Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B

Zhihong Liu, Qinglong Jin, Yuexin Zhang, Guozhong Gong, Guicheng Wu, Lvfeng Yao, Xiaofeng Wen, Zhiliang Gao, Yan Huang, Daokun Yang, Enqiang Chen, Qing Mao, Shide Lin, Jia Shang, Huanyu Gong, Lihua Zhong, Huafa Yin, Fengmei Wang, Peng Hu, Ling Xiao, Chuan Li, Qiong Wu, Chang'an Sun, Junqi Niu, Jinlin Hou, TMF Study Group, Zhihong Liu, Qinglong Jin, Yuexin Zhang, Guozhong Gong, Guicheng Wu, Lvfeng Yao, Xiaofeng Wen, Zhiliang Gao, Yan Huang, Daokun Yang, Enqiang Chen, Qing Mao, Shide Lin, Jia Shang, Huanyu Gong, Lihua Zhong, Huafa Yin, Fengmei Wang, Peng Hu, Ling Xiao, Chuan Li, Qiong Wu, Chang'an Sun, Junqi Niu, Jinlin Hou, TMF Study Group

Abstract

Background: Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF).

Aim: To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB).

Methods: We performed a randomised, double-blind, non-inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities.

Results: We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non-inferiority criterion was met in all analysis sets. In the HBeAg-positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAg-negative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip (P < 0.001) and spine (P < 0.001), and a smaller increase in serum creatinine at week 48 (P < 0.05). Other safety results were similar between groups.

Conclusion: TMF was non-inferior to TDF in terms of anti-HBV efficacy and showed better bone and renal safety. (NCT03903796).

© 2021 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Trial profile. This flowchart presented the screening, randomisation and study drug exposure in our study
FIGURE 2
FIGURE 2
The non‐inferiority of virological suppression in all analysis set. The non‐inferiority of virological suppression, which is defined as HBV DNA

FIGURE 3

Changes in bone mineral density.…

FIGURE 3

Changes in bone mineral density. A, Mean percentage change in hip bone mineral…

FIGURE 3
Changes in bone mineral density. A, Mean percentage change in hip bone mineral density at weeks 24 and 48 of treatment. Bars are 95% CI. B, Mean percentage change in spine bone mineral density at weeks 24 and 48 of treatment. Bars are 95% CI

FIGURE 4

Change in serum creatinine, by…

FIGURE 4

Change in serum creatinine, by treatment group. Mean change from baseline in serum…

FIGURE 4
Change in serum creatinine, by treatment group. Mean change from baseline in serum creatinine (µmol/L) by study visit.
FIGURE 3
FIGURE 3
Changes in bone mineral density. A, Mean percentage change in hip bone mineral density at weeks 24 and 48 of treatment. Bars are 95% CI. B, Mean percentage change in spine bone mineral density at weeks 24 and 48 of treatment. Bars are 95% CI
FIGURE 4
FIGURE 4
Change in serum creatinine, by treatment group. Mean change from baseline in serum creatinine (µmol/L) by study visit.

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