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

Chronic Hepatitis b Clinical Trial

— Promote  

Official title:

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05797714
• Other study ID #: Promote
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 8, 2022
• Est. completion date: April 15, 2026

Study information

• Verified date: March 2024
• Source: Ruijin Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 .

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: April 15, 2026
• Est. primary completion date: June 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis b
• HBV Infection
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Tenofovir Amibufenamide(TMF)
TMF, 25mg QD, from baseline to 144 weeks

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Ruijin Hospital	Jiangsu Hansoh Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Evaluation the change from Baseline in HBV DNA	Change from baseline in HBV DNA	Week 48,Week 96,Week 144
Secondary	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
Secondary	Evaluation the proportion of Patients Achieving HBsAg Seroconversion	Proportion of patients achieving HBsAg seroconversion	Week 48,Week 96,Week 144
Secondary	Evaluation the proportion of Patients Achieving HBeAg Seroconversion	Proportion of patients achieving HBeAg seroconversion	Week 48,Week 96,Week 144
Secondary	Evaluation the proportion of Patients Achieving HBeAg Loss	Proportion of patients Achieving HBeAg Loss	Week 48,Week 96,Week 144
Secondary	Evaluation the change from Baseline in HBsAg	Change from baseline in HBsAg	Week 48,Week 96,Week 144
Secondary	Evaluation the percentage of Participants with resistance	Percentage of participants with resistance	Week 48,Week 96,Week 144
Secondary	Evaluation the change from Baseline in liver fibrosis	Change from baseline in liver fibrosis	Week 48,Week 96,Week 144
Secondary	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
Secondary	Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA < 20 IU/mL		Week 96,Week 144
Secondary	Evaluation the change from Baseline in Bone biomarker(ß-CTX and P1NP)		Week 48,Week 96,Week 144
Secondary	Evaluation the change from Baseline in sCR		Week 48,Week 96,Week 144
Secondary	AE ,SAE		Week 48,Week 96,Week 144