Clinical trial NCT01300234: Efficacy and Safety of Tenofovir Disoproxil Fumarate (TDF) 300mg in Chinese Subjects With Chronic Hepatitis B (CHB)
Official title: A Multi-centre, Double Blind, Double Dummy, Randomised, Controlled Study to Evaluate the Efficacy and Safety of TDF 300mg Once Daily (QD) Versus Adefovir Dipivoxil (ADV) 10mg QD in Chinese Subjects With CHB
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis B
Keywords: tenofovir disoproxil fumarate
chronic hepatitis B
adefovir dipivoxil
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-02-21
Enrollment: 512
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-centre, double blind, double dummy, randomised, controlled study to evaluate the efficacy and safety of TDF 300mg QD versus ADV 10mg QD in Chinese subjects with CHB. This study is designed to demonstrate the superiority of TDF 300mg QD over ADV 10mg QD in treating Chinese subjects with CHB (hepatitis B e antigen \[HBeAg\] positive subjects and HBeAg negative subjects). It will also provide long-term efficacy and safety data (up to 240 weeks) for TDF 300 mg administered once daily.

Detailed description: This is a multi-centre, double-blind, double-dummy, randomised, controlled study to evaluate the efficacy and safety of TDF 300mg QD versus ADV 10mg QD in Chinese subjects with CHB. Four hundred and ninety-four subjects with CHB (200 HBeAg positive subjects and 294 HBeAg negative subjects) will be randomised (1:1ratio) to either TDF 300mg QD or ADV 10mg QD treatment arms. The primary endpoint is the proportion of subjects with blood hepatitis B virus (HBV) deoxyribonucleic acid (DNA) \<400copies/mL (Roche COBAS Taqman HBV test) at Week 48 in HBeAg positive subjects with CHB and HBeAg negative subjects with CHB. This is a two-part study. The first treatment period (baseline to Week 48) will investigate the effects of TDF and ADV on safety and efficacy endpoints; dosing will be double-blind. This period will be followed by 192 weeks in which all subjects will receive open-label TDF (Week 49 to Week 240). Subjects will undergo regular safety and efficacy assessments every 4 weeks for the first 12 weeks followed by every 12 weeks for a total of up to 5 years.

Eligibility criteria: Inclusion Criteria:

* HBeAg positive/negative CHB with blood HBVDNA≥10\^5 copies/mL and elevated ALT
* Nucleoside and nucleotide naïve CHB subjects. Previous lamivudine treatment is allowed in less than 10% of the total study population

Exclusion Criteria:

* subjects with hepatocellular carcinoma (HCC) potential or decompensated liver disease
* subjects with acute liver disease due to other causes
* subjects with medication history of immunosuppressive therapy, immunomodulatory therapy, systemic cytotoxic agents, chronic antiviral agents including Chinese herbal medicines known to have activity against HBV (e.g., lamivudine, hepatitis B immunoglobulin (HBIg)) within the previous 6 months prior to randomisation into this study

Primary outcomes:
measure: Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <400 Copies/Milliliter (mL) at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Participants With HBV DNA <400 Copies/mL at Weeks 96, 144, 192, and 240
timeFrame: Weeks 96, 144, 192, and 240
measure: Change From Baseline of Log 10 Copies/mL HBV DNA at Weeks 48, 96, 144, 192 and 240
timeFrame: Baseline, Weeks 48, 96, 144, 192 and 240
measure: Number of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48, 96, 144, 192 and 240 in Participants Who Had Abnormal ALT at Baseline
timeFrame: Baseline; Weeks 48, 96, 144, 192 and 240
measure: Number of Participants With Histological Improvement at Weeks 48 and 240 Who Had a Baseline Knodell Necroinflammatory Score (KNS) >=2.
timeFrame: Baseline; Week 48 and Week 240
measure: Number of HBeAg-positive Participants Achieving HBeAg Loss and HBeAg Seroconversion at Weeks 24, 48, 96, 144, 192 and 240.
timeFrame: Weeks 24, 48, 96, 144, 192 and 240
measure: Number of HBeAg-positive Participants Achieving Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Weeks 24, 48, 96, 144, 192 and 240
timeFrame: Weeks 24, 48, 96, 144, 192 and 240
measure: Number of HBeAg-negative Participants Achieving HBsAg Loss and HBsAg Seroconversion at Weeks 24, 48, 96, 144, 192, 240
timeFrame: Weeks 24, 48, 96, 144, 192 and 240
measure: Number of Participants Achieving Durable HBsAg Loss From Weeks 24 to Week 48
timeFrame: Week 24 to Week 48
measure: Number of Participants Achieving Durable HBsAg Loss From Weeks 96 to Week 240
timeFrame: Week 96 to Week 240
measure: Number of Participants With Virological Breakthrough at Weeks 48, 96, 144, 192 and 240
timeFrame: Weeks 48, 96, 144, 192 and 240
measure: Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (AE)
timeFrame: Up to Week 240 treatment period and 24 weeks follow-up visit off treatment
measure: Number of Participants With the Indicated Grade 3 and Grade 4 Treatment-emergent (TE) Laboratory Abnormalities (LAs)
timeFrame: Up to Week 240
measure: Number of Participants With the Indicated Treatment-emergent Laboratory Abnormalities for Serum Creatinine and Serum Phosphorus
timeFrame: Up to Week 240
measure: Number of Participants in the Indicated Category for Renal Laboratory Abnormalities
timeFrame: Up to Week 240
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Wuhan
country: China
facility: GSK Investigational Site
state: Hubei
city: Changsha
country: China
facility: GSK Investigational Site
state: Hunan
city: Nanjing
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Nanjing
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Changchun
country: China
facility: GSK Investigational Site
state: Jilin
city: Chengdu
country: China
facility: GSK Investigational Site
state: Sichuan
city: Hangzhou
country: China
facility: GSK Investigational Site
state: Zhejiang
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Chongqing
country: China
facility: GSK Investigational Site
city: Fuzhou
country: China
facility: GSK Investigational Site
city: Jinan
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Liang X, Gao Z, Xie Q, Zhang J, Sheng J, Cheng J, Chen C, Mao Q, Zhao W, Ren H, Tan D, Niu J, Chen S, Pan C, Tang H, Wang H, Mao Y, Jia J, Ning Q, Xu M, Wu S, Li J, Zhang X, Zhang W, Xiong C, Hou J. Long-term efficacy and safety of tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B: 5-year results. Hepatol Int. 2019 May;13(3):260-269. doi: 10.1007/s12072-019-09943-6. Epub 2019 Apr 11.
citation: Hou JL, Gao ZL, Xie Q, Zhang JM, Sheng JF, Cheng J, Chen CW, Mao Q, Zhao W, Ren H, Tan DM, Niu JQ, Chen SJ, Pan C, Tang H, Wang H, Mao YM, Jia JD, Ning Q, Xu M, Wu SM, Li J, Zhang XX, Ji Y, Dong J, Li J. Tenofovir disoproxil fumarate vs adefovir dipivoxil in Chinese patients with chronic hepatitis B after 48 weeks: a randomized controlled trial. J Viral Hepat. 2015 Feb;22(2):85-93. doi: 10.1111/jvh.12313. Epub 2014 Sep 22.