The Effectiveness and Safety of TMF in the Treatment of Chronic Hepatitis B Patients With Normal ALT. (Promote)

A Prospective, Randomized, Blank Control, Multicenter Study to Evaluate the Efficacy and Safety of Alanine Aminotransferase（TMF）in the Treatment of Chronic Hepatitis B Patients With Normal Alanine Aminotransferase.

This is a multicenter, randomized, open, blank controlled trial ，in order to evaluate the effectiveness and safety of Amibufenamide（TMF） in the treatment of chronic hepatitis B virus infection patients with normal ALT .

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Hepatitis b; HBV Infection
• Intervention / Treatment: Drug: Tenofovir Amibufenamide（TMF）

Detailed Description

Although the indications for antiviral therapy for patients with chronic hepatitis B have been gradually expanded in different guidelines, antiviral treatment efficacy remains unclear among patients with alanine aminotransferase (ALT) < 1 upper limits of normal (ULN). This study aimed to evaluate the the effectiveness and safety of TMF for these patients.

Tenofovir amibufenamide (TMF; codename: HS-10234), another formulation of tenofovir, shared the same ProTide technology as tenofovir alafenamide, which can provide more efficient intracellular delivery than TDF.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing You'an Hospital, Capital Medical University
  • Dongyang, China
    • People's Hospital of Dongyang City
  • Fuyang, China
    • Fuyang Second People's Hospital
  • Hangzhou, China
    • The First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang Province
  • Lishui, China
    • LiShui People's Hospital of Zhejiang Province
  • Nanchang, China
    • The First Affiliated Hospital of NanChang University
  • Nanjin, China
    • Jiangsu Province Hospital
  • Shanghai, China
    • Shanghai East Hospital
  • Shanghai, China
    • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Suzhou, China
    • The Fifth People's Hospital of Suzhou
  • Wuxi, China
    • The Fifth People's Hospital of Wuxi
  • Hunan
    • Changsha, Hunan, China
      • The Second Xiangya Hospital, Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study screening.
2. Male and non-pregnant, non-lactating females, from 18 up to 65 years of age (based on the date of the screening visit). A negative serum pregnancy test at screening is required for female subjects of childbearing potential.
3. Documented evidence of chronic HBV infection (e.g. HBsAg positive for more than 6 months).
4. Normal alanine aminotransferase: serum HBV DNA >20 IU/mL and serum ALT level ≤ULN (40 IU/L) during screening.
5. Treatment-naive subjects will be eligible for enrollment.
6. Must be willing and able to comply with all study requirements.

Exclusion Criteria:

1. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.
2. Males and females of reproductive potential who are unwilling to use an "effective", protocol specified method(s) of contraception during the study.
3. Co-infection with HCV virus, HIV, HEV or HDV or combined with autoimmune liver disease, metabolism-related fatty liver disease, drug-induced liver injury;
4. Evidence of hepatocellular carcinoma (e.g. as evidenced by recent imaging).
5. Any history of, or current evidence of, clinical hepatic decompensation (e.g. ascites encephalopathy or variceal hemorrhage) or liver stiffness over 9kpa measured by TE.

6. Abnormal hematological and biochemical parameters, including:

   Hemoglobin < 10 g/dl Absolute neutrophil count < 0.75 × 10^9/L Platelets ≤ 50 × 10^9/L AST > 10 × ULN Total Bilirubin > 2.5 × ULN Albumin < 3.0 g/dL INR > 1.5 × ULN (unless stable on anticoagulant regimen) eGFR<50mL/min

7. Received solid organ or bone marrow transplant.
8. Malignancy within the 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc).
9. Currently receiving therapy with immunomodulators (e.g. corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion.
10. Complicated with uncontrollable cardiovascular and cerebrovascular diseases.
11. Subjects on prohibited concomitant medications. Subjects on prohibited medications, otherwise eligible, will need a wash out period of at least 30 days,Known hypersensitivity to study drugs, metabolites, or formulation excipients.
12. Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance.
13. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Blank control group; No antiviral therapy is given. If ALT>2 ULN (40 IU/L) for HBeAg-positive patients or > ULN for HBeAg-negative patients during the study period, blank control group can be switched to TMF treatment once a day, 25mg/ time orally until the end of the study.
Experimental: TMF treatment group; TMF 25mg QD, from baseline to 240 weeks	Drug: Tenofovir Amibufenamide（TMF）; TMF, 25mg QD, from baseline to 240 weeks; Other Names: HengMu

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA < 20 IU/mL	The primary efficacy endpoint was the proportion of patients with HBV DNA < 20 IU/mL at week 48	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation the change from Baseline in HBV DNA	Change from baseline in HBV DNA	Week 48，Week 96，Week 144，week 240
Evaluation the proportion of Patients Achieving Hepatitis B Surface Antigen (HBsAg) Loss	Proportion of patients achieving Hepatitis B surface antigen (HBsAg) loss	Week 48，Week 96，Week 144，Week 240
Evaluation the proportion of Patients Achieving HBsAg Seroconversion	Proportion of patients achieving HBsAg seroconversion	Week 48，Week 96, Week 144, Week 240
Evaluation the proportion of Patients Achieving HBeAg Seroconversion	Proportion of patients achieving HBeAg seroconversion	Week 48，Week 96，Week 144, Week 240
Evaluation the proportion of Patients Achieving HBeAg Loss	Proportion of patients Achieving HBeAg Loss	Week 48，Week 96，Week 144 ，Week 240
Evaluation the change from Baseline in HBsAg	Change from baseline in HBsAg	Week 48，Week 96，Week 144，Week 240
Evaluation the percentage of Participants with resistance	Percentage of participants with resistance	Week 48，Week 96，Week 144，Week 240
Evaluation the change from Baseline in liver fibrosis	Change from baseline in liver fibrosis	Week 48，Week 96，Week 144，Week 240
Evaluation the proportion of Patients with get hepatitis acute attack（ALT >5 ULN (40 IU/L)）	Proportion of patients with get hepatitis acute attack（ALT >5 ULN (40 IU/L)）	Week 48，Week 96，Week 144，Week 240
Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA < 20 IU/mL		Week 96，Week 144，Week 240
Evaluation the change from Baseline in Bone biomarker（β-CTX and P1NP）		Week 48，Week 96，Week 144，Week 240
Evaluation the change from Baseline in sCR		Week 48，Week 96，Week 144，Week 240
AE ,SAE		Week 48，Week 96，Week 144，Week 240
The proportion of subjects with liver-related events	Liver decompensation, acute-on-chronic liver failure, hepatocellular carcinoma, liver transplantation, all-cause mortality	Week 48，96，144，192，240

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Collaborators: Jiangsu Hansoh Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• Liu Z, Jin Q, Zhang Y, Gong G, Wu G, Yao L, Wen X, Gao Z, Huang Y, Yang D, Chen E, Mao Q, Lin S, Shang J, Gong H, Zhong L, Yin H, Wang F, Hu P, Xiao L, Li C, Wu Q, Sun C, Niu J, Hou J; TMF Study Group. Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B. Aliment Pharmacol Ther. 2021 Nov;54(9):1134-1149. doi: 10.1111/apt.16611. Epub 2021 Sep 29.
• Gui H, Shen Y, Tan L, Hu P, Qian F, Wu X, Qiu Y, Zheng S, Lv J, Shi Y, Li J, Jiang Y, Hu Z, Nie F, Huo Y, Qu L, Xie Q. Interim Analysis of 48-week Tenofovir Amibufenamide Treatment in Chronic Hepatitis B Patients with Normal Alanine Aminotransferase Levels: The PROMOTE Study. J Clin Transl Hepatol. 2025 Jul 28;13(7):568-577. doi: 10.14218/JCTH.2025.00162. Epub 2025 Jun 30.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2022
• Primary Completion (Actual): April 30, 2024
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: March 22, 2023
• First Submitted That Met QC Criteria: March 22, 2023
• First Posted (Actual): April 4, 2023

Study Record Updates

• Last Update Posted (Actual): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Treatment; Safety; Effectiveness; Normal Alanine Aminotransferase
• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Hepatitis; Pathological Conditions, Signs and Symptoms; Hepatitis B; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: PROMOTE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No