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

Sponsor

Ruijin Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05797714

Collaborator

Jiangsu Hansoh Pharmaceutical Co., Ltd. (Industry)

200

Enrollment

Locations

Arms

21.7

Anticipated Duration (Months)

16.7

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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 at week 48.

Condition or Disease	Intervention/Treatment	Phase
HBV Infection Chronic Hepatitis b	Drug: Tenofovir Amibufenamide（TMF）	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The subjects were randomly divided into two groups. One group received TMF treatment for 48 weeks. Aonther group received no antiviral therapy and served as a blank control.The subjects were randomly divided into two groups. One group received TMF treatment for 48 weeks. Aonther group received no antiviral therapy and served as a blank control.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Actual Study Start Date :

Jun 23, 2022

Anticipated Primary Completion Date :

Apr 15, 2024

Anticipated Study Completion Date :

Apr 15, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TMF treatment group TMF 25mg QD, from baseline to 48 weeks	Drug: Tenofovir Amibufenamide（TMF） TMF, 25mg QD, from baseline to 48 weeks Other Names: HengMu
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.

Arm

Intervention/Treatment

Experimental: TMF treatment group

TMF 25mg QD, from baseline to 48 weeks

Drug: Tenofovir Amibufenamide（TMF）

TMF, 25mg QD, from baseline to 48 weeks

Other Names:

HengMu

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Evaluation the change from Baseline in HBV DNA [Week 48]
Change from baseline in HBV DNA
Evaluation the proportion of Patients Achieving Hepatitis B Surface Antigen (HBsAg) Loss [Week 48]
Proportion of patients achieving Hepatitis B surface antigen (HBsAg) loss
Evaluation the proportion of Patients Achieving HBsAg Seroconversion [Week 48]
Proportion of patients achieving HBsAg seroconversion
Evaluation the proportion of Patients Achieving HBeAg Seroconversion [Week 48]
Proportion of patients achieving HBeAg seroconversion
Evaluation the proportion of Patients Achieving HBeAg Loss [Week 48]
Proportion of patients Achieving HBeAg Loss
Evaluation the change from Baseline in HBsAg [Week 48]
Change from baseline in HBsAg
Evaluation the percentage of Participants with resistance [Week 48]
Percentage of participants with resistance
Evaluation the change from Baseline in liver fibrosis [Week 48]
Change from baseline in liver fibrosis
Evaluation the proportion of Patients with get hepatitis acute attack（ALT >5 ULN (40 IU/L)） [Week 48]
Proportion of patients with get hepatitis acute attack（ALT >5 ULN (40 IU/L)）

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study screening.
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.
Documented evidence of chronic HBV infection (e.g. HBsAg positive for more than 6 months).
Normal alanine aminotransferase: serum HBV DNA >20 IU/mL and serum ALT level ≤ULN (40 IU/L) during screening.
Treatment-naive subjects will be eligible for enrollment.
Must be willing and able to comply with all study requirements.

Exclusion Criteria:

Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.
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 HCV virus, HIV, HEV or HDV or combined with autoimmune liver disease, metabolism-related fatty liver disease, drug-induced liver injury;
Evidence of hepatocellular carcinoma (e.g. as evidenced by recent imaging).
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.
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

Received solid organ or bone marrow transplant.
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).
Currently receiving therapy with immunomodulators (e.g. corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion.
Complicated with uncontrollable cardiovascular and cerebrovascular diseases.
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.
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 subject unsuitable for the study or unable to comply with dosing requirements.

Contacts and Locations

Locations

	Site	City	Country
1	Beijing You'An Hospital, Capital Medical University	Beijing	China
2	People's Hospital of Dongyang City	Dongyang	China
3	Fuyang Second People's Hospital	Fuyang	China
4	The First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang Province	Hangzhou	China
5	LiShui People's Hospital of Zhejiang Province	LiShui	China
6	The First Affiliated Hospital of Nanchang University	Nanchang	China
7	Jiangsu Province Hospital	Nanjin	China
8	Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.	Shanghai	China
9	Shanghai East Hospital	Shanghai	China
10	Xiangya Hospital Central South University	Sichuan	China
11	The Fifth People's Hospital of Suzhou	Suzhou	China
12	The Fifth People's Hospital of Wuxi	Wuxi	China