive potential who are unwilling to use an "effective", protocol-specified method(s) of contraception during the study
* Co-infection with hepatitis C virus, HIV, or hepatitis D virus
* Evidence of hepatocellular carcinoma
* Any history of, or current evidence of, clinical hepatic decompensation
* Abnormal hematological and biochemical parameters, including aspartate aminotransferase (AST) \> 10 x ULN
* Received solid organ or bone marrow transplant
* History of malignancy within the past 5 years, with the exception of specific cancers that are cured by surgical resection; individuals under evaluation for possible malignancy are not eligible
* Currently receiving therapy with immunomodulators (eg, corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion
* Individuals receiving ongoing therapy with drugs not to be used with tenofovir alafenamide or tenofovir disoproxil fumarate or individuals with a known hypersensitivity to study drugs, metabolites, or formulation excipients
* Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance
* 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 dosing requirements

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

Primary outcomes:
measure: Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
timeFrame: Baseline, Week 48
measure: Percent Change From Baseline in Spine BMD at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in Serum Creatinine at Week 48
timeFrame: Baseline, Week 48
Other outcomes:
measure: Percentage of Participants With Treatment-emergent Proteinuria by Urinalysis (Dipstick) Through Week 48
timeFrame: Up to 48 weeks
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Nanning
country: China
facility: The 1st Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Guiyang
country: China
facility: The Affiliated Hospital of Guiyang Medical College
state: Guiyang
city: Shijiazhuang
country: China
facility: The 3rd Hospital of Hebei Medical University
state: Hebei
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical college HuaZhong University of Science&Technology
state: Hubei
city: Nanjing
country: China
facility: Nanjing No. 2 Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: The sixth People's Hospital of Shenyang
state: Liaoning
city: Jinan
country: China
facility: Jinan Infectious Disease Hospital
state: Shandong
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Kunming
country: China
facility: No.1 Hospital Affiliated to Kunming Medical College
state: Yunnan
city: Beijing
country: China
facility: Beijing Ditan Hospital
city: Beijing
country: China
facility: No. 302 PLA Hospital
city: Beijing
country: China
facility: Peking University People's Hospital
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Youan Hospital, Capital Medical University
city: Changsha
country: China
facility: XiangYa Hospital Central South University
city: Changsha
country: China
facility: The 2nd Xiangya Hospital Central South University
city: Guangzhou
country: China
facility: Guangzhou No.8 People's Hospital
city: Guangzhou
country: China
facility: Nanfang Medical University, Nanfang Hospital
city: Haikou
country: China
facility: The People's Hospital of Hainan Province
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
city: Shanghai
country: China
facility: Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
city: Shanghai
country: China
facility: 85 Hospital of People's Liberation Army
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Hou J, Ning Q, Duan Z, Chen Y, Xie Q, Wang FS, Zhang L, Wu S, Tang H, Li J, Lin F, Yang Y, Gong G, Flaherty JF, Gaggar A, Mo S, Cheng C, Camus G, Chen C, Huang Y, Jia J, Zhang M; GS-US-320-0110 and GS-US-320-0108 China Investigators. 3-year Treatment of Tenofovir Alafenamide vs. Tenofovir Disoproxil Fumarate for Chronic HBV Infection in China. J Clin Transl Hepatol. 2021 Jun 28;9(3):324-334. doi: 10.14218/JCTH.2020.00145. Epub 2021 Apr 28.
citation: Hou J, Ning Q, Duan Z, Chen Y, Xie Q, Zhang L, Wu S, Tang H, Li J, Lin F, Yang Y, Gong G, Luo Y, Xie S, Wang H, Mateo R, Yazdi T, Abramov F, Yee LJ, Flaherty J, Chen C, Huang Y, Zhang M, Jia J. Five-year Treatment with Tenofovir Alafenamide Achieves High Rates of Viral Suppression, Alanine Aminotransferase Normalization, and Favorable Bone and Renal Safety in Chinese Chronic Hepatitis B Patients. J Clin Transl Hepatol. 2024 May 28;12(5):469-480. doi: 10.14218/JCTH.2023.00417. Epub 2024 Apr 15.